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31
Factory / Newtec Factory
« Last post by LamiyaJannat on May 31, 2021, 12:44:35 PM »
Newtec Pharmaceutical Ltd. was located with 2 acre land at Comilla Shodor, Boro Dhormopur (South Side), Bangladesh. This proposed site has been located in Comilla(South),Boro Dhormopur near Ratanpur Bazar.The total area of land 30,000s.ft(apx.). The Factory site has been located at a distance of 12km from South site of Comilla City.Which is located outside the residential area and outside of the surrounding area are, South-30ft wide Road,North-some trees & vacant land,East-vacant land,West-vacant land.The plant has been designed to ensure the appropriate environment control facilities with all modern approaches.Therefore,minimizes the possibility to hamper the vicinity.
32
Packaging Unit / Emerging Technologies in Packaging Automation for Pharmaceuticals
« Last post by LamiyaJannat on May 31, 2021, 12:42:52 PM »
Ensuring pharmaceutical safety goes beyond the supply chain.

More pharmaceutical manufacturers are investing in automation strategies to improve their operations and services. Nearly 50 percent of pharmaceutical and medical device companies have line automation integration underway and will be tracking overall equipment effectiveness (OEE), according to the 2017 report, “The Evolution of Automation,” produced by PMMI, the Association for Packaging and Processing Technologies.

Automation increases confidence in the line by reducing operator failures, which can cause downtime, providing greater quality control in a highly regulated industry. The growing market for small-batch pharmaceuticals and unit dose packaging continues to increase demand for such technologies. As automation becomes an ever-greater component of the pharmaceutical manufacturing process, the way employees interact with machines on the packaging line is changing as well. These changes will be visible in the technologies displayed at Healthcare Packaging EXPO, taking place October 14-17 at McCormick Place in Chicago.

The Rise of Small-Batch Production

Almost 90 percent of prescriptions in the United States are for generic drugs, but generics account for only 28 percent of pharmaceutical revenue.2 On the other side of the coin are high-value biosimilars, manufactured for smaller, specialized patient populations. Many pharmaceutical companies outsource packaging, but orders for small-batch specialty drugs do not always meet the volume requirements of contract packagers.

“Pharmaceutical companies are looking for automation for lower-volume products,” said Tim Brosnan, director of sales and business development at Medical Packaging Inc. “Automation allows you to serialize, calibrate, validate and test in a repeatable process, making it preferable from an FDA compliance standpoint.”

Medical Packaging is an equipment supplier developing automation technology to meet the needs of smaller manufacturers, allowing them to produce high-quality pharmaceuticals that make them competitive with larger companies. At Healthcare Packaging EXPO, booth W-1029, the company will showcase The FD-Pharma Unit-Dose Packaging System, an automated solution that offers built-in printing, pumping and barcoding for unit-dose oral medication at a speed of 34 cups per minute. The machine allows smaller pharmaceutical manufacturers to fit a full packaging line for small runs or clinical trials on just an 8-foot table, packing a robust operation into a small footprint.

Unit Dosing

Packaging compliance is changing, explains Brosnan, who has seen a recent pickup in requests for unit dose packaging — a method of single drug-dose delivery in barcoded, non-reusable containers. Hospitals demand unit dose packaging because they find it leads to fewer medication errors. It is also popular with patients who find the portability and small package sizes convenient. Additionally, unit dose packaging improves patient compliance. In many cases, old age or medical conditions make it difficult for patients to handle and administer medications correctly. User-friendly unit dose packaging prevents these mishaps. 

Another market driver is the recent U.S. Food and Drug Administration (FDA)-mandated compliance of unit dosing in clinical trials. Unit dose packaging offers cost-saving benefits because, with accountability for every pill, there are no leftovers or medication errors. As a result of this growing need, Kahle Automation (booth W-857) has seen a recent increase in demand for its custom-engineered unit dose pharmaceutical packaging solutions.

“Previously, drugs were packaged in vials for standard delivery,” said Julie Logothetis, president of Kahle Automation. “Pharmaceuticals are now put into pre-filled syringes with a significant amount of additional safety features, like reuse prevention, which our equipment handles.”

The Rise of Cobots

Robotic automation improves consistency of quality and flow because it eliminates the human error factor. For example, printers were installed manually on packaging lines in the past, leaving room for potential misalignment. Today, they are set up automatically. That is why cobots — collaborative robots — are especially valuable. In fact, the market for cobot technology grew 18 percent in 2017, with a growth forecast of 15 percent from 2018-2020.3  With cobot technology, people work alongside robots at one workstation, helping companies reap the benefits of automation while keeping humans part of the process.

“Automated systems, like our tube feeding system, eliminate many of the redundant tasks previously handled by humans,” said Mathias Ponzelar, vice president of sales at IWK Verpackungstechnik GmbH, an ATS Automation company (booth W-753). “While you used to have people removing each tray from the pallet, everything is now automated.”

IWK, a leading supplier of tube filling and cartoning technology for pharmaceuticals and cosmetics, develops solutions that present smaller footprints, greater flexibility and cost reductions with their cobot technology. 

Cobots reduce some of the environmental and spatial drawbacks of traditional robots. They reduce the floor space of packaging lines and are more suitable for small- and mid-scale packaging operations. These types of systems are becoming more common in today’s micro-batch pharmaceutical landscape. Cobots are also smarter than traditional robots, equipped with sensors, smart technologies linked to IT and Industry 4.0. Cobots can manage simple tasks that might cause repetitive stress injuries in humans. They can operate in temperatures that would be uncomfortable or intolerable to people and manipulate materials that may be unsafe for human handling, with the added benefit of having a human nearby to ensure everything goes smoothly.

An Evolving Workforce

As packaging automation for pharmaceuticals transforms, the roles of the humans who operate the machines are changing as well. The demand for technical workers and machine operators exceeds the available pool of skilled workers. Some companies are struggling to bring their workforce up to speed when handling the new machinery. That is why Pester USA (booth W-731) is focused on creating machines with easy-to-use human machine interface (HMI) systems.
“Pharmaceutical companies are seeking an effective way to automate and reach increasing production targets but with an as simple and user-friendly system as possible,” said Ryan Braun, vice president, sales and marketing at Pester USA. “We have redesigned our HMI to be more intuitive and allow users to operate with relative ease. For example, some HMI products offer functionalities that connect to certain smartphones.”
Pester plans to demonstrate its newest HMI system at Healthcare Packaging EXPO, allowing visitors to experience the interface firsthand.

Automation makes the pharmaceutical manufacturing processes manageable and consistent. It allows real-time data tracking of line metrics, making it easier for pharmaceutical companies to comply with the regulations around serialization of their products. Innovations in cobot and HMI technology are changing the way humans and machines work together in the pharmaceutical manufacturing industry.

Source: packagingstrategies
33
Warehouse / Smart Warehouses: Automating Transport in Pharmaceutical Manufacturing and Suppl
« Last post by LamiyaJannat on May 31, 2021, 12:38:00 PM »
Automation systems, vehicles, and robots improve efficiency of transporting materials and finished goods in pharmaceutical warehouses.

Self-driving vehicles and robots that pull items from shelves and deliver them to another location in a manufacturing facility or warehouse are not just science fiction anymore-these technologies and others are already being used for automated movement of materials and finished goods in various industries, including the pharmaceutical industry. Efficiency is a primary driving force for this type of automation, which increases accuracy and reduces labor costs.

In the pharma manufacturing “facility of the future”-and in some facilities already today-automated systems will move raw materials or semi-finished goods from the warehouse to the production line or between departments, and they may also move finished goods from the line to the warehouse. Autonomous mobile robots (AMRs) have an intelligent navigation system with built-in sensors, cameras, and software that allows them to “identify their surroundings and take the most efficient route to their destinations, safely avoiding obstacles and people,” says Ed Mullen, vice-president of sales for North America at Denmark-based Mobile Industrial Robots (MiR). These collaborative robots can improve productivity and efficiency, and return on investment is typically less than a year, says Mullen.

Transporting goods in and out of cleanrooms with AMRs offers time savings, because employees have to change gowning when moving in and out of cleanrooms. Transporting materials from the warehouse to production departments using AMRs also becomes more efficient. AMRs allow “warehouse employees to stage materials, load the robot with material for multiple departments, and send it on missions to deliver the material automatically in real time,” explains Mullen. Automated guided vehicles (AGVs) can similarly be used for transport and may run faster, but these require physically mounted guides, such as magnetic stripes or rails, and so are not as flexible for facility layouts that may change, he adds. “The trend to collaborative automation in warehouses as well as production was in its very early stage five years ago, but because of technology innovations, it is booming now. We will see an even greater tendency to use collaborative robots in the coming years,” predicts Mullen. “Warehouse automation is an obvious target for cost savings, and we see that more companies request mobile robots like ours because they can take over the internal transportation, and skilled employees can be redeployed for more valuable tasks than just moving parts from A to B.”

Automating a warehouse

In warehouses for finished pharmaceutical goods, putaway and retrieval, as well as functions such as case picking, can be automated. Technologies available include storage/retrieval machines (S/RMs), which replace work conventionally done by standard fork-trucks, and gantry or articulating-arm robots for case picking activities, which are generally combined with conveyance and sortation equipment, explains Dan Labell, president of Westfalia Technologies.

If a company wants to consider automation, they should first evaluate the business case, considering labor savings goals, worker safety, and regulatory compliance, notes Jeff Christensen, vice-president of product at Seegrid. Automating the putaway process can be a first step towards a “smart” warehouse. “Companies can set up a pilot program that includes self-driving pallet trucks that replace manual forklift moves from dock to storage,” suggests Christensen. “Companies can also tie in small bin automated storage systems that carry items along conveyor belts from the sorting area to picking. Once these applications are tested, companies can expand their automation footprint by integrating software systems and increasing the number of self-driving vehicles on site.”

Sophisticated warehouse management systems (WMS) support the movement towards more fully automated warehouses. For warehouses of finished pharmaceutical goods, such as those delivering to pharmacies and hospitals, the near future will see “more emphasis on software integrations to connect data across systems, manage inventory, and improve performance. These systems will include the WMS and software associated with smart machines, such as self-driving vehicles,” predicts Christensen.

Cost-savings and better data tracking justify automation


Automation can be justified for high-volume products, but it can also make sense for lower case volumes of high-value products with special cold-storage conditions (e.g., blood plasma), notes Labell. In general, warehouses have been densified to enable growth and reduce construction costs, and the savings in real estate and construction can often pay for a majority of the automation costs, he adds.

Automated movement in warehouses of finished pharmaceutical goods will be needed to better track product and product serialization/lots and capture this information for everything leaving the pharma warehouse, says Brian Hudock, vice-president at Tompkins International. “The ability to scan product at the sellable level through multiple tracking devices and 100% data capture is important,” he adds.

Another driver for automation is the need to efficiently handle smaller shipments to support digital shipments. So far, says Hudock, US pharma companies have taken a limited approach to automation and have instead used third-party logistics (3PL) partners to handle distribution of smaller orders, such as those going directly to physicians, clinics, or home care. “Because most 3PL’s want longer contracts to invest in automation, the result has been mechanization for efficiency at best. The US distribution market, however, is on the verge of a major evolution as digital disruptors are entering the equation and are about to create a new channel in the form of increased direct-to-patient/home-care provider shipments,” predicts Hudock. He anticipates that Amazon and others will create changes in the supply chain that will justify automation at both manufacturers and 3PL partners.


Source: pharmtech
34
Vector-Borne Disease / Vector-Borne & Zoonotic Disease
« Last post by LamiyaJannat on May 31, 2021, 12:32:57 PM »
Vector-borne and zoonotic diseases (VBZD) are infectious diseases whose transmission involves animal hosts or vectors.
Vector-borne diseases are infections transmitted (spread) through the bite of infected blood-feeding arthropods (vectors) such as mosquitoes, ticks, and fleas. Vectors can carry infectious pathogens (germs) such as bacteria, viruses, and parasites that upon transmission become the causative agents of common diseases such as Lyme, Anaplasmosis, Babesiosis, Ehrlichiosis, West Nile Fever, Zika, Dengue, and Malaria.

Zoonotic diseases or zoonoses, such as Avian Flu and Rabies, are diseases that can be transmitted from animals to humans by either contact with the animals or through vectors that carry zoonotic pathogens to from animals to humans. Zoonotic diseases are caused by harmful germs like viruses, bacterial, parasites, and fungi. These germs can cause many different types of illnesses in people and animals ranging from mild to serious illness and even death. Some animals can appear healthy even when they are carrying germs that can make people sick.

How do germs spread between animals and people?

Because of the close connection between people and animals, it’s important to be aware of the common ways people can get infected with germs that can cause zoonotic diseases. These can include:

•   Direct contact: Coming into contact with the saliva, blood, urine, mucous, feces, or other body fluids of an infected animal. Examples include petting or touching animals, and bites or scratches.

•   Indirect contact: Coming into contact with areas where animals live and roam, or objects or surfaces that have been contaminated with germs. Examples include aquarium tank water, pet habitats, chicken coops, plants, and soil, as well as pet food and water dishes.

•   Vector-borne: Being bitten by a tick, or an insect like a mosquito or a flea.

•   Foodborne: Each year, 1 in 6 Americans get sick from eating contaminated food. Eating or drinking something unsafe (such as unpasteurized milk, undercooked meat or eggs, or raw fruits and vegetables that are contaminated with feces from an infected animal).

Source: nvhd.org
35
Antimicrobial Resistance / What is Antimicrobial Resistance (AMR)?
« Last post by LamiyaJannat on May 31, 2021, 12:24:21 PM »
What are antimicrobials?

Antimicrobials are drugs used to treat infections in humans and animals. Antimicrobials work by killing micro-organisms (bacteria, fungi, viruses, etc.) or stopping the growth of micro-organisms that cause infections. Antimicrobials include medicines such as antibiotics, antifungals and antivirals which are essential in protecting human and animal health, as well as animal welfare.


What is antimicrobial resistance (AMR)? 
         
Antimicrobial resistance (AMR) occurs when micro-organisms that cause infections adapt and prevent an antimicrobial from working against it. As a result, the antimicrobials used to treat infections are no longer effective, limiting the treatment options available and therefore making the most common infections more difficult to treat.
The terms antimicrobials and antibiotics are used interchangeably but generally when talking about AMR we are referring to bacterial resistance to antibiotics.

Why is antimicrobial resistance (AMR) an issue?


It is unlikely that there will be any new classes of antibiotics available for many years. This poses a serious threat to disease control throughout the world. This is not only a global public health concern but it will also have consequences for animal health, food security and the environment.

The discovery of antibiotics has revolutionized health care and prolonged life expectancy across the globe. Antibiotics have substantially reduced mortality from infectious diseases and have provided protection against infectious complications for many modern medical practices including surgery, neonatal care and cancer treatment.


Antibiotics are also widely used in animal health. The availability and use of antibiotics is of vital importance in protecting animal health and welfare, productivity and facilitating the production of safe, nutritious food. If antibiotics lose their efficacy there will be a lack of suitable medicines that farmers can avail of to protect animal health and welfare. This will impact on farm productivity and profitability.

How does antimicrobial resistance (AMR) develop and spread?


The development of resistance is a natural phenomenon that will inevitably occur when antibiotics are used to treat infection. Every time antibiotics are used; bacteria are offered the opportunity to develop resistance.
Resistant bacteria can be transmitted between animals, humans and the environment so AMR is a problem for both animals and, more importantly, humans.


In farming, animals treated with antibiotics can become potential sources of AMR. Resistant bacteria and antibiotic residues can be transmitted from these animals through animal manure spread across the land as fertilizer. This animal manure can be absorbed by food crops, thereby spreading resistant bacteria and antibiotic residues to humans through food. Large quantities of bacteria and antibiotic residues can also enter soil and groundwater from excreted animal urine and manure. Resistant bacteria can also be spread to humans through direct contact with animals.

What factors increase the development and spread of AMR?

The problem at present is that the continued use, particularly the inappropriate use of antibiotics in humans, animals and in other situations is leading to significant increases in the development and spread of AMR.

The misuse of antibiotics may lead to the development and spread of AMR, for example:

•   Overuse of antibiotics
•   Under-dosing with antibiotics
•   Not finishing the treatment course
•   Incorrect disposal of antibiotics
•   Use of high-spec broad spectrum antibiotic when a narrow spectrum more basic antibiotic will suffice
•   Blanket use of antibiotics in an untargeted manner
•   Treatment of bacteria that are not susceptible to the particular antibiotic
•   Treatment of diseases caused by viruses or other germs not susceptible to antibiotics


What can be done at farm level to prevent AMR?

When it comes to animal health, prevention is better than cure. The first step farmers can take to prevent the development of AMR is to improve the overall health status of the animals on the farm. This will not only reduce antibiotic use on farm but it will also maximize farm productivity. This can be achieved through disease prevention strategies such as good biosecurity measures, adequate housing, optimal stocking densities, vaccination and parasite control. Under no circumstances should antibiotics be used to compensate for poor farm management practices.
Antibiotics should be used to maintain animal health and welfare where necessary, in other words they should be used prudently.

To use antibiotics prudently is to use them correctly. The six R’s should be followed when using antibiotics:

1.   Right Veterinary Diagnosis
2.   Right Animal
3.   Right Antibiotic
4.   Right Dose
5.   Right Duration
6.   Right Storage and Duration
 
Source: teagasc
36
Premix / Manufacturing A Quality Premix
« Last post by LamiyaJannat on May 31, 2021, 12:17:21 PM »
A premix is a mixture of vitamins, trace minerals, medicaments, feed supplements and diluents. It is a value added solution for feeds with sustainable safety and quality. The premix industry is charged with the responsibility of manufacturing a high quality premix consistently, efficiently and economically.

Its main objective is to deliver the micro ingredients in a manner desired by the consumer. Premixing has progressed from the simple hand mixing of several ingredients to mechanical mixing, to continuous mixing, and now to computer controlled mixing. However, the basic concept of mixing ingredients together to result in a homogeneous blend has remained unchanged.
 
The principles of quality management can be applied to improve and sustain the quality of premix. Modern quality management has three interrelated elements i.e. quality design, quality control and quality improvement.

A quality premix can be manufactured only through a stringent quality assurance programme and current good manufacturing practices (cGMP).

Quality assurance is a proactive, continuous system for monitoring reproducibility and reliability of a product. It encompasses all the activities undertaken to ensure predetermined standards of a quality premix. Good manufacturing practices covers all the areas of the production process like personnel, facilities, raw materials, quality assurance checks, inventory control, processing, mixing, packaging and delivery.
 
Some premix plants are designed for specific functions, such as making poultry premix exclusively; others are designed for producing a variety of premixes for other segments as well. Regardless of the specific purpose of a premix plant, material flow follows a basic pattern.

Premix manufacturing process comprises:

A.     Raw Materials
1.   Selection & Specifications
2.   Purchase
3.   Receipt & Storage
4.   Sampling & Analysis
5.   Processing
B.     Formulation
C.   Weighing
D.   Mixing
E.   Packaging
F.   Labeling
G.   Storage of Finished Premix

A: RAW MATERIALS

1: Selection & Specifications

Vitamins and trace minerals are available in different forms and their bioavailability varies between sources. Amongst vitamins the stability forms an important criteria whilst bioavailabilty, potency and reactivity of trace minerals aid in their selection process. The form of ingredient selected must also be easily available, of economic interest and also impart acceptable physical attributes to the premix. In order to maintain the stability of vitamins throughout their shelf life it is recommended to procure more stable derivatives like coated forms, that are not destroyed even when mixed with trace minerals. The spray-dried form of vitamins improves the flowability of the premix. The list of nutrients with their recommended sources is shown in Table 1.

The specifications for all raw materials should be based on recommendations applicable for particular animal's feed as mentioned by AAFCO, AOAC, AFMA, I.P, U.S.P., etc.

2. Purchase of Raw Materials

Raw materials must be procured from approved vendors and should conform to the specifications laid down by the nutritionist. No material should be received without a certificate of analysis. Purchases should be done periodically taking care that sufficient inventory is maintained at all times. A purchase plan is desirable in accordance with production requirement.
 
3. Receipt & Storage of Raw Materials

The receiver should have enough information from the quality assurance program to be able to recognize the quality of product. Sacked ingredients should be checked for identification and condition. A reference number should be allotted for each raw material received into the premises. The sacked ingredients must then bear this reference number. Large consignments are to be weighed at weigh bridge whereas small ones by using electronic balance. The complete details of the raw material along with its reference number must be entered into the stock records.

The raw materials should be logged in after segregation of drugs and other nutrients. Extra care must be taken for labeling. Bags or containers must be stored in a dry location on pallets assigned to them taking care of sufficient space between the pallets for comfort loading and unloading.

To prevent development of stacking resistance not more than 10 bags are to be stored on one pallet. Meanwhile stacked stocks should be rotated to minimize lump formation, product degradation, and insect infestation. The storage area must have sufficient protection from rodents and insects. It should be well ventilated, sanitized and away from direct sunlight. Depending on the stability of raw material they must be stored in environment of controlled temperature and humidity. The storage area for approved and rejected materials must be distinct in order to prevent any confusion.

4. Sampling & Analysis

Sampling of raw materials is performed following a quality assurance programme. To obtain a representative sample, sampling should be done from bottom, center and top layer of the bag using a sample probe. When large consignments of raw materials are received, it is advisable to mix the raw material in mixer and then analyze each mixed batch to make an accurate assessment. Instruments like H.P.L.C, flame photometer and spectrophotometer are used for analysis of raw materials to obtain accurate results. Raw materials should be analyzed using official methods by trained personnel.

Approved raw materials may be considered for formulation. If raw materials are differing in their particle size but other parameters are satisfactory then they should be considered for further processing like sieving, milling etc. When they are not meeting the pre-determined specifications in terms of potency or purity then they should be rejected.

5. Processing

Processing seeks to modify the physical properties of raw materials to meet the specifications of premix. Processing basically includes:

A.   Sieving
B.   Milling

Sieving is a primary process of removing foreign materials from raw materials as well as separating coarse ingredients. The operation can be carried out in equipments like vibratory or mechanical sifters. Care must be taken that the sifter is cleaned well before and after use to prevent any sort of contamination. The 'overs' obtained in the sieving process may then be ground.

A multimill can be used to reduce particle size to the desired screen analysis. Regular checks should be performed to detect wear of mill screen and blades. The sieved and milled material is then bagged, weighed, labeled and transferred to the warehouse area for storage.

B. FORMULATION

This is an important and critical step in manufacturing a premix. Qualified personnel possessing knowledge and expertise regarding micro ingredients and powder technology should formulate a premix.

The formulator has to consider source of ingredients based on their physical, chemical characteristics, bioavailability, their interactions when mixed, handling characteristics, and economic implications on the final product before any final conclusion is arrived at.

Physical Characteristics

Particles of uniform size, density and that of spherical shape blend well to form a homogenous mixture. The chance of segregation is thereby minimized. For example trace minerals available in the market are invariably found to be coarse in nature whereas the vitamins are normally fine powders. Achieving a homogenous mixing of these two ingredients would be difficult (sand and pebble effect). However, homogenous mixing can be achieved by processing the trace minerals to the desired particle size and improved flowability.

The flow ability of the ingredients plays a vital role while handling the powder i.e. before and after mixing. Poor flowability results in bridiging, caking and product loss in the transfer system. Conversely too fluid a product may cause flushing.

Chemical Characteristics

Potency of vitamins, trace minerals and medicaments need to be considered whilst formulating high quality premixes. Based on the customer's requirement the formulator has to include the micronutrients considering their analytical value so that desired amount can be delivered when mixed in the feed. No materials should be incorporated in the premix without analysis since under or over addition may have deleterious effect on the overall performance of the birds consuming the feed.

Selection of carrier and its percentage is important for formulating a quality premix. It is generally preferable to leave sufficient space for a carrier in order to minimize any sort of interactions between the active ingredients. The carrier should serve the functions as depicted below:

•   It should neutralize the electrostatic charges present in certain ingredients.
•   Chemically inert
•   Primarily have the density, particle shape and particle size compatible with other micro ingredients so as to prevent any demixing in the premix.
•   Water sequester from other raw materials thereby reducing water activity and improve stability of the premix.
•   Impart good flowability. Types of carrier widely used in the formulation of premix:

A.   Organic carriers
B.   Inorganic carriers

Better premixes can often be prepared by employing a blend of predetermined ratio of several diluents rather than with just one. The organic carrier absorbs moisture while inorganic carrier contributes towards density of premix.

The formulator has to consider all the above - mentioned parameters whilst preparing the batch control or manufacturing record. The batch manufacturing record serves as a link between the formulator and actual production. While preparing the batch sheet the formulator has to give importance for the following details:

•   Nutrient requirements
•   Selection of ingredients
•   Potency of ingredient
•   Process loss
•   Level of free flowing agents
•   Level of antioxidant
•   Percentage of carrier
•   Packing & packaging material
•   Inventory of materials

The manufacturing of a premix should follow the batch control sheet under the supervision of trained personnel. The batch sheet should comprise following details:

•   Name of the premix
•   Code of premix
•   Production date
•   Batch no. of premix
•   Batch size
•   List of ingredients to be mixed
•   Batch no. of ingredients to be mixed
•   Mixing order of ingredients
•   Actual quantity of ingredients to be taken
•   Mixer name and mixing time
•   Instructions regarding packing and mixing
•   Provision for signatures

All the above-mentioned details aid in keeping a track of the premix which may be traced in future with respect to customer complaints or product recall. Thus it serves as a control copy.

C. WEIGHING

Weighing is an important point in manufacturing of a premix. No matter how good the formula is, it is difficult to achieve the desired nutrient levels in the premix without precise weighing. Any extra addition of vitamins may not improve performance but costs extra money, whereas lower levels could depress performance. Precision in weighing is critical for certain ingredients like Selenium, and Roxarsone where mistakes may even prove toxic.

The accuracy of the weighing balance enables precise weighing. The accuracy decreases with increasing size of the scale. As a general rule, a scale is accurate to no more than 0.1% of its total capacity. There is large variation in doses of different micro ingredients added in the premix. So weighing balances need to be sized according to their use as depicted left.

Assurance in weighing can be achieved by calibrating balances against standard weights. The balances should be preferably calibrated daily in the beginning of weighing and documented accordingly. They should be cleaned before and after use and must be subjected for maintenance twice a year.

D. MIXING

The mixing process is the heart of any premix-manufacturing unit. In a premix the proportion of ingredients vary considerably; hence in order to obtain a homogenous blend the mixing operation should be divided into two steps, A) Micro mixing and B) Macro mixing

A.   Micro mixing, as the name suggests, is for mixing micro ingredients which weigh less than one percent of mixer capacity. These ingredients should be initially mixed in a smaller capacity mixer like double cone blender. The micro mix so obtained should be then mixed in the large mixer with all other ingredients.

B.   Macro mixing is the actual blending of all components of the premix along with carriers in a batch mixer. The content uniformity of the premix is based on following parameters:

i.   Type of Mixer
ii.   Mixing Time
iii.   Mixing order

(i) Type of mixer
A mixer selected must be able to provide homogenous mixtures of physically adverse particles incorporated at various levels in the mix. Horizontal or vertical mixers can be used. It must meet safety standards and must be properly installed. The requirements of a mixer are:

•   Affords good homogeneity with the component included at lowest possible content.
•   Short mixing time
•   Variable degree of filling, with no loss of mixing efficiency.
•   Complete emptying
•   Easy Cleaning
•   Provision for adding liquids
•   Absence of heat during mixing
•   Provision to break the lumps
•   Less consumption of energy
•   Least maintenance cost
•   Cost effective

A normal feed mixer is not recommended for premixes. A specialized mixer capable of mixing to a low CV (Coefficient of variation) is the most desired. Specialized Nauta mixers are normally capable of ensuring homogenous mixing. Examples of mixers: ribbon mixer, conical screw mixer, mass mixer, and cylindrical plough mixer etc.

(ii) Mixing time
The mixing time is also crucial for obtaining a homogenous premix. It is evident that shorter mixing time leads to under mixing while prolonged mixing time results in demixing. By trial and error and also by conducting coefficient of variation studies, optimum-mixing time can be arrived for a particular mixer.

(iii) Mixing order
The sequence of addition of various ingredients while loading the mixer can affect the quality of premix. If proper mixer loading sequence is not followed, oil balls, chemical interactions and particle segregation can result in a premix.

Regular mixer evaluation should be accomplished by conducting coefficient of variation studies. C.V value of less than 5% is indicative of excellent mixing. The mean assay value for the tracer should also be within the permissible limits of analytical variation. Any deviation from the expected result indicates any one of the following:

•   Improper mixing time
•   Irregular mixing order
•   Selection of bad mixer
•   Improper alignment of mixing aids
•   Wear out of internal part
•   Larger analytical variations

indicative of poor lab analysis Lack of uniformity in a premix is compounded when mixed into finished feed (multiplier effect). Hence utmost care has to be taken whilst manufacturing a premix.

E. PACKAGING

The primary purpose of packaging for premix is to maintain the stability of micronutrients and to protect the integrity of the premix. Improperly packaged premixes experience considerable loss in the potency of various sensitive ingredients. Selection or designing of packaging material should be according to the local climatic conditions. It should bear following properties:
•   Provides barrier against light, moisture, oxygen
•   No chemical interactions with the premix
•   Provides good printing surface
•   Sturdy enough to withstand the transport pressure.

The different types of packaging materials that could be use are glass containers, aluminium foil, paper and plastics. Ideally, aluminium foil lined multilayered paper bags provides an excellent barrier against light, moisture, oxygen, odour and flavour. Hence for very sensitive ingredients and where cost is not a constraint, aluminium foil package is the material of choice.

F. LABELING

Labeling of premix serves two purposes:

•   Provides complete information about the premix
•   Gives an identity to the premix and helps in differentiating from other premixes. The premixes for different segments like layer, broiler, breeder and dairy should bear labels of different colour. This prevents any confusion and mix-ups between the premixes.

A premix label should have following information:

•   Name of the premix
•   Composition
•   Dosage of premix
•   Net weight of premix contained in the package (in kg)
•   Regulatory/Statuatory statements.
•   Date of manufacture in month/year
•   Date of expiry in month/year
•   Batch number
•   Storage conditions
•   Directions for use
•   Name and address of the manufacturer with logo
•   Disclaimer note if any

Careful attention must be paid while preparing label since the customer follows the instructions given on the label. Any mistake made will be carried on to the feed and ultimately affect the performance of the birds.


G. STORAGE

The quality of premix is also affected by the storage conditions in the premises until it is transported through distribution channels. The following steps are recommended during warehouse storage:

•   The temperature and humidity of warehouse should be controlled below critical levels.
•   Keep the area clean, well lit and ventilated with fresh air.
•   Store the premix on the pallet meant for it taking care not to store more than 10 bags on each pallet.
•   Design the storage areas to facilitate the FIFO (First in First Out) policy, with bags stored in consecutive order so that oldest can be withdrawn first.
•   Make separate provision for storing sale return or expired premix
•   Keep floors, walls and walkways clean, dry and free of any obstructions.
•   Place sinks and bathrooms away from premix storage area.
•   Keep the area free from pests and rodents
•   No bag should be stored without any label.

When stored under such conditions the consumer is guaranteed of its label claim.

METHODS OF QUALITY CONTROL

1.   For raw materials
2.   For production process
3.   For finished premix

1. The raw materials must be analysed first and only then incorporated in the premix once it meets all the specifications. The formulator must be strict while considering the nutrient percentage in the raw material. Proper segregation must be done for the approved and rejected materials. Care should be exercised while actually taking the material for production. The raw material must be sieved to omit any foreign and oversized material, if necessary process before use.

2. The Premix production process ensures the precise weighing & inclusion of each required micro-ingredient in the premix. This method must be fool proof and verifiable through a system of physical (weight) and book (record) checks.

A preinclusion check should be performed by quality assurance personnel whereby random check is made for the number of bags, quality of material, their weights, cleanliness of mixer, integrity of packaging material and labeling. If any deviation is observed corrective steps should be taken immediately so that the error is not carried on to the final product.

A post manufacturing check is necessary to assure that premix manufactured is free of lumps and freely flowable.

Cross contamination should be eliminated while manufacturing quality premix. It becomes a matter of concern when drugs get carried over from one premix to another that is meant for another segment and where the contaminated drug is toxic to other species. There are three main methods that can reduce cross contamination in premix:

a.   Flushing- This is a technique whereby an ingredient such as ground grain or any carrier material is run through the system after a batch of medicated premix is produced. This ingredient will pick up much of the contamination in the system and then must be bagged up and used later when premix containing the same medicament is made.

b.   Sequencing-This technique involves the production of feeds containing the same medication at the same time. This reduces the number of times contamination may occur. A run of the medicated premix would then be followed by production of type of premix that would not be affected by a low level of a contamination.

c.   Mixer cleanout procedures-The mixer must be cleaned thoroughly before and after use with brush and compressed air. A thorough washout programme must be performed at least once a week. Care should be taken to ensure that the mixer is clean and dry before use.

3. The quality of finished premix is assured by analysing the same in the laboratory .The premix must be analysed for physico-chemical properties. The premix should be dispatched only if all the parameters are satisfactory. It may be difficult to analyse each and every batch manufactured for complete analysis and hence a sampling plan must be designed mentioning the analysis frequency of such premixes.

Premix is a critical input in feeds. The use of a quality premix is an important feature in any livestock operation leading to improved safety, reliability and performance. The production of quality premix thus deserves careful and professional attention. Product quality must be built into and not merely tested in, the product.

Monitoring of all the critical points affecting the quality of premix is the best solution for minimizing the deviations from standards. It is only through well organized, adequately staffed and accurately performed process and formulation controls that a desired quality of the premix may be achieved.

Source: The Poultry Site
37
Premix / What is premix and why does it matter?
« Last post by LamiyaJannat on May 31, 2021, 12:08:44 PM »
A premix is a complex mix of vitamins, minerals, trace elements and other nutritional additives (average of 25 raw materials) to incorporate in feed.

What is premix and why does it matter?

When it comes right down to it, anyone can mix some raw ingredients, package them and call this a product. So, how can animal feeds be differentiated? What makes one feed better than another, and why might animals perform so much better on one product versus another?

One of the things that sets feed products apart, influences animal performance, and addresses the specific nutritional needs of those animals is the premix used to create a finished feed product. All premixes are not created equal. The right formula will have a specific blend of vitamins, minerals, trace elements and nutritional additives.

Premixes make up a small percentage of the formulation but have the potential to make a big difference in the efficacy of a feed. Micro premixes are mixed into the feed between 0.2 and 2% of the total mix, while macro premixes make up between 2% to 8% of the mix (including also macro-elements, salts, buffer and amino acids).

These products provide a powerful component of the feed that ensures balanced, correct nutrition and value-added ingredients.

How can premixes be customized?

The Wisium premixes are formulated to specifically answer the nutritional needs of the animals being fed. These products are tailored according to local conditions and consider things like raw materials, sanitary conditions, specific targets, etc. The formulation approach and animal nutrition solutions are customized to meet the needs of each customer depending on their goals, species, and operating practices.

How can premixes add value?

The premix package in any animal feed delivers a variety of things depending on the type of animal being fed and end goals for the producer. Based on these factors, ingredients in this kind of product can differ greatly from one product to another. No matter what species or specifics the feed is designed for, a premix offers a vehicle to bring added value to the entire ration in an effective and efficient way.

The inclusion of chelated minerals, the addition of mycotoxins binders, or the use of specific flavorings are just a few examples of ways premixes can add value to the feed and create a better overall product. This kind of products offers nutrition that is delivered in a precise and correct way to better serve the animals and help them get the most out of their feed.

Source: wisium
38
Sulfa Group / Sulfonamides and Potentiated Sulfonamides
« Last post by LamiyaJannat on May 31, 2021, 12:00:17 PM »
The sulfonamides are one of the oldest groups of antimicrobial compounds still in use today. Sulfanilamide, an amide of sulfanilic acid, was the first sulfonamide used clinically. It was derived from the azo dye Prontosil. Other sulfonamides also share the same structure and the “sulfonamide” structure is prevalent among other drug classes, including nonsteroidal anti-inflammatory drugs (NSAIDs), anticonvulsants, and diuretics. Sulfonamide antimicrobials have been in clinical use for 50 years, but resistance is common when these drugs are used alone (without addition of trimethoprim or ormetoprim).

Clinical use of sulfonamides in dogs, cats, horses, and some exotic and zoo animals usually rely on the addition of trimethoprim (trimethoprim–sulfonamide) or ormetoprim (e.g., ormetoprim–sulfamethazine) to broaden the spectrum and increase antibacterial activity against bacteria that are resistant to either drug used alone. Technically, trimethoprim and ormetoprim are chemically called diaminopyrimidines, but they will be referred to by their respective names in this chapter. In companion animals, trimethoprim–sulfonamide combinations have all but replaced single or combination sulfonamide (triple-sulfas) treatment regimens. Sulfonamide administration is restricted in food animals, particularly dairy cattle, because of a concern for drug residues.

Pharmacology of Sulfonamides

All sulfonamides are derivatives of sulfanilamide (structurally similar to para-aminobenzoic acid), which was, in the 1940s, the first sulfonamide discovered to have antimicrobial activity. Note that in some countries and certain formularies outside the United States, different spellings have been used for sulfonamides (e.g., sulphamethoxazole for sulfamethoxazole; sulphadiazine for sulfadiazine; sulphadimethoxine for sulfadimethoxine, and so forth).
Many structural derivatives of sulfanilamide with differing pharmacokinetic and antimicrobial spectrums have been used in veterinary medicine to treat microbial infections of the respiratory, urinary, gastrointestinal, and central nervous systems.

Susceptible organisms include many bacteria, coccidia, chlamydia, and protozoal organisms, including Toxoplasma spp.
Sulfonamides are white crystalline powders that are weak organic acids, with solubility in water that varies among the specific drugs (ranging from slightly soluble to practically insoluble), and have a wide range of pKa values. The pKa values of these compounds and their ionization are important because – among other properties – the antibacterial activity, solubility, and protein binding have been associated with the pKa value (Mengelers et al., 1997). Drugs with high pKa are less soluble and exhibit lower protein binding; drugs with low pKa tend to have higher protein binding. The sulfonamides all share a similar structure, which contains a –SO2 group linked to a benzene ring, and a para NH2– group on N-4. An attached pyrimidine ring may contain zero, one, or two methyl groups (sulfamethazine, sulfamerazine, and sulfadiazine, respectively), which may undergo hydroxylation during metabolism. The other major site of metabolism is acetylation of the para-NH2, which can vary among species (for example, dogs do not acetylate, which is discussed in Section Metabolism). Acetylated forms of the drug tend to be less soluble.

The pKa is the dissociation rate constant. For some drugs, more than one pKa value is listed because of variation among sources. For pKa values, all sulfonamides are weak acids; trimethoprim and ormetoprim are weak bases. Log P is the logarithm of the partition coefficient between an organic solvent (oil) and water. The higher the Log P, the more lipophilic is the drug. Some values are from Mengelers et al. (1997) and van Duijkeren et al. (1994a).

The sulfonamides exhibit large variation in the extent to which they bind to plasma proteins. In general, the plasma protein binding is higher than other antimicrobials (>70% in many animals), and ranges from 90% (sulfadimethoxine in some species) to as low as 50% (sulfamethazine in some species). In horses, the protein binding of trimethoprim was 20–30% and for sulfadiazine was 18–30% (Winther et al., 2011). Because they are weak acids, sulfonamides are more soluble in alkaline than in neutral or acidic pHs; water solubility is enhanced when the sulfonamides are formulated as sodium salts or when in solution in more alkaline environments. Some sulfonamide solutions have pHs between 9 and 10, prohibiting extravascular use. Because solubility is decreased in acidic pH, they may become particularly insoluble and crystallize in renal tubules when urine pH is low, especially when high doses are administered, or animals are dehydrated or acidemic. To minimize crystalluria, yet allow administration of high doses, they have been formulated in combination with other sulfonamides. Each sulfonamide in a mixture of sulfonamides exhibits its own solubility in solution (law of independent solubility); that is, sulfonamides do not significantly affect the solubility of each other, but the antimicrobial effect is additive; thus, the use of “triple-sulfas” (three sulfonamides formulated in solution together) allows increased efficacy without a significant increased risk of adverse effects (Bevill, 1988).

Mechanism of Action

Sulfonamides rely on the requirement of susceptible organisms to synthesize folic acid as a precursor of other important molecular molecules in the cell. Sulfonamides act as false substrates in the synthesis of folic acid. Trimethoprim and ormetoprim (diaminopyrimidines, discussed in Section Potentiated Sulfonamides) produce a synergistic effect when used together by inhibiting the enzyme dihydrofolate reductase.

Folic acid metabolism is presented in Figure 32.2. Para-aminobenzoic acid (PABA), pteridines, glutamic acid, and the enzyme dihydropterate synthase interact to form dihydropteroic acid, the immediate precursor to dihydrofolic acid. Dihydropteroic acid is enzymatically converted to dihydrofolic acid by dihydrofolate synthase, followed by another enzymatic conversion of dihydrofolic acid to tetrahydrofolic acid (THFA) via dihydrofolate reductase (DHFR). The combination of sulfonamides and trimethoprim inhibits formation of tetrahydrofolic acid at two steps. This action is synergistic and increases activity against organisms that could otherwise be resistant. Tetrahydrofolate is a coenzyme in a number of complex enzymatic reactions and also is a coenzyme in the synthesis of thymidylic acid (a nucleotide), which is a building block of DNA. Trimethoprim and sulfonamides are bacteriostatic by themselves; together, they can be bactericidal. Bacteria are more susceptible to this combination than to either drug when tested alone (White et al., 1981).

Sulfonamides provide a false substrate for para-aminobenzoic acid (PABA) inhibiting the synthesis to dihydropteroic acid, a precursor for synthesis to dihydro- and tetrahydrofolic acid. Trimethoprim inhibits the enzyme dihydrofolate reductase, an enzyme critical to the synthesis of tetrahydrofolic acid.

Trimethoprim–sulfonamides are formulated in a ratio of 1:5 (trimethoprim:sulfonamide). In the animal, it is usually cited that the optimum ratio to produce antibacterial activity is 1:20 (Bushby, 1980; van Duijkeren et al., 1994b). Testing for susceptibility using approved CLSI methods (CLSI, 2015) uses a ratio of 1:20 trimethoprim:sulfonamide. However, this ratio is often much lower in animals because the trimethoprim component is excreted faster than the sulfonamide and the optimum ratio may actually be much wider than the value of 1:20 cited in human medical references, and may be as low as 1:40.
Sulfonamide action is dependent on the chemical similarity with PABA. Therefore, sulfonamides act as a false substrate in this reaction and synthesis of THFA is inhibited. The sulfonamides are relatively safe to mammalian cells because mammals utilize dietary folate for the synthesis of dihydrofolic acid, and they do not require PABA. The enzyme dihydrofolate reductase of bacteria has a much higher affinity (50,000 to 60,000-fold, and in some references as high as 100,000-fold) for trimethoprim than mammalian dihydrofolate reductase.

The mechanism of action of sulfonamides on bacteria does not entirely explain the activity against protozoa. Sulfonamides may inhibit protozoal dihydrofolate synthetase. Protozoal dihydrofolate reductase also is susceptible to the action of trimethoprim, which may explain some of the effect to support the use of these drugs for protozoal infections (treatment of protozoa infections is discussed in Chapter 42).

Clinical Uses and Microbial Susceptibility

The spectrum of activity for the sulfonamides is broad, affecting gram-positive, gram-negative, and many protozoal organisms. Sulfonamides have been used clinically for approximately 50 years and many organisms once susceptible to the sulfonamides are now resistant. To increase the activity, most of the sulfonamides used in clinical practice are combinations with either trimethoprim or ormetoprim (diaminopyrimidines). These combinations (referred to in this chapter as trimethoprim–sulfonamides, but also referred to in clinical practice as trimethoprim–sulfa or simply abbreviated as TMP/SU) have increased the activity.

Administration of a single sulfonamide, or combination of sulfonamides, continues to be used in some livestock practices. In the United States, there are no approved formulations of trimethoprim–sulfonamides available for food animals, but trimethoprim–sulfadoxine is available in some countries.

The susceptibility/resistance patterns of sulfonamides and the trimethoprim–sulfamethoxazole combination against the most commonly encountered veterinary pathogens has been reported (van Duijkeren et al., 1994a, 1995; Bade et al., 2009; Winther et al., 2011). The activity of these agents has allowed for treatment of common respiratory infections, urinary tract and soft tissue infections, and intestinal infections (intestinal protozoa). Susceptible organisms include Arcanobacterium, Bacillus spp., E. rhusiopathiae, L. monocytogenes, Streptococcus spp., (Streptococcus equi subsp. zooepidemicus from horses), and protozoa (coccidia and Pneumocystis carinii).

The wild-type strains of following organisms are usually susceptible to the trimethoprim–sulfonamide (or ormetoprim–sulfonamide) combination: Pasteurella spp., Proteus spp., Salmonella spp., Histophilus (formerly Hemophilus), the protozoa Toxoplasma, and coccidia. Other bacteria that may be susceptible, but for which resistance can develop, include Staphylococcus spp., Corynebacterium, Nocardia asteroides, Stenotrophomonas maltophilia, and bacteria of the Enterobacteriaceae (Klebsiella, Proteus, Enterobacter, and Escherichia coli).

The organisms that are consistently resistant to trimethoprim–sulfonamide combinations include: Pseudomonas spp., Chlamydia spp., and Bacteriodes. One should cautiously interpret trimethoprim–sulfonamide susceptibility for Enterococcus spp. Although Enterococcus may appear susceptible to trimethoprim–sulfonamides using in vitro tests, it escapes the antifolate activity of the drug in vivo by its unique ability to incorporate preformed exogenous folates (Wisell et al., 2008). Sulfonamides alone are not active against Enterococcus spp. Clinical failures are reported despite in vitro susceptibility and microbiology laboratories should not report the susceptibilities of Enterococcus to trimethoprim–sulfonamides.

The activity of trimethoprim–sulfonamides against anaerobic bacteria can be variable. When measured in vitro, trimethoprim–sulfonamides have good activity against anaerobic bacteria (Indiveri and Hirsh, 1986), but clinical results are not as good (Dow, 1988) because thymidine and PABA (inhibitors of trimethoprim–sulfonamide activity) may be present in anaerobic infections.

Trimethoprim–sulfonamides have been used to treat infections caused by protozoa (including Toxoplasma gondii) and intestinal coccidia. Trimethoprim–sulfonamide combinations have also been used to treat equine protozoal myeloencephalitis (EPM) caused by Sarcocystis neurona.

Interactions Affecting Antimicrobial Activity

Components found in some tissue environments may inhibit trimethoprim–sulfonamide activity. For example, thymidine and PABA present in infected tissue – may interfere with activity. This has been demonstrated in tissue cages in horses. Ensink et al. (2005) showed an inability to eliminate the infection in an infected environment, despite in vitro sensitivity. They cited inhibitors – such as PABA and thymidine – present in abscessed and infected tissues that may inhibit the effects of these drugs. In another study in which trimethoprim–sulfadoxine was administered to cattle with infected tissue cages (Greko et al., 2002), it was shown that high levels of thymidine in the tissue cage fluid inhibited trimethoprim and compromised the ability to eradicate the infection.

Susceptibility Testing

For susceptibility testing, trimethoprim–sulfame- thoxazole (1:20 ratio of trimethoprim:sulfamethoxazole) should be used, even when trimethoprim–sulfadiazine is used for therapy (CLSI, 2013, 2015). There are no quality control (QC) ranges developed for trimethoprim–sulfadiazine, and tests using trimethoprim–sulfamethoxazole are expected to give equivalent results. Winther et al. (2011) showed that there were no significant differences observed between the minimal inhibitory concentration (MIC) of sulfadiazine and sulfamethoxazole for individual bacterial strains, confirming that sulfamethoxazole is an effective surrogate for susceptibility testing of sulfadiazine. The CLSI susceptibility testing standards state that Mueller–Hinton agar containing excessive amounts of thymidine or thymine can reverse the inhibitory effect of sulfonamides and of trimethoprim, which may result in false-resistant reports (CLSI, 2013). Susceptibility testing agar that is as thymidine free as possible should be used. The current CLSI interpretive categories (CLSI, 2015) do not provide veterinary-specific interpretations; therefore, the human breakpoint is used by laboratories to predict susceptibility. For Staphylococcus spp. and the Enterobacteriaceae the susceptible breakpoint is ≤2/38 (trimethoprim/sulfonamide) and for Streptococcus spp. the breakpoint is ≤0.5/9.5 (trimethoprim/sulfonamide).

Drug Resistance

Resistance by many bacterial and protozoal organisms has become widespread due to the extensive use of sulfonamides over many years (Huovinen, 2001). Resistance occurs via efflux pumps, failure to penetrate the organism, and changes in target enzymes. Resistance can be transferable. Chromosomal resistance tends to occur slowly and confers resistance via impaired drug penetration into the microbial cell, producing an insensitive dihydropteroate enzyme and an increased production of PABA. Plasmid-mediated resistance, the most commonly encountered form of sulfonamide resistance, occurs quickly and manifests itself via the impaired drug penetration mechanism in addition to producing sulfonamide-resistant dihydropteroate synthase enzymes. If an organism becomes resistant to one sulfonamide, it is generally resistant to all other sulfonamides. Resistance to trimethoprim occurs via overproduction of the dihydrofolate reductase enzyme or synthesis of an enzyme that resists binding of the drug.

Oral Absorption

In dogs, absorption is excellent and not affected by feeding (Sigel et al., 1981). There has been considerable interest in the oral absorption of trimethoprim–sulfonamide combinations in horses and the effect of feeding. When trimethoprim-sulfonamides are administered to a horse that has not been fed, rapid absorption occurs, but is not as complete as for dogs or people. Nevertheless, oral administration is sufficient in horses to produce effective results. The fraction absorbed for trimethoprim was reported to be 67%, and for sulfadiazine 58%, but for both components the variability was high (van Duijkeren et al., 1994c). Oral absorption in another study in horses was 90.2% for intragastric administration and 74.45% for the oral paste (Winther et al., 2011). For trimethoprim in the same study, it was 71.5% oral absorption for the intragastric administration and 46% for the oral paste (Winther et al., 2011). In that study the absorption of trimethoprim–sulfadiazine was likely diminished by feeding. When trimethoprim–sulfadiazine was administered to horses as an oral suspension and compared to the equine paste, the absorption from the suspension was higher for both drugs compared to the paste, that is 136% and 118% of the paste AUC concentrations for sulfadiazine and trimethoprim, respectively (McClure et al., 2015). In another study (van Duijkeren et al., 1994c) the oral paste was compared to two compounded formulations (mixed with syrup and water or carboxymethylcellulose gel). In this comparison, all three formulations were judged to be equivalent. When administered to horses that have been fed or when it is added to the horses’ feed concentrate, a delayed and biphasic absorption is observed (van Duijkeren et al., 2002, 1995). When trimethoprim sulfachlorpyridazine was administered to horses, oral absorption was delayed, with the first peak appearing 1 hour after dosing and the second appearing 8–10 hours postdosing. Dual absorption peaks were not found after nasogastric administration (van Duijkernen et al., 1995). The best explanation for this phenomenon is that that there is an initial peak of absorption in the small intestine where much of drug absorption is known to occur. However, the drug that is bound to feed (adsorption) is unavailable for absorption until it travels to the cecum and, after digestion of the carbohydrates, the drug is released, producing a delayed and biphasic peak in absorption. Trimethoprim–sulfachlorpyridazine can bind to equine cecal contents 60–90%, which supports the theory of the “double peak”. Feeding also decreased the systemic availability from 70% when fasted to 45% when fed (van Duijkernen et al., 1996).

In ruminants, age and diet can markedly affect trimethoprim and oral sulfadiazine disposition in calves (Guard et al., 1986; Shoaf et al., 1987). Orally administered sulfadiazine (30 mg/kg) was absorbed very slowly in those calves fed milk diets, with absorption slightly higher in ruminating calves. Trimethoprim was absorbed in preruminant calves, but not absorbed in mature ruminants after oral administration (Shoaf et al., 1987), probably because of inactivation in the rumen.
Sulfasalazine is not used for the antibacterial properties, but is used to treat inflammatory disease of the large intestine in small animals (discussed in more detail in Chapter 46). It is not absorbed as a whole molecule but rather is cleaved into two more active compounds by native resident colonic bacteria.

Distribution

Sulfonamides distribute to most body fluids, but are not distributed to tissues as extensively as trimethoprim. Generally, sulfonamide tissue concentrations are lower than plasma concentrations (approximately 20–30% of corresponding tissue concentration), but distribution to extracellular fluids is generally high enough to produce effective concentrations against susceptible pathogens. High protein binding affects the distribution and markedly increases the half-life of sulfonamides.
Sulfonamides are weak acids and trimethoprim is a weak base. The ionization affects distribution, which favors the distribution and ion trapping of trimethoprim in tissues (intracellular environment is typically more negative than plasma). Therefore, trimethoprim has a higher volume of distribution than sulfonamides. Also, because sulfonamides are weak acids, the pH-partition hypothesis shows that these drugs do not attain therapeutic concentrations in milk; however, enough passive diffusion occurs to limit their use in dairy cattle.
 
Source: veteriankey
39
Saline / Fluid Therapy and its Applications
« Last post by LamiyaJannat on May 31, 2021, 11:35:18 AM »
Fluid therapy is one of the most common therapies provided in small animal medicine. Patients are given fluids for many reasons, and the number of available fluids is growing. Knowing why fluids are ordered, the goals and limitations of fluid therapy, and how fluids are chosen is a key competency for veterinary technicians. This article reviews some of the reasons fluid therapy may be ordered for a patient, how to administer and monitor fluid therapy, and the fluid types available in the United States.

Body Water Compartments

To understand fluid therapy and its applications, one must first understand the distribution of fluid and water in the body. Total body water (TBW) comprises approximately 60% of a patient’s body weight.1 Approximately 67% of TBW is found inside the body’s cells and is referred to as intracellular fluid (ICF). The remaining 33% of TBW is the extracellular fluid (ECF), which is further divided as follows:

•   Interstitial fluid, which bathes cells and tissues (~24% of TBW)
•   Plasma, the liquid portion of blood, which constitutes most of intravascular volume (~8%–10% of TBW)
•   Transcellular fluid, which comprises synovial joint fluid, cerebrospinal fluid, bile, and the fluid in the linings of the peritoneal cavity, pericardium, and pleural space (~2% of TBW)

A helpful rule of thumb to simplify the distribution of fluids in the body is the 60:40:20 rule: 60% of a patient’s body weight is water, 40% of body weight is ICF, and 20% of body weight is ECF.1

The body is considered a closed system, meaning that any fluid lost must come from one of the compartments listed above. In the case of hemorrhage, for example, fluid is lost from the intravascular space (i.e., plasma) but also from the ICF in the cells lost (e.g., red blood cells, white blood cells). In addition to losses, fluid can and does move between compartments in a dynamic and ever-changing fashion. When providing fluid support to patients, technicians must keep in mind which compartment needs to be replenished or what derangement needs to be corrected. This knowledge helps guide both fluid choice and the method used to administer fluid therapy.

Reasons for Fluid Therapy

Veterinary professionals provide fluid therapy to patients for many reasons, including correction of dehydration, expansion and support of intravascular volume, correction of electrolyte disturbances, and encouragement of appropriate redistribution of fluids that may be in the wrong compartment (e.g., peritoneal effusion).2

BOX 1 Clinical Signs of Shock

•   Vasoconstriction
o   Pale mucous membranes
o   Prolonged capillary refill time
o   Peripheral temperature < core temperature
o   Reduced urine output
•   Decreased mentation
•   Tachycardia (cats may present with bradycardia)
•   Hypotension (poor pulse quality)
•   Reduced oxygen saturation (low SpO2)
•   Lactate >2 mmol/L
•   Metabolic acidosis

The first step in determining whether a patient needs fluid therapy is a full physical examination, including collection of a complete history. The veterinary staff must assess whether the patient is perfusing its tissues well, check for dehydration, and evaluate losses from any of the fluid compartments.3

Inadequate Perfusion

Patients that cannot adequately perfuse their tissues require immediate intervention with fluid therapy to restore perfusion and correct shock. Shock is defined as the critical imbalance between the delivery of oxygen and nutrients (carried by blood) to tissues and the tissues’ demand for these components. If allowed to persist, this imbalance can lead to acute decompensation and death. Restoring perfusion and, subsequently, oxygen and nutrient delivery to tissues is crucial to survival in these patients.1

Shock is a life-threatening emergency and must be recognized and treated immediately on presentation. Patients may present with several clinical signs (BOX 1), and owners may report a history of recent fluid loss, such as intractable vomiting, severe diarrhea, or hemorrhage. Once shock is recognized, access to the intravascular compartment must be achieved and fluid resuscitation initiated as soon as possible (see Ways to Provide Fluid Therapy), with the goal of restoring intravascular volume and flow, thus improving perfusion and delivery of oxygen and nutrients to starving tissues.

Oxygen delivery to the tissues (DO2) depends on cardiac output and arterial oxygen content. Cardiac output is the product of stroke volume and heart rate. Stroke volume is defined as the amount of blood ejected from the left ventricle during systole and is a product of preload (the amount of blood entering the heart), afterload (the amount of resistance in the vasculature to the flow of blood from the heart), and contractility (the heart’s ability to contract). Once perfusion and, by extension, DO2 is restored, homeostasis can be reestablished and the shock state will be remedied. Correction of perfusion deficits is demonstrated by normalization of the forward perfusion parameters, listed in BOX 2.1

BOX 2 Forward Perfusion Parameters

•   Heart rate
•   Pulse quality
•   Respiratory rate
•   Mucous membrane color
•   Capillary refill time
•   Mentation
•   Temperature and color of digits

Dehydration

Loss of fluid from the intracellular and interstitial compartments leads to dehydration. If severe, dehydration can be detected in derangements in forward perfusion parameters1 as well as by the tests listed below. Any patient determined to be more than 10% dehydrated is considered severely dehydrated4 and requires immediate fluid resuscitation and careful monitoring.5 Dehydration must not be confused with hypovolemia: dehydration describes a water deficit in the interstitial and intracellular compartments, whereas hypovolemia describes a loss of fluid in the intravascular space.4

Hydration status can be assessed using several simple tests. One of the easiest to perform is a skin tent test to check the turgor, or moisture level, of the skin. To perform this test, the skin over the thorax or lumbar region is pulled away from the back. In a well-hydrated animal, the skin immediately returns to its normal resting position. If the tent formed remains standing, it can be an indication of dehydration.1,5 When performing this test, veterinary technicians can often appreciate a “tacky” or “sticky” feeling in the underlying tissue, which is further evidence of dehydration. The skin tent test can be confounded by both emaciation (decreased turgor even if euhydrated) and obesity (increased turgor in the face of dehydration) and must be considered in relation to other parameters and physical examination findings. Age is another factor to consider: loss of skin turgor progresses with increasing age, and neonates exhibit very little skin tenting even when dehydrated.
Another way to check for dehydration is to feel for moistness on the mucous membranes. This is most easily accomplished by sliding a finger along a patient’s gum line or inside the cheeks. If the membranes themselves are dry or sticky, it may indicate dehydration. In the case of vomiting animals, it is necessary to differentiate excess saliva in the mouth from mucous membrane moisture.

In patients with normal kidney function, oliguria can indicate dehydration, and the small amount of urine produced will likely be concentrated (urine specific gravity [USG] >1.030).5 Other laboratory parameters that change with dehydration include packed cell volume and total protein (PCV/TP) levels, which demonstrate hemoconcentration (high PCV) and hyperproteinemia (high TP) in dehydrated patients5 due to the loss of the fluid portion of the blood as the body tries to maintain fluid balance and homeostasis. Serial measurements of both USG and PCV/TP can help the veterinary care team evaluate the effectiveness of fluid resuscitation efforts, as both levels should decrease as intravascular volume is restored and the interstitial fluid and ICF compartments are replenished.

Previous, Ongoing, and Anticipated Losses

Consideration of fluid losses is an important part of determining a fluid therapy plan. These losses may have occurred before presentation to the clinic—such as animals with a history of protracted vomiting or diarrhea—or may be anticipated after treatment has been instituted, as is often seen in cases of postobstructive diuresis in cats with urinary obstruction. These losses must be factored in when deciding the type, amount, and route of fluid therapy. When calculating fluid losses, veterinary technicians should include urination, defecation/diarrhea, vomiting, removal of effusions or gastric contents, fluid loss from drains, and insensible losses (such as from panting).

Ways to Provide Fluid Therapy

Even veterinary technicians who have been in practice for only a short while have likely seen fluids given several ways. Oral, subcutaneous, intravenous, intraosseous, and even intraperitoneal routes are all used, depending on the species receiving fluid therapy and why it is needed.

Oral Route

By far the simplest mode of fluid therapy, providing water per os can correct some conditions, including mild salt toxicity and mild cases of dehydration. Providing water via the oral route is as simple as offering the patient a bowl with a premeasured volume of water on a set schedule and measuring the amount consumed. However, in patients that have gastrointestinal pathology (i.e., parvovirus infection) or are unable to consume adequate amounts of water to maintain normal urine production or to establish and maintain fluid homeostasis, other means of fluid resuscitation must be used.

Subcutaneous Route

Subcutaneous fluids are a mainstay of veterinary therapy. Subcutaneous fluid administration is used for many disease conditions, including cases of mild vomiting and diarrhea or mild dehydration, or to support kidney function in animals with chronic kidney disease. It is relatively simple to provide fluids via the subcutaneous route, and many owners can be trained to provide this therapy at home, mitigating the need for hospitalization. As with other therapies given subcutaneously, it takes time for subcutaneous fluids to be absorbed into the bloodstream; thus the subcutaneous route is not appropriate to treat life-threatening conditions such as severe dehydration or shock.

Intravenous Route

IV fluid therapy is very common in veterinary practice and allows practitioners to restore intravascular volume, correct dehydration, and administer IV medications. IV catheter placement is a core nursing competency for veterinary technicians and allows for IV fluid therapy in emergency presentations and hospitalized patients alike. In addition, access to the vascular space allows for other therapies, including transfusions, medications, and parenteral nutrition.

In emergency situations or when a large volume of fluid is needed over a short amount of time, selecting a catheter with a large bore and a short length is preferable to allow for rapid infusion of fluids. This is a function of Poiseuille’s law, which governs the flow of fluid through a tube: essentially, the shorter the tube, the smoother the flow, and the larger the tube’s diameter, the faster the flow, meaning that large-bore, short catheters are the best choice when a large volume of fluid must be delivered quickly, such as in cases of hypovolemic shock.6,7 T-ports and additional tubing (e.g., extension sets) may decrease both the amount of fluid and the speed of delivery. In an emergency situation, it is best to minimize any extra IV accessories that might impede flow.

In addition to peripheral access, IV fluid therapy can be delivered through central line catheters. These catheters are longer than typical peripheral IV catheters and reach the central circulation via the vena cava. Central lines are commonly placed in the jugular vein, with the tip of the catheter sitting just outside the entrance to the right atrium to facilitate measurement of central venous pressures, if desired. Jugular central line catheters can be placed with a guidewire (i.e., Seldinger technique) or a peel-away introducer. They are available with multiple lumens to enable sampling, concurrent administration of incompatible fluids, and administration of hypertonic solutions that may cause phlebitis if given peripherally (e.g., dextrose concentrations >7.5%). The central circulation can also be reached with a long, through-the-needle catheter (e.g., Intracath) placed in either the lateral saphenous vein or the medial femoral vein or a peripherally inserted central catheter (PICC) in the same vessels. Because of their long length, smaller bore, and longer time usually required for placement, central catheters are not recommended for emergency fluid therapy, but can be maintained for long periods, making them well-suited to longer-term fluid therapy.

Intravenous Intraosseous Route

Intraosseus (IO) catheters are an excellent choice for providing drugs and fluids to patients in which IV access is difficult—if not impossible—to obtain in a timely fashion. Patients with severe hypotension or complete cardiovascular collapse (i.e., patients in cardiac arrest), that are severely dehydrated, or in which IV access is not obtainable (as in patients with edema, burns, thrombosis, or obesity) can benefit from placement of a catheter in the medullary cavity of a bone (IO). This route is also very useful in tiny patients, such as neonates and pocket pets (e.g., hamsters, gerbils). The materials are readily available in most, if not all, veterinary practices, and placement may mean the difference between life and death. The IO route is fast and has been proven8,9 to provide access to the central circulation comparable to the access provided by central venous catheterization, making it the first choice for administration of drugs and fluids when IV access cannot be achieved.
For all of the advantages of the IO route, there are several limitations. Fluid cannot be provided at a rate equivalent to that of IV access, and the needles are not designed for long-term use. Most sources1,2,4,7,10 recommend removal of IO access devices within 72 to 96 hours of placement to avoid the development of osteomyelitis or bone infections, as long as IV access can be obtained.

Monitoring

Veterinary technicians are responsible for providing therapies in as safe a manner as possible; this includes fluid therapy. Safety can be maintained with vigilant monitoring. To monitor a patient’s perfusion status, technicians should observe forward perfusion parameters (BOX 2). Normalization of these parameters is a good indication that fluid therapy is being provided successfully. In the laboratory, technicians can perform serial measurements of PCV/TP and USG. In patients that presented in a state of dehydration with increased PCV/TP, lowering of these values indicates a return to normal fluid levels in the intravascular space and an improvement in overall hydration. Increasingly dilute urine means that the patient’s kidneys have detected an increase in intravascular volume and a restoration of overall fluid balance.

One of the easiest and most sensitive ways to monitor fluid therapy in patients is with multiple weight checks throughout the course of therapy. Since TBW is 60% of a patient’s body weight, increases in any fluid compartment leads to a commensurate increase in the patient’s overall weight. However, an increase >10% from baseline admission weight should prompt an investigation of the possibility that the patient is becoming overhydrated, also known as becoming fluid overloaded.
Swelling of the conjunctiva without signs of inflammation or irritation is known as chemosis. This is a late sign of fluid overload; it is incumbent on veterinary technicians to recognize earlier signs such as increased respiratory rate and effort, increased breath sounds (e.g., crackles), or clear nasal discharge.

Fluid overload is a major complication of fluid therapy and can lead to pulmonary edema, ascites, and peripheral edema with the potential for development of compartment syndrome. A patient who becomes tachypneic, develops clear nasal discharge, or is found to have crackles on thoracic auscultation while receiving fluid therapy should be suspected of becoming overhydrated. If these signs are noted, particularly in combination with an increase in body weight, IV fluid therapy should be stopped and the veterinarian should be notified immediately.11 Chemosis (swelling of the conjunctiva) is a late sign of fluid overload and requires urgent treatment including cessation of IV fluids and potential administration of diuretic agents.

Fluid Types Available


Several types of fluids are available, ranging from crystalloids to synthetic colloids to natural colloids (i.e., blood products). Each type has its place in the treatment of various conditions and pathologies found in veterinary patients. It is easiest to differentiate fluids based on their purpose: maintenance or replacement therapy. The components of common maintenance and replacement fluids available to veterinary practitioners in the United States. The resources listed in the Recommended Reading box can provide more detailed explanations of fluid types and their effects.

Patients presented as an emergency often require immediate intravascular expansion in the form of crystalloid boluses, or large volumes of crystalloid fluids. Crystalloid fluids move quickly from the intravascular space into other fluid compartments, primarily the intracellular compartment. Less than one-third of the crystalloid volume administered intravenously persists in the vasculature 1 hour after administration,4 making these fluids an excellent choice for treating dehydration and electrolyte derangements and correcting free water deficits.

Crystalloid fluids can be categorized as follows:

•   Free water: 5% dextrose in sterile water or 0.45% saline. This hypotonic (i.e., containing fewer solutes than ICF) solution replenishes the interstitial fluid and ICF compartments.

•   Replacement solutions: These balanced, isotonic solutions are designed to replenish the ECF compartments, including increasing intravascular volume and restoring perfusion. Isotonic fluids contain a solute concentration that approximates that of ICF, and crystalloids that are considered “replacement” fluids have compositions that closely match the electrolyte balance and pH of ECF,1 making them ideal to replace losses from that fluid compartment (e.g., dehydration).

•   Maintenance solutions: These balanced, isotonic solutions have less sodium and more potassium than replacement fluids and may be more suitable for long-term fluid therapy after restoration of intravascular volume and correction of electrolyte derangements. Maintenance fluids are rarely used alone—they are usually combined with a ratio of 0.9% sodium chloride1 (aka “normal” or “isotonic” saline) to more closely match the composition of the fluid in the intravascular space, preventing unwanted fluid shifts between compartments.

•   Hypertonic solutions: 7% to 23.4% saline. These fluids contain a solute concentration higher than that of ICF and rapidly expand intravascular volume by drawing water from the interstitial and intracellular compartments. Because of this oncotic pull, hypertonic solutions should never be used in cases of severe dehydration.

Colloids

Many practitioners also use colloids (either synthetic or natural) in an emergency to expand the intravascular compartment without the risk of fluid overload posed by infusing large volumes of crystalloid fluids. Colloids contain large, osmotically active particles that work to hold fluid in the vasculature after administration.

Synthetic colloids are fluids with large molecules designed to provide oncotic pressure support within the intravascular space. Natural colloids are blood products such as whole blood, packed red blood cells (pRBCs), plasma, and albumin. Whole blood and pRBCs have the added benefit of providing oxygen-carrying capacity, helping to prevent and treat hypoxia.
The use of colloids is highly controversial in human medicine and becoming so in veterinary medicine as well,12 with recent research13 implicating a link between the use of a synthetic colloid and the development of acute kidney injury in dogs.

Developing and Implementing a Fluid Therapy Plan

There is a helpful guideline when it comes to fluid therapy: Replace like with like. This means if a patient has lost blood, that fluid should be replaced with plasma, pRBCs, or whole blood. If a patient has lost body fluids through diarrhea, vomiting, or excessive urination, replacement should be with similarly constituted isotonic crystalloid fluids. While development of the fluid plan is ultimately the veterinarian’s purview, it is important for veterinary nurses and technicians to understand the fluids available and for what conditions they might be used in clinical practice.

Fluid therapy in the veterinary hospital or clinic has 3 primary phases, which can overlap and alternate, depending on how a patient presents and the progression of its disease process. The resuscitation phase refers to correcting shock and other life-threatening fluid deficits; the replacement phase is the time taken to replace dehydration deficits; and the maintenance phase covers fluids provided during hospitalization to support and maintain homeostasis. BOX 3 provides examples of fluid choices in some specific disease processes.

BOX 3 Appropriate Fluid Choices for Selected Disease Processes

•   Cardiac disease: Low-dose maintenance crystalloid, such as 0.45% saline with dextrose (may require potassium and or magnesium supplementation)

•   Vomiting/diarrhea: Replacement crystalloid, such as lactated Ringer’s solution, Normosol-R, or
Plasmalyte-A

•   Diabetic ketoacidosis: Replacement crystalloid, such as lactated Ringer’s solution, Normosol-R,
Plasmalyte-A

•   Hemorrhage: Natural colloid, such as plasma, whole blood, pRBCs

The amount of fluid to be provided to a patient must be calculated carefully, taking into account the need for intravascular volume expansion, the profundity of perfusion deficits, the degree of dehydration, and the severity of electrolyte derangements, among other considerations. BOX 4 lists common fluid therapy calculation formulas.

BOX 4 Fluid Therapy Formulas

Calculation of Dehydration Deficit1
Body weight (kg) × % dehydration as a decimal = liters of fluid required to correct dehydration
Calculation of Maintenance Fluid Requirements*
Dogs: Body weight (kg)0.75 × 132 = 24-hour fluid requirement in milliliters
Cats: Body weight (kg)0.75 × 80 = 24-hour fluid requirement in milliliters
Ongoing losses (e.g., from diarrhea, vomiting, or polyuria) must be calculated and added to the total maintenance requirement obtained from these formulas.
*UC Davis School of Veterinary Medicine fluid therapy formula.
 

Source: todaysveterinarynurse
40
Eggshell Remover / Calcium and Phosphorus Deficiency in Poultry
« Last post by LamiyaJannat on May 31, 2021, 11:18:25 AM »
Both calcium and phosphorus are required for the synthesis of bone. These elements also play an important role in the nervous system, blood clotting and muscle contraction. Stored in bone they provide not only mechanical strength but also a reserve for periods of increased requirement (e.g., during egg laying) or periods of nutritional deficiency.

Calcium and phosphorus deficiencies can lead to abnormal skeletal development, or rickets in the growing chick, and osteoporosis in older birds. Although rickets is frequently associated with a deficiency of calcium, the condition is most likely to arise in situations of vitamin D deficiency (Wise, 1979). Osteoporosis results from calcium being removed from bone to meet other needs, and this causes porous and brittle bones (Long et al., 1984).

Newly hatched chicks need an immediate supply of dietary calcium for bone development. Since at this age chicks are osteoporotic, an absence of calcium or vitamin D makes this condition more pronounced.

The medullary cavity is the central area inside a bone where bone marrow is stored. Red bloods cells, white blood cells and fat calls are formed in the bone marrow and it has a vascular section which supplied the bone with nutrients and transports the cells around the body.

The first signs of a deficiency of calcium, phosphorus or vitamin D, or all of these, are:

•   Lameness
•   Stiff legs
•   Ruffled feathers
•   A reduction in growth
•   Leg bones appear rubbery
•   Joints become enlarged
•   A calcium deficient diet may cause paralysis followed by death

In growing pullets, a calcium deficiency can result in increased general activity and environmental pecking (Hughes and Wood-Gush, 1973). The pullet’s requirement for calcium is relatively low during the growing period, but the bird still needs properly balanced phosphorous and calcium in its diet. When laying starts the need is increased at least four times, largely for the production of eggshells (Jacob et al., 2003) as the egg shell is composed primarily of calcium carbonate. Thus an early sign of calcium deficiency in laying hens is the production of thin and soft-shelled eggs.

Calcium is stored in the medullary cavity of the bone capable of rapid calcium turnover (See diagram). Whereas caged hens may suffer calcium depletion and brittle bones, birds on the ground tend not to suffer as they recycle calcium and phosphorus through coprophagy (Jacob et al., 2003).

The nutritional role of phosphorus is closely related to that of calcium. The ratio of dietary calcium to phosphorus affects the absorption of both these elements. An excess of either can interfere this process and cause production losses.
Low dietary phosphorus during lay can lead to elevated incidence of cage layer fatigue, reduced bone ash, increased severity of osteoporosis, and diminished bone strength (Webster, 2004).

In addition to its function in bone, phosphorus also plays a key role in carbohydrate metabolism, fat metabolism, and the regulation of the acid-base balance of the body (Jacob et al., 2003).

Control and Prevention of Calcium and Phosphorus Deficiency

Encouraging birds to do more exercise as in free ranging systems will improve bone strength and minimize the risk of osteoporosis.

Generally, the calcium content of poultry feeds of plant origin is low. Prevention of deficiency requires the adequate dietary provision of calcium, but young birds should not be fed a high calcium layer diet as an excess of dietary calcium can tie up phosphorus making it unavailable, and may result in rickets. The balance between calcium and phosphorous is key. Excess calcium in the growing period can also result in kidney damage, visceral gout, calcium deposits in the ureter and mortality.
If all feed for the birds is bought in, the feed mill will balance calcium and phosphorous in the ration. Farmers who mill and mix their own feed should be particularly careful to avoid causing deficiencies. There is a difference in requirement for calcium between laying hens and broilers with laying hens having a higher need for calcium of around 4g per day – equivalent to the weight of an average eggshell. Soluble limestone grit or oyster shell grit may be used to provide a source of calcium for laying hens (Reid and Weber, 1976). Calcium may also be provided in the form of mixed grit. Mixed grit contains soluble grit composed of limestone, oyster shell and other mollusc shells, and insoluble grit in the form of granite and flint. Particle size affects calcium availability with larger particles being retained for longer in the upper digestive tract and calcium being released more slowly. Oyster shell for example provides a slow release of calcium. This may be important for the continuity of shell formation (Jacob et al., 2003).

Dolomitic limestone should not be fed to poultry as it contains at least 10% magnesium, and can interfere with calcium absorption creating a deficiency, as opposed to alleviating it.

Breeding may be an effective way of combating osteoporosis. Some genetic lines may be more prone to osteoporosis than others (Bell and Siller, 1962 cited by (Webster, 2004)). A study was conducted which looked at the genetic heritability of bone index and strength in five generations of while leg horn end-of-lay hens. Some bone strength traits were been shown to be moderately to strongly heritable (Bishop et al., 2000).

Phosphorus in plant material is only partly available to the chicken, and for periods of the bird’s development can become unavailable. For this reason, poultry feeds need supplementation with phosphorus (Hopkins et al., 1987). Microbial phytases can be used in reduced-P layer diets containing feeds with high levels of P bound up in the form of phytate e.g. rice bran (Tangendjaja et al., 2002).

An interaction between particle size and phosphorus concentration occurs when chicks are fed diets deficient in phosphorus. For example, whilst food efficiency increases with fine and pelleted corn diets, calcium and phytate phosphorus retention are greatest with coarse corn diets (Kilburn and Edwards, 2001).

Treating Calcium and Phosphorus Imbalances


Provided irreversible damage has not been done to bone structure, altering the calcium content of the diet should be effective. Expert nutritional advice should be sought regarding therapeutic inputs of calcium to deficient birds. Damaged bone structure may be improved by encouraging exercise, provided the diet has been improved.
A calcium boost using water-soluble sources can help get the diet back into balance. Providing ad lib oyster shell will then allow hens to take what they need for maintenance.

Source: FARM HEALTH ONLINE
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