VETRNARY DOSAGES FORMS

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What's mean by veterinary dosage forms ?

• The medication used for treatment , diagnosis purpose or curing the diseases in animals are known as veterinary dosage forms.

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For your knowledge • Animals are not like humans• Animals having different species

as below….o HerbivorousEg. Horse, sheep, goatso OmnivorousEg. Pigo CarnivorousEg. Dogs, cat

BETWEEN-SPECIES DIFFRENCES

A. Comparative physiology of digestive systems.

B. Skin typeC. RespirationD. Behavior

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Comparative physiology of digestive systems.

• Every species having differences bet there digestive systems

• Eg. Pigs, Dog, Cats having intestinal PH 5.3 Horse having intestinal PH 7

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Skin type• The drug formulation for topical use between

species difference might be expected because of nature of skin.

• Eg. cows, Dog, Cats not having ability to sweat

profusely Pigs have extensive layer of keratin

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Respiration

• Important for successful inhalation therapy• The absorption of drug by respiration depends

upon the drug, particle size, inspiration volume and rate

• Eg.Respiration rates of birds varies form 46 to 380 respiration/minHorse:- 12/mincow :- 30/min

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Behavior• Water loving breeds shows problems.• Cat are constant groomers, any drug

substance applied topically likely to be injected.

Even disinfectant and other chemicals causes toxicity

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Physiological consideration

1.Drug sensitivity2.Age3.Sex4.Pregnancy5.Disease states

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Drug sensitivity

• Variation in the drug sensitivity due to species difference

• Eg. Dioxithion is highly sensitive in bull than

other

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Age

• New born animals susceptible to toxic effect by many depressant & stimulant of CNS

• New born having deficiency in drug elimination

• New born having more water content as compare to mature animal uit affect the drug distribution

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Sex

• Drug metabolism varies by sex as male or female

• Eg. male rats having the high rate of

metabolism as compare to female rats

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Pregnancy

• Pregnancy causes dehydration • It affect the distribution of the drug

• Due to this factors drug formulation for animal in pregnancy state taken in consideration

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Disease states

• Distribution of drug affected by disease state like renal failure, heart failure, dehydration..

• This is the physiological condition taken in

consideration

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ReasonAnimal health past few years become more essential

for the following reasons1. According to Animal Health Institute, domestic

sales survey 4.32 billion dollars priced. 2. Zoonosis – the diseases of animals may

secondarily transferred to humans.In 1960 and 1970 two pharmacy colleges offered the

courses in agricultural pharmacy and veterinary therapeutics

University of Iowa college of pharmacySouth Dakota university

Some pharmacological agents that are used exclusively in animals

• 1) Xylazine: sedative, analgesic • 2) Detomidine: preanasthetic medication • 3) Acepromazine: preanasthetic medication • 4) Flunixin: anti-inflammatory • 5) Azeperone: preanasthetic medication

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• Some of the drugs can not be used in animals, those are

• chloramphenicol, • diethylstilbestrol and • vancomycin.

CLASSIFICATION OF VETERINARY DELIVERY DEVICES

• Because of the variety of dosage forms in veterinary medicine and the diversity of animal and bird species treated, drug or dosage delivery sometimes requires the development of specific devices to ensure fast, safe, effective and low cost efficient treatment.

i. Oral devicesii. Topical devicesiii. Parental devicesiv. Nasal devices

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1. Oral devices a. Balling guns b. Esophageal delivery devices c. Drench syringes d. Liquid drench guns e. Powder drench guns f. Paste Dispensers g. Water medication metering devices h. Rumen lodging devices i. Hollow bits j. Non pyloric passage devices k. Miscellaneous oral dose dispensers l. Buyoant devices m. Prolonged release devices 19

2. Topical devices a. Pour on, spot on application b. Dust bags c. Spray race and dip d. Teat dip e. Aerosol Dispensers f. Flea and tick collars g. Percutaneous devices

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3. Parenteral devices

• Single dose syringe Syringes are used to express the hydrated OTC Free

Injection Formula through the back of the Valve and into the palm.

Fig. 16: single dose syringe 21

• Automatic syringes The vial holder model of this

automatic syringe is often used for vaccination or injection of swine.

Fig. 17: Automatic syringe • Multi compartment syringes

Multi-compartment syringe for storing two or more substances in separate compartments.

Fig. 18: Multi compartment syringe 22

• Pole mounted syringe : Used for remote administration of medicaments. Long needles are used which are secured on housing that supports the needle to prevent its breakage.

• Mastitis syringes : Drug formulation can be delivered to the site of infection in a cow with mastitis. Needles can be inserted directly into the mammary gland through the teat canal.

• Jet injectors : Dose of liquid medicaments is expelled under extremely high pressure against epidermis of the animals. Used to vaccinate a large number of animals and birds.

• Projectile delivery system : Used to deliver drug parenterally from a distance.

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4.Implanting devices

Three types of Implanting devices are used in veterinary practices:

• Pellet Implanting devices • Ball Implanting devices• Molten Implanting devices

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• Implants: These are generally smaller and are designed to implant beneath the surface of the skin subcutaneously or intramuscularly.

Fig. 18: Implants

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Intrauterine drug dispenser

Used for local and systemic effect in animal for local effect prostaglandins, anti fertility agents, oxytocic agents are used. Drugs with short biological half life can be used.

Vaginal drug dispenser Used for synchronization of estrus. Synchronization will increase productivity. E.g. flurogestone acetate, medroxy progesterone acetate as sponge. Miscellaneous syringes It includes: Gas powdered hypodermic syringe Motor actuated syringe Flexible needle syringe

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5.Nasal devices

Used for delivery of vaccines as solutions or powders. It includes:

• i. Automatic single or multiple dose syringe • ii. Single dose dropper vial • iii. Spray dispensers • iv. Powder mist dispensers

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Rational Dosage Forms

• Form economical view point the best way to administered drug would be in natural solids or liquid forms

• Why medication are dispensed in a form other to an their natural states. Some drug required protection form atmospheric oxygen & moisture

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Formulation of drug dosages forms for animals

• Solid • Liquid oral • Parenteral • Pastes • Pellets and • Implants

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Solid Dosage forms• There are many similarities and differences in

the anatomy and physiology of mammals, birds and humans

Tablets and boluses: • These are less popular for animals because of their

administration may be time consuming, hazardous, uncertain in tablet swallowing, and they may spit out or dropped from the mouth.

• This can be overcome by use of acceptable odors, flavors, sweeteners.

• Tablet advantages over other dosage forms low manufacturing cost, stability, palatability problems, uniform dosage and convenience in packaging

Solid Dosage Forms

Odour Flavour Sweetner

By using this improve acceptance of tablet By chewing animals crushed the tablets

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Flavors that animals prefer include

• Dog prefers Beef, Chicken, Peanut Butter, Liver, Raspberry, Strawberry.

• Cat prefers Tuna, Chicken, Beef, Cheese, Peanut Butter, Liver, Butterscotch.

• Bird prefers Grape, Orange, Tutti-Frutti.• Horse prefers Apple, Creamy Caramel,

Molasses, Licorice, Cherry.

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Solid Dosage Forms Dosing based on weight Eg. cow required high dose so we can’t

prescribe 15 gm of drug for each 150 lb of body weight. Thus 600 lb cow would required 60 gm drug. So this is complicated

To Overcome this problems : capsule shaped or cylindrical shaped tablet commonly called BOLUS

The instrument used to hold and drop it in to animal mouth is balling guns

It’s difficult to give horse but useful in cow

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• Drugs are given on the basis of weight or body surface area

• The labeling of solid dosage forms, must be stated in mg or g per kg of body weight

• A special tablet BOLUSE is commonly used to provide the large doses, it can range from 3 to 16 gm in weight

• Boluses are capsule shaped or cylindrical • Boluses are administered by an apparatus called balling

gun, consisting of a barrel with a plunger that can hold one or more boluses

• The tube inserted in to the animal mouth over the base of tongue and such animal swallows the plunger is depressed.

• The bolus is expelled in to the gullet of animal, after it swallowed by reflex

• Bolus formulation poses challenges because of the high to excipients ratio• Less room left for diluents, binders and other additives• Cattle or sheep, possible to utilize the concept of long acting boluses, which

stays in GIT more than 12 hrs.• The density is the critical factor to maintain the retention

Feed additivesFeed additive premix (type A) are formulated to contain bulk drug and excipient

in a form that may ready combine with an animal feed The feed route is using for mainly prophylactic purpose and growth promotion of

animal . The most of the premixes contains grain carrierRice hullsCorn germ mealCorn mealCorn gluten

In which active drug is lightly bound or absorbed on the surface, the carrier functions by absorbing the small particles of drug on the surface, The carrier usually be two thirds or more in concentration .

• An oil may be added to bind the drug and the carrier

• To prevent caking , an anti caking agent such as silicon dioxide or magnesium aluminium silicate can be incorporated

• factor considered in formulation 1. Drug concentration 2. Moisture content of drug and carrier3. Electrostatic charges4. pH 5. Flow of powders

Drinking water medications

• The medications formulated as1. Dry powders for reconstitution 2. Concentrated solutions

Unhealthy animals allow to drink water continuously.

Water as medium for drug solubility and quick absorption.

Concentration of drug in water to be half only, this problem may overcome by its limited solubility.

The powder medication is dissolved at the time of administration in to water to make a stock solution

• In addition, the dry powders are usually formulated with sugar as lactose or dextrose.

• The use of these may cause a build-up of bacteria and fungi in water lines

• The drug stability in water must be stated in label

Oral Liquid Dosage Form

• Solution and Suspension• Mostly used as aqueous solution• If drug substance is not soluble in water the

o Co-solvanto Surfactanto Solubilisero Complexing agent– Or vegetable oil are used

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Suspension• Useful for drug which having lack of solubility

• By add suspending agent suspension was prepared

• Mostly preffered to aqueous suspension

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Parenteral Dosage Form

Parenteral dosage forms Aqueous, organic and oily solutions Emulsions Suspensions

It prepared same as human

Indeed many products of human given animal without any modification

It must be Sterile Free form pyrogen

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Paste

It’s more convenient to pets like cats, dogs

It’s injected in the mouth due to paste its not come out easily and absorb in mouth

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Oral pastes and gelsSemi fluid masses can be administered from a flexible

tube, syringe or using deviceAdvantage of these are cannot be expelled out animal

mouth.Medication may be readily and easily with a paste. A proper consistency to adheres to the tongue or buccal

cavity.Characteristics of pastes1. when placed in palm and hand is inverted it should

remain without falling2. When ejected fro applicator, should break cleanly3. No paste should continue to ooze from applicator4. Free from air bubbles

• Three types of vehicles used in formulation of paste and gels are

1. Aqueous bases2. Oil or oleaginous bases3. Organic solventsAqueous base is the least expensive vehicle and

poses no toxicityGlycerin, glycols, natural or synthetic gums,

polymers used to increase the viscosity, cohesiveness and plasticity

To overcome the separation of water gel, can use absorbing materials like MCC, kaolin, colloidal silicone dioxide, starch

Oleaginous bases consists of vegetable oil with aluminum monostearate, colloidal silica, and xanthan gum

Glycerin , propylene glycol and poly ethylene glycol thicked with carboxy vinyl polymers provide organic bases

Pallet & Pallet implantsFor long acting hormone therapySolution is clean & flow readilyThis implant inside the body of animalPellets implants The subcutaneous implantation of a tablet or

pellet will provide a long acting hormone therapy. Pellets implanted on the dorsal surface of a cow’s ear are used for controlling estrous, improving growth and enhancing feed efficiency. Pellet implants of diethylstilbesterol were used in caponising poultry. 47

Mastitis Products

Mastitis has been define as inflammation of mammary gland due to infection by bacterial or mycotic pathogens

When it occurs in sheep, cow, it greatest economical because it reduces the milk production

It overcome by systematic administration of an antibiotic by topical or therapautic treatment

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Drenches and tubing products• Horses are administered certain medications by running

lubricated tube up through the nostrils and down in to stomach

• A funnel attached to the tube is held above the horses head and liquid medication is poured down the tube. Known as tubing

• Normal dose by this method is 10 OZ • Wetting agents are used to increase the flow rate.• Thicking and suspending agents are contraindicated to

resist the flow • The administration of drug to animals by pouring a

liquid medication down an animal throat is called “drenching”

Topical dosage formsFour types of topical dosage forms are

1. Pour on /spot on applications2. Dust bags3. Dips4. Flea and tick collars

Pour on/spot on applicationsThese are the liquid products effect systemic activity after being poured on to

animal backline or applied as one spot concentrate on the animal back Spot on s mainly used for grubs and lice Eg: levimisole , broad spectrum anti helminthic activity These formulation contains organiophosphorus insecticides or antihelminthic

dissolved in organic solvents as DMSO or aromatic hydrocarbonsThe advantages of these formulations are 1. Elimination of risk of trauma and damage at injection site2. No special skills are required for application 3. Sterile preparations are not necessary 4. Troublesome animals are dosed easily 5. Speed of treatment is quick

Dust bags • Cattle are treated with insecticide powders through use of a

device called a dust bag.• Dosing accomplished by animals brushing against the bag

as they walk beside or under it • This bag has an inner porous storage bag containing the

insecticide dust formulation • Forced –use bags are hung in door ways or tree or poleDIPS• For control of ectoparasites in economic animals, dipping is

an extensively used method• A dip formulation containing the drug is diluted in a large

dipping bath through which the animal is driven • This bath must be long, wide, and deep enough to cause

immersion of the animal • It must be non toxic to the animal but toxic to ectoparasites

Flea and tick collars • This dosage form is most familiar companion animals like dogs and

cats • There are two types of flea and tick collars

– Vaporous – Powder producing collars

• Both containing the insecticide and a plasticized solid thermoplastic resin

• Vaporous collar contains relatively high vapor pressure liquid pesticide mixed throughout the collar

• The pesticide is slowly released and fills the atmosphere adjacent to the animal , that kills the pest but innocuous to the animal

• The powder producing collar contain a solid solution of the drug in the resin

• Shortly after the collar is processed the particles migrate from within the body of resin and form a coating of particles known as bloom

Ticks and fleas migrate through the neck area of the animal as they contact the active pesticide is released and kills the pest

Miscellaneous dosage formsPharmacists are responsible to compounding of ear

preparations for pets that are not commercially available

Nebuliozers and aerosols are starting to be used in small animals

Percutaneous patches are used in small animalsEg; fentanyl

Over the counter drugs• Some OTC drugs used in small animals but in others

should not be used, Due to the differences in absorption , receptor types, metabolism and other in digestive system and dosage than in human

• Anti inflammatories are used cautiously in dogs and cats – Eg; aspirin

• Acetaminophen and ibuprofen are two OTC drugs highly toxic to small animals, cause blood dyscrasias

• Anti histamines are widely used in small animals to control allergies reactions– Eg: diphenhydramine

• Anti diarrheal are used in dogs.• Creams and lotions may be used in animals , although

they can be licked off.

Containers

Mostly used plastics .

Having following problemso Are less impervious to passage of oxygen than

glasso Can not be sterilize by heato Deformed by some product

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Labeling of veterinary drugs:1.Name and address of veterinarian2.Active ingredients3.Date dispensed and expire date 4.Directions for use5.Cautionary statements6.Name and address of pharmacy / pharmacist

dispensing the medication

Evaluation

1) Products – All tests of a dosage form up to In vitro evaluation including chemical assays and microbial assays .

2) Target Animal Tolerance Studies 1. General tolerance 2. Local tolerance ● Tolerance testing of Injectables ● Tolerance testing of products intended for Dermal Applications ● Tolerance testing of products intended for Oral administration

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Physical evaluation Tablets

1. Disintegration time2. Weight variation3. Hardness and friability4. Compaction5. Particle size and crystal structure6. Flowability of granules.7. Moisture content

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1. Colour2. Odour3. Taste

Physical evaluation of Oral Liquids1. Clarity of solution2. PH3. Viscosity4. Solution time

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Physical evaluation Suspensions and Emulsions1. PH2. Viscosity3. Re-dispersion4. Flocculation5. Settling/Creaming

Physical evaluation of Pastes• pH.• Viscosity.• Particle size Distribution.• Texture.

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Physical evaluation of Gels• pH.• Viscosity.• Clarity.• Texture.• Swelling.

Physical evaluation of Parenterals

• Clarity.• pH.• Tonicity.• Syringeability.Other Tests• Sterility.• Microbial Assay.• Pyrogen testing

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Physical evaluation of Pellets

• Locomotion.• Signs of pain.• infection, migration, or rejection

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Physical evaluation of Implants

• Angle of repose, hausner’s ratio, • Compressibility index, • Bulk density, true density and Granule density, • Flow rate, • Carr’s Index. • In-vitro Dissolution studies

Controlling Authorities of Veterinary Products

• Animal Welfare and Animal Husbandry Department, undertaking of the Government of India.

• Animal Health Institute (AHI). • US FDA ( Food & Drug Administration ). • Animal Drugs Availability Act 1996. • Animal Medicinal Drugs Clarification Act 1968

(AMDOCA)

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What drugs can be legally marketed?

• FDA approved products – NADA-new animal drug application (pioneer) – ANADA-abbreviated NADA (generic) – CNADA-conditionally approved NADA – Indexed minor species products

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VETERINARY DRUG APPROVAL PROCEDURE• Like all human drugs, a new animal drug has to

be approved by FDA before it is sold and marketed to the public.

• And like the human drug approval process, the new animal drug approval process is complicated.

• Before a new animal drug may receive FDA approval, the drug sponsor must demonstrate that the new animal drug product is safe and effective when used as directed on the label.

• Drug sponsors submit to FDA a New Animal Drug Application (NADA) along with supporting data, including all unexpected side effects (adverse effects) associated with the drug product’s use. 65

• The drug sponsor must show that it can manufacture the drug product so that the product’s composition is consistent from batch to batch, that the product’s active ingredients come from reliable sources, and that it follows good manufacturing practices while making the product.

• If the drug product is to be used in a food-producing animal, residues in food products (such as meat and milk) from that animal must be shown to be safe for human consumption.

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U.S. REGULATORY REQUIREMENTS FOR ANIMAL DRUGS

• The center for veterinary medicine of the Food and drug administration has the responsibility for review and approval of animal drugs

• The mechanism for review and approval of animal drugs is through the submission of Form 356( NADA) new animal drug application

• Animal feeds containing drugs must also be approved by submission of Form FD 1900, animal feed application

Before approval of new animal drug application , the Center For Veterinary Medicine (CVM) may require a manufacturing facilities visit called a preapproval inspection.

The GMP regulations are used as a guide for this audit by inspectors from the compliance division of FDA.

The requirements for laboratory data, manufacturing equipment are same for drugs used in humans or animals

Stepwise Regulatory Requirements For Approval Of Animal Drugs.

1. Pre-INAD (Investigational New Animal Drug) Meetings.

• Prior to opening an Investigational New Animal Drug (INAD) file

• Pre-INAD meetings for innovative products • – Inform CVM about the product • – Learn about the approval process • Pilot studies in laboratory research animals (non-client

owned animals) – Must comply with 21 CFR (Code of Federal Regulation)

511.1(a) 69

2. INAD (Investigational New Animal Drug)

• Open the INAD – Provide as much product information to CVM

as possible • Product characterization – Can submit when you open the INAD • Request a meeting to discuss product

characterization and development plan

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• Pilot studies in client owned animals – Must comply with 21 CFR 511.1(b) – INAD exemption allows shipment of

investigational drug in interstate commerce • Sponsor responsibilities under the INAD – Labeling, data collection, records, drug

accountability, animal disposition, investigator qualifications

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INAD (Investigational New Animal Drug)

3. Pre-submission Conference

• After sufficient product characterization

• Work together to determine the types of studies that will be used to support safety, effectiveness, and manufacturing

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4. Protocols

• May be submitted to CVM for review • Safety, effectiveness, manufacturing • CVM concurrence means we fundamentally

agree with the study design

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Major Technical Sections

• Safety – Target animal, special studies • Effectiveness – Substantial evidence, field

study, conditions of use • Manufacturing – Identity, strength, quality,

purity • Human Food Safety • Environmental

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Minor Technical Sections

• Labeling • All Other Information• FOI (Freedom of Information)

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Administrative NADA

• Administrative New Animal Drug Application (NADA)

• Administrative application submitted after all technical sections are completed

• Completion of Administrative NADA = FDA approved product

• Non-administrative NADA

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