veterinary controlled dosage form

1. ROLE OF CONTROLLED
RELEASE IN VETERINARY
FORMULATION
PRSENENTED BY :
UNDE JAYESH SUNIL
M.S. (PHARM.) PHARMACEUTICS
GUIDED BY :
Dr. RAHUL SHUKLA
ASSISTANT PROFESSOR
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2.  HISTORY
 Veterinary controlled release drug delivery systems: Novel approaches
 OBJECTIVE : Veterinary Drug Delivery Systems
 The Major Challenges : Veterinary Pharmaceutical Company
 Factors Affecting Veterinary Drug Delivery
 Ruminal Drug Delivery Systems in Veterinary
 Ocular Drug Delivery System in Veterinary
 INTRAVAGINAL DRUG DELIVERY SYSTEMS
 INJECTABLE DRUG DELIVERY SYSTEMS
 MICROSPHERE
 ROLE OF FDA IN VETERNARINARY MEDICINE
 REFERENCES
CONTENTS
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3.  The word veterinary comes from the Latin word veterinae meaning "working animals".
 Veterinarian is a professional who practices veterinary medicine by treating diseases,
disorder, and injury in animal.
The Early Roots Of Veterinary Medicine
YEAR HISTORY
9,000 BC In the Middle East the Sheep herders used rudimentary
medical skills to treat their animals
between
4,000 – 3,000 BC
In Egypt medical treatment of animals became more
common, but was still largely undeveloped.
1,900 BC captured the first written accounts of veterinary medicine in
four sacred Hindu texts.
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4. 1762
• Claude Bourgelat established the first school of veterinary medicine in Lyon,
France.
1791
• Britain Society established London Veterinary College
1863
• In America the American Veterinary Medical Association came into being as a way
to promote the field of veterinary medicine.
Shalihotra , the first known veterinarian of the world, was an expert in horse
husbandry and medicine and composed a text Haya Ayurveda.
The Last Few Centuries Of Veterinary History
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5. Veterinary controlled release drug delivery systems: Novel
approaches
1.Geometrically Configured Diffusion Controlled System
 In such systems, it may be possible to produce a zero-order release profile by altering the
geometry of the device.
 Increase in surface area in order to offset the increase in diffusional distance the drug must
diffuse within the polymer matrix as drug release occurs.
 Drug release occurs by the mechanistic principles of a dispersed matrix system
Example- Paratect Flex Bolus
ethylene vinyl acetate
copolymer
1.which contains a
series of holes.
2.which pass completely
through the trilaminate
structure
drug release occurs
from both the
outermost edges
of the trilaminate
Used for the
prevention of
parasitic
gastroenteritis in
calves 5
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6. 2. Microchip Controlled Drug Delivery Systems
 The intelligent breeding device (IBD) is a single delivery system which is designed to deliver progesterone
continuously over a 10 day period.
 The rate, duration and timing of release of each of these drugs is controlled via a programmable
microchip.
 The IBD comprises an outer plastic sheath designed to protect the
electronic chip board which controls the rate and time of release of the
actives.
 The IBD was designed to administer progesterone, estradiol and
Prostaglandin at the required amounts, rates and times to precisely
Control the estrous cycle of cattle.
 The controlling chip, the plunger micropumps, the hormone reservoirs
and the batteries are arranged inside the container.
FIG: IBD 6
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7. 3. Osmotic push-melt system
 Veterinary drug delivery for delivery systems capable of delivering highly water insoluble compounds to
ruminants via the oral route.
 This need was met through the development of the 'Push-Melt' ruminal bolus.
 The product comprises a membrane cup that is extruded from cellulose acetate and various plasticizers
which is filled with an osmotic hydrogel tablet.
Mechanism of Operation
water enter into the pump
through a semipermeable
membrane
As the water enters the
osmotic layer, it compresses
the flexible reservoir
displacing the test solution
from the pump at a controlled,
predetermined rate.
Example
1.Rumistar® bolus for appetite and digestive stimulant.
2.IVOMEC® SR Bolus for delivery of ivermectin to cattle for control of
both endo- and ectoparasites’ FIG-Rumistar® bolus 7
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8. Hydrogels as polymers which have the ability to swell in water or in aqueous
solvents, and induce a liquid-gel transition.
Hydrogels results in the formation of a viscous gel which coats the surface of
the delivery system and acts as a barrier to drug release.
When this occurs, the drug is released at a slow rate, which is
theoretically controlled by its rate of diffusion through the gel barrier.
The release profile from such systems is dependent upon both the
surface area and the rate of advance of the boundary separating the
outer gelled portion from the anhydrated core.
Used for treatment degenerative diseases such as osteoarthritis and
intervertebral disc degeneration (IDD) have been the target of several
studies using these materials.
4. HYDROGEL
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9. Carrier Remarks Species
Methyl cellulose Well tolerated; blurring vision; newtonian
rheological behavior
R
Hydroxypropylmethyl cellulose Newtonian behavior at low concentrations but
pseudoplastic behavior at higher
concentrations.
R/H
Polyvinyl alcohol No blurring vision but discomfort at 42%;
good adhesive quality; excellent contact time;
very satisfactory wetting agent; newtonian
behavior
R/H
Carbopol No inflammation or discomfort; tolerable
blurred vision; pseudoplastic behavior
H
Pluronics Improved tolerance when mixed with isotonic
saline solution; pseudoplastic behavior
R
(H: human; R: rabbit.)
Table : Hydrogels for the treatment of keratoconjunctivitis sicca
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10. • To minimize animal handling in order to reduce the stress
to animals and farmer from repeated administration.
• To reduce the cost of treatment in terms of money .
• To reduce time spent by the end user on drug
administration.
• To treat the range of animals that could benefit from
receiving the medication.
OBJECTIVE : Veterinary Drug Delivery Systems
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11. The Major Challenges : Veterinary Pharmaceutical Company
1. Biopharmaceutical aspects relating to the specific route of delivery.
2. complexity of the environment related to dosage form .
3. Variations between and within animals.
4. Smaller overall commercial market.
5. Smaller profit margin.
6. Less research dollars with which to develop products.
7. Selection of excipients and polymers (must be cheap).
8. Manufacturing methods (must be efficient and cost effective).
9. Need a heavy responsible marketing team.
10. Development costs for drug approval.
11. Manufacturing and production process. 11
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12.  The diversity of species and breeds:
• Affecting the design and performance of veterinary dosage forms
• Species differences in metabolism can affect elimination of drug as well as large differences in the
half-life drugs
Table: Half-life of drugs measured in cattle, horses, dogs, cats and human
DRUG Ruminant
(hrs)
Horse
(hrs)
Dog
(hrs)
Cat
(hrs)
Human
(hrs)
Pentobarbital 0.8 1.5 4.5 4.9 22.3
Amphetamine 0.6 1.4 4.5 6.5 10-15
Salicylate 0.8 1 8.6 35 4-8
Sulfadimethoxine 9 11.3 13.2 10.2 40
Factors Affecting Veterinary Drug Delivery
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13.  Differences in animal weight
• Differences in animal weight that occur both among and within species present another
veterinary product development challenge.
• The variation in body weight can cause under-dosing or over-dosing can be a problem in
terms of efficacy and safety for potent drugs
TABLE : Comparison of the body weight ranges for various species
Species Weight range (kg)
Cat 1–4
Dog 3–43
Horse 408–433
Cattle (beef) 266–641
Dairy cow 600–700
Sheep 54–66
Total dose
can range
over 12-fold
within dog
breeds
Total dose can
range over
700-fold
between small
and large
animals
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14.  Free choice acceptance
 Approach for developing a palatable oral dosage form is to add a yeast-based or a meat-based flavor to the tablet
blend.
 If there is an odour issue need to consider other approaches for odor masking.
Free choice acceptance rates in dogs (%)
Plain tablet (no flavour) Flavoured tablet
Bland drug 60 100
Bitter drug 40 90–100
Odorous drug 20 55
Table : Free choice acceptance in dogs for a bland drug, a bitter drug and an odorous drug
COMTIBILIT
Y OF API
AND
FLAVOUR
GLOBALLY
ACCEPTABL
E
REGULATO
Y
APPROVAL
ACCEPTABL
E BY DOGS
AND CATS
STABILITY
OF
FLAVORS
CHARATARI
Z--ATION
OF
FLAVOUR
POINTS TO BE
CONSIDER AT
THE TIME OF
PALATABLE
ORAL PRODUCT
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15. Ruminant vs Non Ruminant
Ruminant
 Four compartments stomach
 Prominent microbial digestion
 Longer time to digest plant material
 Maximum digestion and absorption takes
place in rumen
 Has alkaline saliva
 Undergo regurgitation
 Single compartment stomach
 Enzymatic digestion
 Competitively less time to digest
 Maximum digestion and absorption takes
place in intestine
 Has neutral saliva
 Do not undergo regurgitation
Rumen
Reticulum
Omasum
Abomasum
Stomach
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16. Ruminal Drug Delivery Systems
Ruminal drug delivery systems provide for the long-term exposure to the bioactive material from a single
handling of the animal for administration.
Mechanism of Ruminal drug delivery systems
1. Density
A)High-density objects will remain in the reticulum for extended periods.
B)The minimum density of an object needed to avoid regurgitation
varies with animal between 2.25 and 3.5 g/cm³
C)While penned animals like dogs capable of retaining objects with a
density as low as 1.8 g/cm³
2. Variable geometry
 This is normally accomplished using a design that leads to a significant
expansion of at least one dimension of the device following its introduction
into the reticulo-rumen cavity.
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17.  Introduced the approach of incorporating polymeric 'wings' that are
constrained by a water soluble tape or adhesive during administration.
 Upon passage into the rumen, the tape or adhesive dissolves and the
wings expand thereby preventing regurgitation.
Trade name Material used Duration of the
release
DRUG
Paratec Flex® Ethylene– vinyl
acetate
90 days Morantel tartrate
Chronomintic® Ethylene– vinyl
acetate + Iron
powder
90 days Levamisole
hydrochloride
Ruminsert Bolus® cellulose acetate+
Metal
135 days Ivermectin
TABLE : Marketed ruminal dosage forms intended for administration via the oral
route in cattle
folded wings
Polymer
expanded wings
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18. Ocular Drug Delivery System in Veterinary
 Ocular drug delivery to develop delivery systems which prolong the time the drug is in contact with
ocular tissue.
 The drug may bind to proteins in the aqueous humor which can have a positive effect when it becomes
a depot-type drug delivery complex.
1.Hydrogels
 It increase in ocular residence time as a result of a reduction in drainage rate through
enhanced viscosity and mucoadhesive properties.
 Hydrogels like Methyl cellulose, Hydroxypropyl cellulose , Polyvinyl alcohol, Gelrite ,
Carbopol , Sodium hyaluronate etc.
2.Insert
 These are solid devices delivering drugs to the anterior segment of the eye that are denoted
by the general name insert.
 These inserts are placed in the lower fornix and, less frequently, in the upper fornix, or on the
cornea.
 Inserts can be classified according to their solubility behavior as soluble, insoluble or
bioerodible inserts.
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19. INTRAVAGINAL DRUG DELIVERY SYSTEMS
 Intravaginal Drug Delivery System have been developed for intravaginal administration to livestock
with the aim of controlling the estrous cycle.
 Specifically, these compounds include hormone like progesterone, methyl acetoxy progesterone,
fluorogestone acetate and estradiol benzoate.
 Commercially available intravaginal veterinary drug delivery systems is PRID, CIDR-G, CIDR-S and
CIDR-B.
 Progesterone containing intravaginal drug delivery system
(PRID- Progesterone Releasing Intravaginal Device)
1) They aimed at releasing sufficient quantities of progesterone
continuously to control the estrous cycle of cattle.
2) PRID device induce a mucopurulent discharge during insertion.
3) PRID are manufactured from silicone.
4) After insertion, either the entire device expands outwards. FIG – PRID
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20. 1) CIDRs (Controlled Internal Drug Release) are an intravaginal progesterone insert used in the beef cattle,
dairy cattle, goat and sheep.
2) The progesterone is released at a controlled rate into the bloodstream after insertion.
3) The CIDR is designed as a T shaped nylon spine molded with a silicone rubber skin, which contains
progesterone.
4) The wings of the CIDR insert have the ability to be folded together in order to insert intravaginally.
 CIDRs (Controlled Internal Drug Release)
CIDR-B
USED IN CATTLE ,HORSE,
BUFFALO
CIDR-G
• USED IN SHEEP AND
GOAT
CIDR-S
• USED IN PIGS AND
GOAT 20
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21. INJECTABLE SYSTEMS
Prepare a
solution of drug
that was close to
saturation.
So that upon injection
the drug was slowly
deposit at a fine
precipitation.
Creating a drug
suspension
depot at
injection site.
The resulting
formulation
succeeded providing
release of drug over
2-3 days.
THEORY
EXAMPLE
Ivermectin has been formulated
into propylene glycol and glycerol
Formal and administered
subcutaneously to cattle
and pigs.
The half-life of the drug, combined
with its formulation into a nonaqueous
vehicle which allows for the creation of
a depot at the site of injection
prolongs the
action of the
for over a
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22. 1) They are monolithic systems consisting of a polymeric matrix in which the drug
substance is either dispersed or dissolved, depending on its solubility.
2) Microspheres consist of a multiplicity of small spherical particles each 1-200 μm
in diameter .
3) Copolymers of the poly-lactide-co-glycolide (PLG) and polyglycolide esters,
as well as poly (e-caprolactone) and their copolymers have been used to produce
small biodegradable microspheres.
4) PLG microspheres have been administered in a variety of ways like Parenteral,
oral and intranasal routes.
PLG microspheres have great potential for wide use
1) Bovine parainfluenza 3 vims (PI3) has been encapsulated in PLG microspheres
and administered as a subcutaneous (SC) injectable vaccine for cattle.
2) Several microsphere products have been emerging for the delivery of
antibiotics into the synovial fluid of equine joints and steroids to control oestrus
and ovulation in female horse.
MICROSPHERE
Bovine parainfluenza
3 vims (PI3)
Antibiotics 22
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23. The Food and Drug Administration (FDA) added a Veterinary Medical
Branch in 1965 to oversee veterinary pharmaceuticals.
It later became the Center for Veterinary Medicine (CVM).
The work of the CVM is still essential in that it oversees regulations
relating to food, medicine, and other products for animals.
ROLE OF FDA IN VETERNARINARY MEDICINE
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24. References
 Vandamme TF, Ellis KJ. Issues and challenges in developing ruminal drug delivery systems. Adv Drug
Delivery Rev. 2004;56(10):1415–36.
 Ahmed I, Kasraian K. Pharmaceutical challenges in veterinary product development. Adv Drug
Delivery Rev. 2002;54(6):871–82.
 Cardinal JR, Witchey-Lakshmanan LC. Drug delivery in veterinary medicine. Treatise Control Drug
Deliv Fundam. 2017;28:465–89.
 Rathbone MJ, Macmillan KL, Bunt CR, Burggraaf S. Conceptual and commercially available
intravaginal veterinary drug delivery systems. Adv Drug Deliv Rev. 1997;28(3):363–92.
 Rathbone MJ. The pharmaceutical scientists’ role in animal production: An historical and future look
at the evolving area of controlled drug delivery in animal production. Proc New Zeal Soc Anim Prod
[Internet]. 2000.
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25. THANK YOU
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