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Department of pharmaceutics A.R College & G.H Patel Institute of Pharmacy 12/05/2010
List of contents
y Effect of physicochemical properties on parenteral absorption y Introduction
Polymer membrane permeation- controlled drug delivery Matrix diffusion-controlled drug delivery Microreservior partition-controlled drug delivery system Membrane matrix hybrid-type drug delivery system Osmotic pressure Vapor pressure Magnetically Hydration Hydrolysis
REFRENCES
Dissolution
Partitioning
Systematic circulation
Absorption
Drug solution in tissue fluid
Target tissue
Elimination
y Rate of dissolution of solid in formulation vehicle y Particle size and crystal habit y pH of the formulation y pKa of drug y Lipophillicity of the drug y Tissue fluid/vehicle partition coefficient y Solubility of drug at biological fluid at injection site y Presence of other ingredients in the formulation and their
continuous administration of crystalline hormone in the form of solid steroid pellet y But the release profile was not constant and can not be readily controlled in terms of precision of the release rate and duration of action y While it is possible to surgically implant and remove drugconcentrative devices or polymeric matrices, the requirement for such intervention could have a significant negative impact on the acceptability y Two approaches to this problem seem possible 1. Use of implanted electrically driven pumps 2. Use of erodible implants
controlled administration of drugs via implantation (1) Controlled drug delivery by diffusion process y Diffusion of the drug out of the device or solvent into the polymer ultimately contributes to the drug-release process y Release of the drug from the device is preprogrammed at a specific rate profile y This is accomplished by a system design which controls molecular diffusion of drug in or and/or across barrier medium surrounding the system y This systems can be further sub classified in to number of classes
(A)
1. Non porous membrane 2. Micro porous membrane 3. Semi permeable membrane y Here the drug formulation is totally or partially encapsulated within a drug reservoir compartment and the drug release surface is covered by a rate limiting polymeric membrane having a specific permeability for drug drug reservoir polymeric membrane Drug contained in a formulation
The dug reservoir can exist in to a solid , suspension or in a solution form and polymeric membrane fabricated in the form of non porous{homogenous or heterogeneous}, micro porous or semipermiable membrane. Encapsulation of drug formulation in to the reservoir compartment can be done by 1. Injection molding 2. Spray coating 3. microencapsulation Different shapes of the systems like sphere , cylinder or sheet can be fabricated An example of this type of implantable drug delivery system is A NORPLANT SUBDERMAL IMPLANT and OCUSERT SYSTEM
reservoir is prepared by homogenous dispersion of drug particles in a rate controlling polymer matrix fabricated from either a lipophillic or a hydrophilic polymer y The drug dispersion in a polymer matrix is done by 1. Blending finely divided drug particles with a liquid polymer or a viscous base followed by cross linking of the polymer chain 2. Mixing the drug with a polymer at an elevated temperature 3. Dissolving drug and polymer in a common solvent followe by solvent evaporation at elevated temperature or under vacuum y The resultant drug polymer dispersion is then molded or extruded to form a drug delivery devices of various shapes y Example is a nitro-dur TDDS
Gel layer
dispersion of aqueous suspension of a drug using a high energy dispersion technique in to a biocompatible polymer such as silicone elastomer to form a homogenous dispersion of many discrete , unreachable microscopic drug reservoir y Depending on the physicochemical properties of the drug and the desired rate of drug release , the device can be further coated with polymer to modify mechanism and rate of release y example is the transdermal nitro disc system
Polymer matrix
Microscopic Drug reservoir {liquid compartment}
Coating membrane
1. 2. 3. 4. 5.
Osmotic pressure activated Vapor pressure activated Magnetically activated Hydrolytic-activated Hydration activated
of the drug takes place due to osmotic pressure y Drug reservoir which can be either a solid or a suspension is contained in a semipermiable housing y The release is activated through a specially formed orifice and rate of release is modulated by controlling the osmotic gradient y Thus release rate is dependent on water permeability of membrane, solubility of osmogen, effective surface area of semipermiable housing as well as osmotic gradient y Representatative example of this type of implantable controlled release drug delivery system is alzet osmotic pump
contained in to an infusate chamber y By freely movable bellow the chamber is a pumping system physically separated from the vapors pressure chamber which contains vaporizable fluids such as a fluorocarbon y The fluorocarbon vaporizes at body temperature creating a vapor pressure that pushes bellow to move upward and forces the drug solution to get delivered
Coated polymer
A magnetic wave triggered mechanism is incorporated in to drug delivery device and drug can be triggered to be released at varying rate depending on the magnitude and duration of the electromagnetic energy applied
swelling process by tissue fluid at implantable site to activate drug release y In this system drug reservoir is dispersed in to swollable polymer matrix fabricated from hydrophilic polymer that become swollen upon hydration y Drug is released from microscopic water filled pore channels in to the polymer matrix and y Release rate of drug is controlled by swelling of the polymer matrix
Co(lactic-glycolic)polymer 2. Poly(orthoester) 3. Poly(anhydride) are used in fabrication of this type of implantable drug delivery system This system is made by dispersing loading dose of a drug with a biodegradable polymer , which is then molded in to pellet or a bead shaped implant Example is a LHRH{goserelin} releasing biodegradable sub dermal implant
1.
release of a drug is activated by some biochemical molecule in the body and its concentration at the implantable site via feedback mechanism
y And the rate of controlled release of drug is regulated
Hydrocortisone release
Erosion
Hydrocortisone
REFRENCES
1. NOVEL DRUG DELIVERY SYSTEM, Yie. W Chien, second edition, marcel dekker inc, page 381 2. DRUG DELIVERY SYSTEMS, Vasant V. Ranade Mannfred A. Hollinger Second Edition,