Polymer membrane permeation cdds

1. “POLYMER MEMBRANE PERMEATION CONTROLLED DRUG DELIVERY SYSTEM ” Presentation ON

2. Sustained release, sustained action, controlled release, extended action, timed release dosage forms are the terms used to identify drug delivery systems that are designed to achieve a prolonged therapeutic effect by continuously releasing medication over an extended period of time after the administration of single dose. The term “Controlled release” has become associated with those systems from which therapeutic agents may be automatically delivered at predefined rates over a long period of time. But, there are some confusion in terminology between “Controlled release” & “Sustained release” INTRODUCTION

3. Sustained Release : The term sustained release has been constantly used to describe a pharmaceutical dosage form formulated to retard the release of a therapeutic agent such that its appearance in the systemic circulation is delayed &/or prolonged & its plasma profile is sustained in duration. Controlled Release : This term on the other hand, has a meaning that goes beyond the scope of sustained drug action. It also implies a predictability & reproducibility in the drug release kinetics, which means that the release of drug ingredient from a controlled delivery system proceeds at a rate profile that is not only predictable kinetically, but also reproducible from one unit to another.

4. An ideal controlled drug delivery system is the one which delivers the drug at a predetermined rate, locally or systematically for a specified period of time.

5. Biopharmaceutic Characteristics of the Drug Molecular weight, Aqueous solubility, Partition coefficient, Drug Pka and Ionization, Route of administration, Drug stability etc Pharmacokinetic Characteristics of the Drug Absorption rate, Elimination Half-Life, Rate of metabolism etc. Pharmacodynamic Characteristics of the Drug Therapeutic Range, Therapeutic index, Plasma concentration response relatioship Design of Controlled Drug Delivery

6. These are some of the first materials selected for delivery systems bases on their intended non-biological physical properties: Polyurethanes for elasticity Polysiloxanes for insulating ability Polymethyl methacrylate for physical strength and transparency Polyvinyl alcohol for hydrophilicity and swelling Polyvinyl pyrrolidone for suspension capabilities Polymers for Controlled Release

7. These polymers became usable in controlled delivery due to their inert physical characteristics and being free of leachable impurities Poly 2-hydroxy ethyl methacrylate Poly N-vinyl pyrrolidone Polyvinyl alcohol Polyacrylic acid Polyethylene glycol Polymethacrylic acid Current Polymers used in Controlled Drug Delivery

8. Number of approaches have been developed to achieve controlled administration of drugs via implantation (1) Controlled drug delivery by diffusion process Diffusion of the drug out of the device or solvent into the polymer ultimately contributes to the drug-release process Release of the drug from the device is preprogrammed at a specific rate profile This is accomplished by a system design which controls molecular diffusion of drug in or and/or across barrier medium surrounding the system This systems can be further sub classified in to number of classes

9. Based on their technical sophistication : Rate preprogrammed drug delivery system Activation-modulated drug delivery system Feedback-regulated drug delivery system Site targeting drug delivery system CLASSIFICATION

10. In this group , the release of drug molecule from the system has been preprogrammed at specific rate profile. They can be classified as Polymer membrane permeation-controlled drug delivery system Polymer matrix diffusion-controlled drug delivery system Micro- reservior partition-controlled drug delivery system Rate Preprogrammed Drug Delivery System

11. In this type, drug is totally or partially encapsulated within drug reservoir. Its drug release surface is covered by a rate-controlling polymeric membrane having a specific permeability . Drug reservoir may exist in solid, suspension or solution form Polymer Membrane Permeation-Controlled Drug Delivery System drug reservoir Polymeric membrane Drug contained in a formulation

12. Polymer membrane permeation- controlled drug delivery using Non porous membrane Micro porous membrane Semi permeable membrane

13. 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 semi-permeable membrane. Encapsulation of drug formulation in to the reservoir compartment can be done by: Injection molding Spray coating 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 Systems. Polymer Membrane Permeation-Controlled Drug Delivery System

14. Fig: Diagrammatic representation of membrane permeation controlled system in which drug reservoir is stacked between the layers of drug impermeable plastic laminate and rate controlling membrane and below which the adhesive layers faces the skin surface.

15. Release of drug molecules is controlled by : Partition coefficient of the drug molecule. Diffusivity of the drug molecule. The thickness of the rate controlling membrane .

16. The rate of drug release is defined by , Q = K m/r K a/m D d D m x C R t K m/r D m h d + K a/m D d h m Where, K m/r & K a/m = partition coefficient of the drug molecule from reservoir to rate controlling membrane & from membrane to aq. Layer respectively. D d & D m = diffusion coefficient of rate controlling membrane & aqueous diffusion layer respectively. hm & hd = thickness of rate controlling membrane & aqueous diffusion layer respectively. C R – drug conc. In reservoir compartment .

17. Ocusert system In this device, the solid drug reservoir, which is a thin disc of pilocarpine alginate, is sandwiched between two transparent sheets of microporous membrane fabricated from ethyvinly acetate copolymer . It is designed permit the tear fluid to penetrate the microporous membranes, to dissolve and to carry out pilocarpine at a constant rate of 20 to 40 mcg/hr for weekly management of glaucoma.

18. Norplant is implanted under the skin in the upper arm of a woman, by creating a small incision. inserting the capsules in a fanlike shape. Insertion of Norplant usually takes 15 minutes the contraceptive works within 24 hours and lasts up to five years.

19. The drug reservoir is a suspension of progesterone & barium sulphate in silicone medical fluid & is encapsulated in the vertical limb of a T-shaped device walled by a non-porous membrane of ethylene-vinyl acetate co-polymer . It is designed to deliver natural progesterone continuously in uterine cavity at a daily dosage rate of at least 65 μ g/day to achieve contraception for 1 year. Ex. Progestasert IUD

20. Polymer Membrane Permeation Controlled TDDS. Drug Reservoir : dispersed on solid polymer matrix eg. polyisobutylene . Suspended in unleachable viscous liquid medium eg. Silicone fluid. Dissolved in solvent. Rate controlling Membrane : Microporous, Nonporous. Eg. Ethylene-Vinyl acetate copolymer. Adhesive Layer: Thin layer, adhesive, drug compatible, hypoallergic, eg. Silicone adhesive.

21. Polymeric Membrane Permeation Controlled Release Drug Delivery System Advantages : Less fluctuation in drug blood levels. Frequency reduction in dosing. Improved patient convenience & compliance. Increased safety margin of the high potency drugs. Reduction in total health care cost. Disadvantages : Decreased systemic availability in comparison to immediate release conventional dosage forms. Poor in vivo – in vitro correlation. Possibility of dose dumping. Retrieval of drug is difficult. Higher cost of formulation .

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