1. By : Prof. Dr. Basavaraj K. Nanjwade M. Pharm., Ph. D KLE University’s College of Pharmacy BELGAUM – 590010, Karnataka, India Cell No: 00919742431000 E-mail: bknanjwade@yahoo.co.in

2. 07/09/2010KLE COP, Nipani2 CONTENTS oIntroduction oClassification of Polymers oApplications in Conventional Dosage Forms oApplications in Controlled Drug Delivery oBiodegradable Polymers oNatural Polymers oReferences

3. 07/09/2010KLE COP, Nipani3 INTRODUCTION Polymers are used extensively in our daily routine life. In pharmaceutical preparations also they have several applications e.g. In mfg of bottles, syringes, vials, cathaters, and also in drug formulations.

4. 07/09/2010KLE COP, Nipani4 What is Polymer? “Polymer” word is derived from Greek roots “Poly” meaning many and “Meros” meaning parts. Definition : Polymers are long chain organic molecules assembled from many smaller molecules called as monomers.

5. 07/09/2010KLE COP, Nipani5 Copolymer : Polymers formed from two or more different monomers are called as copolymers. - [A – B – A – B – A – B] – Homopolymer : Polymers formed from bonding of identical monomers are called as homopolymers. - [A – A – A – A – A] -

6. 07/09/2010KLE COP, Nipani6 A. Based on origin : a) Natural Polymers : e.g. Proteins – Collagen, Keratin, Albumin Carbohydrates – starch, cellulose, glycogen. DNA, RNA b)Synthetic Polymers : e.g. polyesters, polyanhydrides, polyamides. B. Based on Bio-stability : a)Bio-degradable Polymers : e.g. polyesters, proteins, carbohydrates, etc b)Non – biodegradable Polymers : e.g. ethyl cellulose, HPMC, acrylic polymers, silicones. CLASSIFICATION

7. 07/09/2010KLE COP, Nipani7 C. Based on Reaction mode of Polymerization : a) Addition Polymers : Here, the monomer molecules bond to each other without the loss of any other atoms. e.g. Alkene monomers b) Condensation Polymers : Usually two different monomers combine with the loss of small molecule, usually water. e.g. polyesters, polyamides.

8. 07/09/2010KLE COP, Nipani8 D. Based on Interaction with Water : a) Non – biodegradable Hydrophobic Polymers : These are inert compounds and are eliminated intact from the site of application. e.g. polyethylene – vinyl acetate, polyvinyl chloride. b) Hydrogels : They swell but do not dissolve when brought in contact with water. e.g. polyvinyl pyrrolidone c) Soluble Polymers : These are moderate mol. wt uncross-linked polymers that dissolve in water. e.g. HPMC, PEG d) Biodegradable Polymers : These slowly disappear from the site of administration in response to a chemical reaction such as hydrolysis. e.g. Polyacrylic acid. Polyglycolic acid.

9. 07/09/2010KLE COP, Nipani9 CHARACTERISTICS OF IDEAL POLYMER Should be inert and compatible with the environment. Should be non-toxic. Should be easily administered. Should be easy and inexpensive to fabricate. Should have good mechanical strength.

10. 07/09/2010KLE COP, Nipani10 Criteria Followed In Polymer Selection It must be soluble and easy to synthesize; must have a finite molecular wt. Should provide drug attachment and release sites for drug polymer linkages. Should be compatible with biological environment, i.e. non-toxic and non- antigenic. Should be biodegradable or be eliminated from body after its function is over.

11. 07/09/2010KLE COP, Nipani11 Applications in Conventional Dosage Forms Tablets : - As binders - To mask unpleasant taste - For enteric coated tablets Liquids : - Viscosity enhancers - For controlling the flow Semisolids : - In the gel preparation - In ointments In transdermal Patches

12. 07/09/2010KLE COP, Nipani12 Applications In Controlled Drug Delivery Applications In Controlled Drug Delivery Reservoir Systems - Ocusert System - Progestasert System - Reservoir Designed Transdermal Patches Matrix Systems Swelling Controlled Release Systems Biodegradable Systems Osmotically controlled Drug Delivery

13. 07/09/2010KLE COP, Nipani13 A. Reservoir System :  Ocusert System : - Novel means of controlled ocular drug delivery - Used for max 7 days treatment of Glaucoma - Consists of core reservoir of pilocarpine & alginic acid sandwiched between two sheets of transparent, lipophillic, rate controlling membrane of ethylene-vinyl acetate copolymer. - Inserted in cul-de-sac, lachrymal fluid enters the system and the dissolved drug slowly gets released through polymeric membrane.

14. 07/09/2010KLE COP, Nipani14  Progestasert system : - Used for once-a-year contraception - Consists of drug saturated liquid medium encapsulated in a polymeric membrane. - Progesterone is released at a constant rate of 65 µg/day. - Polymers used are : Silicone elastomers, polyethylene, ethylene-vinyl acetate.

15. 07/09/2010KLE COP, Nipani15

16. 07/09/2010KLE COP, Nipani16  Transdermal Patches : - Drug is sandwiched between drug impermeable backing and drug permeable rate controlling polymer. e.g. Ethylene-vinyl acetate copolymer - In the reservoir, drug is dispersed in solid polymer matrix. e.g. Polyisobutylene - On the external surface, there should be adhesive polymer. e.g. Silicone Polymer, Polyacrylates.

17. 07/09/2010KLE COP, Nipani17 Transdermal Controlled Drug Delivery

18. 07/09/2010KLE COP, Nipani18 B. Osmotically Controlled Drug Delivery System Drug is coated with semi- permeable polymer e.g. Cellulose acetate. Water generates osmotic pressure gradient by permeating through semi- permeable membrane. Due to that drug pumps out of delivery orifice over a prolonged time at a defined rate.

19. 07/09/2010KLE COP, Nipani19 C. Biodegradable System Mainly used for parenteral controlled drug delivery. Drug is encapsulated in biodegradable microcapsules which are suspended in aqueous / oleaginous medium and injected subcutaneously or intra-muscularly. Polymers used for microcapsules are : Gelatin, dextran, polylactate, lactide – glycolide copolymer. The release of drug is controlled by the rate of bio-degradation of polymer.

20. 07/09/2010KLE COP, Nipani20 D. Matrix Systems Drug particles are enclosed in a matrix environment formed by cross-linking of polymer chains. For the drug to get released, it has to be first dissolved in surrounding polymer and then diffuse through the polymer structure. Polymers used are : polyalkyls, polyvinyls, etc. Example – Nitroglycerine releasing system for prophylaxis or treatment of angina pectoris.

21. 07/09/2010KLE COP, Nipani21 E. Swelling Controlled Release Systems Drug is enclosed in a collapsible drug compartment inside a rigid, shape-retaining housing. The shape between external housing and drug compartment contains laminate of swellable, hydrophillic cross-linked polymer. e.g. polyhydroxyalkyl methacrylate. This polymer absorbs GI fluid through annular openings in the bottom of housing.

22. 07/09/2010KLE COP, Nipani22 Because of this, laminate swells and generates hydrodynamic pressure and induces the delivery of drug formulation through the orifice. Because of this, laminate swells and generates hydrodynamic pressure and induces the delivery of drug formulation through the orifice. Drug delivery orifice Shape retaining housing Collapsible drug container Swellable polymer Liquid drug formulation Annular openings

23. 07/09/2010KLE COP, Nipani23 Biodegradable Polymers Definition : Biodegradable polymers are defined as polymers comprised of monomers linked to one another through functional groups and have unstable links in the backbone. They slowly disappear from the site of administration in response to a chemical reaction such as hydrolysis.

24. 07/09/2010KLE COP, Nipani24  Classification : Synthetic Polymers : a) Aliphatic polymers b) Polyphospho-esters c) Polyanhydrides d) Polyorthoesters Natural Polymers : a) Collagen b) Albumin c) Casein d) gelatin Environment Responsive Polymers : a) Thermo sensitive – Poly acryl amide b) pH sensitive – Methyl vinyl ether

25. 07/09/2010KLE COP, Nipani25 Mechanism of Biodegradation A. Hydrolytic Degradation : Breakdown of polymer by water by cleaving long chain into monomeric acids. This is done by two ways : Bulk eroding polymers e.g. Polylactic acid (PLA) Polyglycolic acid (PGA)

26. 07/09/2010KLE COP, Nipani26 Surface Eroding Polymers : e.g. Polyanhydrides B. Enzymatic Degradation : Exact mechanism is not known but may be due to lysis of long polymer chain by attaching to it.

27. 07/09/2010KLE COP, Nipani27 Factors affecting Biodegradation : - Polymer morphology - pH & ionic strength - Drug – polymer interaction - Chemical composition and structure Applications : - Sutures used during the surgery - For orthopaedic applications - For tissue regeneration - For protein drug delivery

28. 07/09/2010KLE COP, Nipani28 A NEW BIODEGRADABLE POLYMER POLYKETAL Advantages over existing biodegradable polymers : Is biodegradable in FDA approved compounds. Synthesis is easy Degradation does not produce inflammation caused by acid produced. Quick degradation (within a week) Applications : 1. Delivery of anti – oxidants in acute liver failure 2. In any protein based vaccine.

29. 07/09/2010KLE COP, Nipani29 Natural Polymers Natural polymers remains the primary choice of formulator because - They are natural products of living organism - Readily available - Relatively inexpensive - Capable of chemical modification Moreover, it satisfies most of the ideal requirements of polymers. But the only and major difficulty is the batch- to-batch reproducibility and purity of the sample.

30. 07/09/2010KLE COP, Nipani30 Examples : 1) Proteins : - Collagen : Found from animal tissue. Used in absorbable sutures, sponge wound dressing, as drug delivery vehicles - Albumin : Obtained by fabrication of blood from healthy donor. Used as carriers in nanocapsules & microspheres - Gelatin : A natural water soluble polymer Used in capsule shells and also as coating material in microencapsulation.

31. 07/09/2010KLE COP, Nipani31 2) Polysaccharides : - Starch : Usually derivatised by introducing acrylic groups before manufactured into microspheres. Also used as binders. - Cellulose : Naturally occuring linear polysaccharide. It is insoluble in water but solubility can be obtained by substituting -OH group. Na-CMC is used as thickner, suspending agent, and film formers. 3) DNA &RNA : They are the structural unit of our body. DNA is the blueprint that determines everything of our body.

32. 07/09/2010KLE COP, Nipani32 Polysaccharide hydrogels for modified release formulations. Hydrogels are three-dimensional, hydrophilic, polymeric networks, with chemical or physical cross-links, capable of imbibing large amounts of water or biological fluids. Among the numerous macromolecules that can be used for hydrogel formation, polysaccharides are extremely advantageous compared to synthetic polymers

33. 07/09/2010KLE COP, Nipani33 Biodegradable dextran hydrogels for protein delivery applications Hydrogels offer good opportunities as protein drug delivery due to its inherent biocompatibility. It guarantees safe and controlled delivery of proteinacious drugs. Dextran is a natural polysaccharide and offers good properties to be used in hydrogel system. Here, special attention is given to network properties, protein delivery, degradation behavior and biocompatibility.

34. 07/09/2010KLE COP, Nipani34 Muco–Adhesive Polymers These polymers have carried major attention recently for the role they may play in following features of controlled drug delivery: Prolonged residence time at absorption site. e.g. by controlling GI transit, for transnasal drug delivery. Localization of drug in specified regions to improve the bioavailability. e.g. targetting to the colon.  Examples : Polyacrylates, Chitosans, Polyglucan derivatives.

35. 07/09/2010KLE COP, Nipani35 REFERENCES Novel drug delivery systems – Y.W.Chien – Dekker 50 Eastern Pharmacist – April, 2001. August, 1998 Bio–adhesive drug delivery system – Dekker 98 Encyclopedia of controlled drug delivery systems.

36. 07/09/2010KLE COP, Nipani36 Cell No: 00919742431000 E-mail: bknanjwade@yahoo.co.in