By : Prof. Dr. firyal m. a. Al-salami Al- mustansiriyah University College of science

1. POLYMER SCIENCE By : Prof. Dr. firyal m. a. Al-salami Al-mustansiriyah University College of science Dep. Of chemistry.

2. CONTENTS • Introduction • Classification of Polymers • Applications in Conventional Dosage Forms • Applications in Controlled Drug Delivery • Biodegradable Polymers • Natural Polymers • References

3. INTRODUCTION Polymers are used extensively in our daily routine life. In pharmaceutical preparations also theyhave several applications e.g. In mfg of bottles, syringes, vials, catheters', and also in drug formulations.

4. 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. 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. CLASSIFICATION A. Based on origin : a) Natural Polymers : e.g. Proteins – Collagen, Keratin, Albumin Carbohydrates – starch, cellulose, glycogen. DNA, RNA • 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.

7. 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. 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. 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. 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. 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. 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. 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. Maximum desired level Drug level Minimum effective level Time Dose Maximum desired level Drug level Minimum effective level Time Dose Drug level in blood with traditional drug dosing Drug level in blood with controlled delivery dosing

15. Drug carriers The main reason for the development of these “polymeric-drug carriers” is to obtain desirable properties such as sustained therapy, slow drug release, prolonged activity, as well as decreased drug metabolism and excretion.

16. Advantages of drug carrier polymer system - Advantages of drug carrier polymer systems [159-160] 1. The action of polymeric drugs in vivo usually depends on hydrolytic or enzymatic cleavage of the drug moiety from the polymer, this give advantage of delayed and sustained release of drug over longer of time with corresponding decrease in side effects. 2. It is potentially possible to make a polymer drug with a specific required solubility rate of diffusion and increased or decreased activity by the appropriate choice of the polymer and the drug. These include situation requiring the slow release of water-soluble drugs, the fast release of low solubility drugs. 3. The coupling of two or more drugs onto the same polymer to achieve enhanced or synergistic activity. 4. The ability to synthesize polymer-drug capable of getting to a specific organ (via specific homing or affinity group) in the desired amount at the desired time. 5. It is possible to synthesize polymer drug with negligible absorpitivity for situation where localized drug action is desired (skin treatment) .

17. 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.

18. Transdermal Controlled Drug Delivery Transdermal Controlled Drug Delivery

19. First Line:A- Modification of polyvinylpyrrolidinone with amino antibiotics

20. B- Modification of polyvinylpyrrolidinone with hydroxyl compounds

21. Second Line: A- Synthesis of poly[N-substituted acrylamides]

22. B – Synthesis of poly[substituted acrylate]

23. Third Line: A – Synthesis of N-[substituted maleamic] Polymers

24. D- Preparation of citriconic acid with hydroxy drugs

25. E- Synthesis of N-substituted methyl nadamic acid

26. Fourth Line: Polycondensation of aminocacids with antibiotics

27. 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.

28. 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.

29. 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.

30. 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.

31. 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

32. 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.

33. 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

34. 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)

35. 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.

36. 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

37. 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.

38. 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.

39. 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.

40. 2) Polysaccharides : - Starch : Usually derivatised by introducing acrylic groups before manufactured into microspheres. Also used as binders. - Cellulose : Naturally occurring linear polysaccharide. It is insoluble in water but solubility can be obtained by substituting -OH group. Na-CMC is used as thickener, 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.

41. 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

42. 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.

43. 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.

44. REFERENCES SYNTHESIS AND STUDY OF SOME NOVEL POLYMERS CONTAINING DIFFERENT DRUG SUBSTITUTED GROUPS. - KHUDHEYER JAWAD KADEM ,PHD. THESIS, BABYLON UNIVERSITY ,2012. Novel drug delivery systems – Y.W.Chien – Dekker 50 Eastern Pharmacist – April, 2001. Bio–adhesive drug delivery system – Dekker 98 Encyclopedia of controlled drug delivery systems. August, 1998

45. Thank you for listening me………