1、By : Prof. Dr. Basavaraj K. Nanjwade M. Pharm., Ph. D KLE Universitys College of Pharmacy BELGAUM 590010, Karnataka, India Cell No: 00919742431000 E-mail: bknanjwadeyahoo.co.in,POLYMER SCIENCE,07/09/2010,KLE COP, Nipani,2,CONTENTS,Introduction Classification of Polymers Applications in Conventional
2、Dosage Forms Applications in Controlled Drug Delivery Biodegradable Polymers Natural Polymers References,07/09/2010,KLE COP, Nipani,3,INTRODUCTION,Polymers are used extensively in our daily routine life. In pharmaceutical preparations also they have several applicationse.g. In mfg of bottles, syring
3、es, vials, cathaters, and also in drug formulations.,07/09/2010,KLE COP, Nipani,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
4、.,07/09/2010,KLE COP, Nipani,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 -,07/09/2010,KLE COP, Nipani,6,A. Based on origin :a) Natural Po
5、lymers :e.g. Proteins Collagen, Keratin, AlbuminCarbohydrates 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, etcb) Non biodegradable Polymers :e.g.
6、ethyl cellulose, HPMC, acrylic polymers, silicones.,CLASSIFICATION,07/09/2010,KLE COP, Nipani,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 monomersb) Condensation Polymers :Usually
7、two different monomers combine with the loss of small molecule, usually water. e.g. polyesters, polyamides.,07/09/2010,KLE COP, Nipani,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
8、. polyethylene vinyl acetate, polyvinyl chloride.b) Hydrogels :They swell but do not dissolve when brought in contact with water.e.g. polyvinyl pyrrolidonec) Soluble Polymers :These are moderate mol. wt uncross-linked polymers that dissolve in water.e.g. HPMC, PEGd) Biodegradable Polymers :These slo
9、wly disappear from the site of administration in response to a chemical reaction such as hydrolysis.e.g. Polyacrylic acid. Polyglycolic acid.,07/09/2010,KLE COP, Nipani,9,CHARACTERISTICS OF IDEAL POLYMER,Should be inert and compatible with the environment. Should be non-toxic. Should be easily admin
10、istered. Should be easy and inexpensive to fabricate. Should have good mechanical strength.,07/09/2010,KLE COP, Nipani,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 polym
11、er 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.,07/09/2010,KLE COP, Nipani,11,Applications in Conventional Dosage Forms,Tablets : - As binders- To mask unpleasant taste- Fo
12、r enteric coated tablets Liquids :- Viscosity enhancers- For controlling the flow Semisolids :- In the gel preparation- In ointments In transdermal Patches,07/09/2010,KLE COP, Nipani,12,Applications In Controlled Drug Delivery,Reservoir Systems- Ocusert System- Progestasert System- Reservoir Designe
13、d Transdermal Patches Matrix Systems Swelling Controlled Release Systems Biodegradable Systems Osmotically controlled Drug Delivery,07/09/2010,KLE COP, Nipani,13,A. Reservoir System : Ocusert System : - Novel means of controlled ocular drug delivery- Used for max 7 days treatment of Glaucoma- Consis
14、ts 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 membra
15、ne.,07/09/2010,KLE COP, Nipani,14,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 g/day.- Polymers used are :Silicone elastomers, polyethylene, ethylene-vinyl
16、acetate.,07/09/2010,KLE COP, Nipani,15,07/09/2010,KLE COP, Nipani,16,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. Polyisob
17、utylene- On the external surface, there should be adhesive polymer.e.g. Silicone Polymer, Polyacrylates.,07/09/2010,KLE COP, Nipani,17,Transdermal Controlled Drug Delivery,Transdermal Controlled Drug Delivery,07/09/2010,KLE COP, Nipani,18,B. Osmotically Controlled Drug Delivery System,Drug is coated
18、 with semi-permeable polymere.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.,07/09/2010,KLE COP, Nipani,19,C. Biodegradable System,Mainly used for p
19、arenteral 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
20、 drug is controlled by the rate of bio-degradation of polymer.,07/09/2010,KLE COP, Nipani,20,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 dif
21、fuse through the polymer structure. Polymers used are :polyalkyls, polyvinyls, etc. Example Nitroglycerine releasing system for prophylaxis or treatment of angina pectoris.,07/09/2010,KLE COP, Nipani,21,E. Swelling Controlled Release Systems,Drug is enclosed in a collapsible drug compartment inside
22、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.,07/09/2010,KLE COP, Nipani,
23、22,Because of this, laminate swells and generates hydrodynamic pressure and induces the delivery of drug formulation through the orifice.,Drug delivery orificeShape retaining housingCollapsible drug containerSwellable polymerLiquid drug formulationAnnular openings,07/09/2010,KLE COP, Nipani,23,Biode
24、gradable 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.,07/0
25、9/2010,KLE COP, Nipani,24,Classification :,Synthetic Polymers :a) Aliphatic polymersb) Polyphospho-estersc) Polyanhydridesd) Polyorthoesters Natural Polymers :a) Collagenb) Albuminc) Caseind) gelatin Environment Responsive Polymers :a) Thermo sensitive Poly acryl amideb) pH sensitive Methyl vinyl et
26、her,07/09/2010,KLE COP, Nipani,25,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 polymerse.g. Polylactic acid (PLA)Polyglycolic acid (PGA),07/09/2010,KLE COP, Nipani,26,Surface
27、Eroding Polymers :e.g. PolyanhydridesB. Enzymatic Degradation :Exact mechanism is not known but may be due to lysis of long polymer chain by attaching to it.,07/09/2010,KLE COP, Nipani,27,Factors affecting Biodegradation :- Polymer morphology- pH & ionic strength- Drug polymer interaction- Chemical
28、composition and structureApplications :- Sutures used during the surgery- For orthopaedic applications- For tissue regeneration- For protein drug delivery,07/09/2010,KLE COP, Nipani,28,A NEW BIODEGRADABLE POLYMER POLYKETAL,Advantages over existing biodegradable polymers : Is biodegradable in FDA app
29、roved 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 failure2. In any protein based vaccine.,07/09/2010,KLE COP, Nipani,29,Natural Polymers,Natural polymers re
30、mains 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 reprod
31、ucibility and purity of the sample.,07/09/2010,KLE COP, Nipani,30,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
32、& microspheres- Gelatin : A natural water soluble polymerUsed in capsule shells and also as coating material in microencapsulation.,07/09/2010,KLE COP, Nipani,31,2) Polysaccharides :- Starch : Usually derivatised by introducing acrylic groups before manufactured into microspheres.Also used as binder
33、s.- 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 every
34、thing of our body.,07/09/2010,KLE COP, Nipani,32,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 ma
35、cromolecules that can be used for hydrogel formation, polysaccharides are extremely advantageous compared to synthetic polymers,07/09/2010,KLE COP, Nipani,33,Biodegradable dextran hydrogels for protein delivery applications Hydrogels offer good opportunities as protein drug delivery due to its inher
36、ent 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.,
37、07/09/2010,KLE COP, Nipani,34,MucoAdhesive 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
38、 of drug in specified regions to improve the bioavailability.e.g. targetting to the colon.Examples : Polyacrylates, Chitosans, Polyglucan derivatives.,07/09/2010,KLE COP, Nipani,35,REFERENCES,Novel drug delivery systems Y.W.Chien Dekker 50 Eastern Pharmacist April, 2001.August, 1998 Bioadhesive drug delivery system Dekker 98 Encyclopedia of controlled drug delivery systems.,07/09/2010,KLE COP, Nipani,36,THANK YOU,Cell No: 00919742431000 E-mail: bknanjwadeyahoo.co.in,
