POLYMER SCIENCE

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

2. CONTENTS • INTRODUCTION TO POLYMERS • CLASSIFICATION OF POLYMERS • GENERAL MECHANISM OF DRUG RELEASE • APPLICATION IN CONVENTIONAL DOSGAE FORMS • APPLICATIONS IN CONTROLLED DRUG DELIVERY • BIODEGRADABLE POLYMERS • NATURAL POLYMERS • REFERENCESS KLECOP, Nipani 1

3. INTRODUCTION A polymer is a very large molecule in which one or two small units is repeated over and over again The small repeating units are known as monomers Imagine that a monomer can be represented by the letter A. Then a polymer made of that monomer would have the structure: -A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A-A KLECOP, Nipani 2

4. In another kind of polymer, two different monomers might be involved If the letters A and B represent those monomers, then the polymer could be represented as: -A-B-A-B-A-B-A-B-A-B-A-B-A-B-A-B-A-B-A-B-A-B-A-B-A-B-A A polymer with two different monomers is known as a copolymer. KLECOP, Nipani 3

5. Chemistry of the polymers • Polymers are organic, chain molecules • They can, vary from a few hundreds to thousands of atoms long. • There are three classes of polymers that we will consider:- • Thermo-plastic - Flexible linear chains • Thermosetting - Rigid 3-D network • Elastomeric - Linear cross-linked chains KLECOP, Nipani 4

6. THERMOPLASTICS • In simple thermoplastic polymers, the chains are bound to each other by weaker Van der Waal’s forces and mechanical entanglement. • Therefore, the chains are relatively strong, but it is relatively easy to slide and rotate the chains over each other. KLECOP, Nipani 5

7. ELASTOMERS • Common elastomers are made from highly coiled, linear polymer chains. • In their natural condition, elastomers behave in a similar manner to thermoplastics (viscoelastic) – i.e. applying a force causes the chains to uncoil and stretch, but they also slide past each other causing permanent deformation. • This can be prevented by cross-linking the polymer chains KLECOP, Nipani 6

8. Polymers can be represented by • – 3-D solid models • – 3-D space models • – 2-D models KLECOP, Nipani 7

9. MOLECULAR STRUCTURE • The mechanical properties are also governed by the structure of the polymer chains. • They can be: Linear Network (3D) Branched Cross-linked KLECOP, Nipani 8

10. POLYMER MOLECULES • Before we discuss how the polymer chain molecules are formed, we need to cover some definitions: • The ethylene monomer looks like • The polyethylene molecule looks like: KLECOP, Nipani 9

11. Polyethylene is built up from repeat units or mers. • Ethylene has an unsaturated bond. (the double bond can be broken to form two single bonds) • The functionality of a repeat unit is the number of sites at which new molecules can be attached. KLECOP, Nipani 10

12. MOLECULAR WEIGHT • When polymers are fabricated, there will always be a distribution of chain lengths. • The properties of polymers depend heavily on the molecule length. • There are two ways to calculate the average molecular weight: 1 Number Average Molecular Weight 2. Weight Average Molecular Weight KLECOP, Nipani 11

13. Number Average Molecular Weight Mn= ΣXi Mi Where, xi = number of chains in the ith weight range Mi = the middle of the ith weight range • Weight Average Molecular Weight Mw = Σ Wi Mi Where, wi = weight fraction of chains in the ith range Mi = the middle of the ith weight range KLECOP, Nipani 12

14. MOLECULAR SHAPE • The mechanical properties of a polymer are dictated in part by the shape of the chain. • Although we often represent polymer chains as being straight, • They rarely are. KLECOP, Nipani 13

15. Contd… • The carbon – carbon bonds in simple polymers form angles of 109º KLECOP, Nipani 14

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17. POLYMER CRYSTALLINITY • Thermoplastic polymers go through a series of changes with changes in temperature. (Similar to ceramic glasses) • In their solid form they can be semi-crystalline or amorphous (glassy). KLECOP, Nipani 16

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19. CRYSTALLINE THERMOPLASTIC • The ability of a polymer to crystallize is affected by: • Complexity of the chain: Crystallization is easiest for simple polymers (e.g. polyethylene) and harder for complex polymers (e.g. with large side groups, branches, etc.) • Cooling rate: Slow cooling allows more time for the chains to align • Annealing: Heating to just below the melting temperature can allow chains to align and form crystals • Degree of Polymerization: It is harder to crystallize longer chains 5.Deformation: Slow deformation between Tg and Tm can straighten the chains allowing them to get closer together. KLECOP, Nipani 18

20. CLASSIFICATION POLYMERS: • ON BASIS OF INTERACTION WITH WATER: • Non-biodegradable hydrophobic Polymers E.g. polyvinyl chloride, polyethylene vinyl acetate • Soluble Polymers E.g. HPMC, PEG • Hydrogels E.g. Polyvinyl pyrrolidine • BASED ON POLYMERISATION METHOD: • Addition Polymers E.g. Alkane Polymers • Condensation polymers E.g. Polysterene and Polyamide • Rearrangement polymers • BASED ON POLYMERIZATION MECHANISM: • Chain Polymerization • Step growth Polymerization KLECOP, Nipani 19

21. Contd…. • BASED ON CHEMICAL STRUCTURE: • Activated C-C Polymer • Polyamides, polyurethanes • Polyesters, polycarbonates • Polyacetals, Polyketals, Polyorthoesters • Inorganic polymers • Natural polymers • BASED ON OCCURRENCE: • Natural polymers E.g. 1. Proteins-collagen, keratin, albumin, 2. carbohydrates- starch, cellulose • Synthetic polymers E.g. Polyesters, polyamides KLECOP, Nipani 20

22. Contd…. • BASED ON BIO-STABILITY: • Bio-degradable • Non Bio-degradable KLECOP, Nipani 21

23. CHARACTERISTICS OF AN IDEAL POLYMER • Should be versatile and possess a wide range of mechanical, physical, chemical properties • Should be non-toxic and have good mechanical strength and should be easily administered • Should be inexpensive • Should be easy to fabricate • Should be inert to host tissue and compatible with environment KLECOP, Nipani 22

24. CRITERIA FOLLOWED IN POLYMER SELECTION • The polymer should be soluble and easy to synthesis • It should have finite molecular weight • It should be compatible with biological environment • It should be biodegradable • It should provide gooddrug polymer linkage KLECOP, Nipani 23

25. GENERAL MECHANISM OF DRUG RELEASE FROM POLYMER • There are three primary mechanisms by which active agents can be released from a delivery system: namely, • Diffusion, degradation, and swelling followed by diffusion • Any or all of these mechanisms may occur in a given release system • Diffusion occurs when a drug or other active agent passes through the polymer that forms the controlled-release device. The diffusion can occur on a macroscopic scale as through pores in the polymer matrix or on a molecular level, by passing between polymer chains KLECOP, Nipani 24

26. Drug release from typical matrix release system KLECOP, Nipani 25

27. For the reservoir systems the drug delivery rate can remain fairly constant. • In this design, a reservoir whether solid drug, dilute solution, or highly concentrated drug solution within a polymer matrix is surrounded by a film or membrane of a rate-controlling material. • The only structure effectively limiting the release of the drug is the polymer layer surrounding the reservoir. • This polymer coating is uniform and of a nonchanging thickness, the diffusion rate of the active agent can be kept fairly stable throughout the lifetime of the delivery system. The system shown in Figure a is representative of an implantable or oral reservoir delivery system, whereas the system shown in b. KLECOP, Nipani 26

28. Drug delivery from typical reservoir devices: (a) implantable or oral systems, and (b) transdermal systems. KLECOP, Nipani 27

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30. ENVIRONMENTALLY RESPONSIVE SYSTEM • It is also possible for a drug delivery system to be designed so that it is incapable of releasing its agent or agents until it is placed in an appropriate biological environment. • Controlled release systems are initially dry and, when placed in the body, will absorb water or other body fluids and swell, • The swelling increases the aqueous solvent content within the formulation as well as the polymer mesh size, enabling the drug to diffuse through the swollen network into the external environment. KLECOP, Nipani 29

31. Examples of these types of devices are shown in Figures a and b for reservoir and matrix systems. • Most of the materials used in swelling-controlled release systems are based on hydrogels, which are polymers that will swell without dissolving when placed in water or other biological fluids. These hydrogels can absorb a great deal of fluid and, at equilibrium, typically comprise 60–90% fluid and only 10–30% polymer. KLECOP, Nipani 30

32. Drug delivery from (a) reservoir and (b) matrix swelling-controlled release systems. KLECOP, Nipani 31

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35. APPLICATIONS • The pharmaceutical applications of polymers range from their use as binders in tablets • Viscosity and flow controlling agents in liquids, suspensions and emulsions • Polymers are also used as film coatings to disguise the unpleasant taste of a drug, to enhance drug stability and to modify drug release characteristics. KLECOP, Nipani 34

36. 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 KLECOP, Nipani 35

37. 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 KLECOP, Nipani 36

38. BIO DEGARADABLE POLYMERS KLECOP, Nipani 37

39. BIO DEGRADABLE POLYMER • Biodegradable polymers can be classified in two: • Natural biodegradable polymer • Synthetic biodegradable polymer • Synthetic biodegradable polymer are preferred more than the natural biodegradable polymer because they are free of immunogenicity & their physicochemical properties are more predictable &reproducible KLECOP, Nipani 38

40. FACTORS AFFECTING BIODEGRADATION OF POLYMERS • PHYSICAL FACTORS • Shape & size • Variation of diffusion coefficient • Mechanical stresses • CHEMICAL FACTORS • Chemical structure & composition • Presence of ionic group • Distribution of repeat units in multimers • configuration structure • Molecular weight • Morphology • Presence of low molecular weight compounds KLECOP, Nipani 39

41. CONTD • Processing condition • Annealing • Site of implantation • Sterilization process • PHYSICOCHEMICAL FACTORS • Ion exchange • Ionic strength • pH KLECOP, Nipani 40

42. ADVANTAGES OF BIODEGRADABLE POLYMERS IN DRUG DELEVERY • Localized delivery of drug • Sustained delivery of drug • Stabilization of drug • Decrease in dosing frequency • Reduce side effects • Improved patient compliance • Controllable degradation rate KLECOP, Nipani 41

43. ROLE OF POLYMER IN DRUG DELIVERY The polymer can protect the drug from the physiological environment & hence improve its stability in vivo. Most biodegradable polymer are designed to degrade within the body as a result of hydrolysis of polymer chain into biologically acceptable & progressively small compounds. TYPES OF POLYMER DRUG DELIVERY SYSTEM: MICRO PARTICLES: These have been used to deliver therapeutic agents like doxycycline. NANO PARTICLES: delivery drugs like doxorubicin, cyclosporine, paclitaxel, 5- fluorouracil etc KLECOP, Nipani 42

44. POLYMERIC MICELLES: used to deliver therapeutic agents. • HYDRO GELS: these are currently studies as controlled release carriers of proteins & peptides. • POLYMER MORPHOLOGY: The polymer matrix can be formulated as either micro/nano-spheres, gel, film or an extruded shape. The shape of polymer can be important in drug release kinetics. KLECOP, Nipani 43

45. Application • For specific site drug delivery- anti tumour agent • Polymer system for gene therapy • Bio degradable polymer for ocular, non- viral DNA, tissue engineering, vascular, orthopaedic, skin adhesive & surgical glues. • Bio degradable drug system for therapeutic agents such as anti tumor, antipsychotic agent, anti-inflammatory agent and biomacro molecules such as proteins, peptides and nucleic acids KLECOP, Nipani 44

46. BIO DEGRADABLE POLYMERS FOR ADVANCE DRUG DELIVERY • Polymers play an vital role in both conventional as well as novel drug delivery. Among them , the use of bio degradable polymer has been success fully carried out. • Early studies on the use of biodegradable suture demonstrated that these polymers were non- toxic & biodegradable. • By incorporating drug into biodegradable polymer whether natural or synthetic, dosage forms that release the drug in predesigned manner over prolong time KLECOP, Nipani 45

47. DRUG RELEASE MECHANISM • The release of drugs from the erodible polymers occurs basically by three mechanisms, • The drug is attached to the polymeric backbone by a labile bond, this bond has a higher reactivity toward hydrolysis than the polymer reactivity to break down. • The drug is in the core surrounded by a biodegradable rate controlling membrane. This is a reservoir type device that provides erodibility to eliminate surgical removal of the drug-depleted device. • a homogeneously dispersed drug in the biodegradable polymer. The drug is released by erosion, diffusion, or a combination of both. KLECOP, Nipani 46

48. Schematic representation of drug release mechanisms In mechanism 1, drug is released by hydrolysis of polymeric bond. In mechanism 2, drug release is controlled by biodegradable membrane. In mechanism 3, drug is released by erosion, diffusion, or a combination of both KLECOP, Nipani 47

49. POLYMER EROSION MECHANISM • The term 'biodegradation' is limited to the description of chemical processes (chemical changes that alter either the molecular weight or solubility of the polymer) • ‘Bioerosion' may be restricted to refer to physical processes that result in weight loss of a polymer device. • The erosion of polymers basically takes place by two methods:- • Chemical erosion • Physical erosion KLECOP, Nipani 48

50. CHEMICAL EROSION • There are three general chemical mechanisms that cause bioerosion • The degradation of water-soluble macromolecules that are crosslinked to form three-dimensional network. As long as crosslinks remain intact, the network is intact and is insoluble. Degradation in these systems can occur either at crosslinks to form soluble backbone polymeric chains (type IA) or at the main chain to form water-soluble fragments (type IB). Generally, degradation of type IA polymers provide high molecular weight, water-soluble fragments, while degradation of type IB polymers provide low molecular weight, water soluble oligomers and monomers KLECOP, Nipani 49