1. POLYMER SCIENCE Prof. Dr. Basavaraj K. Nanjwade M. Pharm., Ph.D By:
KLE University’s College of Pharmacy
BELGAUM , Karnataka, India
Cell:
Cell No:

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
7th Sept. 2010
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
7th Sept. 2010
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.
7th Sept. 2010
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
7th Sept. 2010
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.
7th Sept. 2010
KLECOP, Nipani 5

7. 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
7th Sept. 2010
KLECOP, Nipani 6

8. Polymers can be represented by – 3-D solid models
– 3-D space models
– 2-D models
7th Sept. 2010
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
7th Sept. 2010
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:
7th Sept. 2010
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.
7th Sept. 2010
KLECOP, Nipani 10

12. The properties of polymers depend heavily on the molecule length.
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
7th Sept. 2010
KLECOP, Nipani 11

13. Number Average Molecular Weight Mn= Σ Xi 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
7th Sept. 2010
KLECOP, Nipani 12

14. Although we often represent polymer chains as being straight,
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.
7th Sept. 2010
KLECOP, Nipani 13

15. The carbon – carbon bonds in simple polymers form angles of 109º
Contd…
The carbon – carbon bonds in simple polymers form angles of 109º
7th Sept. 2010
KLECOP, Nipani 14

16. 7th Sept. 2010
KLECOP, Nipani 15

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).
7th Sept. 2010
KLECOP, Nipani 16

18. 7th Sept. 2010
KLECOP, Nipani 17

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.
7th Sept. 2010
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
7th Sept. 2010
KLECOP, Nipani 19

21. BASED ON CHEMICAL STRUCTURE: Activated C-C Polymer
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
7th Sept. 2010
KLECOP, Nipani 20

22. BASED ON BIO-STABILITY: Bio-degradable Non Bio-degradable
Contd….
BASED ON BIO-STABILITY:
Bio-degradable
Non Bio-degradable
7th Sept. 2010
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
7th Sept. 2010
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 good drug polymer linkage
7th Sept. 2010
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
7th Sept. 2010
KLECOP, Nipani 24

26. Drug release from typical matrix release system
7th Sept. 2010
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.
7th Sept. 2010
KLECOP, Nipani 26

28.                                      Drug delivery from typical reservoir devices: (a) implantable or oral systems, and (b) transdermal systems.
7th Sept. 2010
KLECOP, Nipani 27

29. 7th Sept. 2010
KLECOP, Nipani 28

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.
7th Sept. 2010
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.
7th Sept. 2010
KLECOP, Nipani 30

32. Drug delivery from (a) reservoir and (b) matrix swelling-controlled release systems.
7th Sept. 2010
KLECOP, Nipani 31

33. Stimulus Hydrogel Mechanism Ionic hydrogel pH Acidic or basic hydrogel
Change in pH-swelling- release of drug
Ionic strength
Ionic hydrogel
Change in ionic strength change in concentration of ions inside gel change in swelling release of drug
Chemical species
Hydrogel containing electron-accepting groups
Electron-donating compounds formation of charge/transfer complex change in swelling release of drug
7th Sept. 2010
KLECOP, Nipani 32

34. Enzyme-substrate Hydrogel containing immobilized enzymes
Substrate present enzymatic conversion product changes swelling of gel release of drug
Magnetic
Magnetic particles dispersed in alginate microshperes
Applied magnetic field change in pores in gel change in swelling release of drug
Thermal
Thermoresponsive hrydrogel poly(N-isopro- pylacrylamide
Change in temperature change in polymer-polymer and water-polymer interactions change in swelling release of drug
7th Sept. 2010
KLECOP, Nipani 33

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.
07/09/2010
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
7th Sept. 2010
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
7th Sept. 2010
KLECOP, Nipani 36

38. BIO DEGARADABLE POLYMERS
7th Sept. 2010
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
7th Sept. 2010
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
7th Sept. 2010
KLECOP, Nipani 39

41. Sterilization process PHYSICOCHEMICAL FACTORS Ion exchange
CONTD
Processing condition
Annealing
Site of implantation
Sterilization process
PHYSICOCHEMICAL FACTORS
Ion exchange
Ionic strength pH
7th Sept. 2010
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
7th Sept. 2010
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
7th Sept. 2010
KLECOP, Nipani 42

44. The shape of polymer can be important in drug release kinetics.
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.
7th Sept. 2010
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
7th Sept. 2010
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
7th Sept. 2010
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.
7th Sept. 2010
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
7th Sept. 2010
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
7th Sept. 2010
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
7th Sept. 2010
KLECOP, Nipani 49

51. 7th Sept. 2010
KLECOP, Nipani 50

52. The dissolution of water-insoluble macromolecules with side groups that are converted to water-soluble polymers as a result of ionization, protonation or hydrolysis of the groups. With this mechanism the polymer does not degrade and its molecular weight remains essentially unchanged. E.g. cellulose acetate
The degradation of insoluble polymers with labile bonds. Hydrolysis of labile bonds causes scission of the polymer backbone, thereby forming low molecular weight, water-soluble molecules. E.g. poly (lactic acid), poly (glycolic acid)
The three mechanisms described are not mutually exclusive; combinations of them can occur.
7th Sept. 2010
KLECOP, Nipani 51

53. PHYSICAL EROSION
The physical erosion mechanisms can be characterized as heterogeneous or homogeneous.
In heterogeneous erosion, also called as surface erosion, the polymer erodes only at the surface, and maintains its physical integrity as it degrades. As a result drug kinetics are predictable, and zero order release kinetics can be obtained by applying the appropriate geometry. Crystalline regions exclude water. Therefore highly crystalline polymers tend to undergo heterogeneous erosion. E.g polyanhydrides
7th Sept. 2010
KLECOP, Nipani 52

54. Homogeneous erosion, means the hydrolysis occurs at even rate throughout the polymeric matrix. Generally these polymers tend to be more hydrophilic than those exhibiting surface erosion. As a result, water penetrates the polymeric matrix and increases the rate of diffusion. In homogeneous erosion, there is loss of integrity of the polymer matrix. E.g poly lactic acid
7th Sept. 2010
KLECOP, Nipani 53

55. Polymers are very common in nature
Natural polymers
Polymers are very common in nature
some of the most widespread naturally occurring substances are polymers Starch and cellulose are examples
Green plants have the ability to take the simple sugar known as glucose and make very long chains containing many glucose units
These long chains are molecules of starch or cellulose
If we assign the symbol G to stand for a glucose molecule, then starch or cellulose can be represented as:
-G-G-G-G-G-G-G-G-G-G-G-G-G-G-G-G-G-G-G-G-G-G-G-G-G-G-G-
7th Sept. 2010
KLECOP, Nipani 54

56. 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.
7th Sept. 2010
KLECOP, Nipani 55

57. - Collagen : Found from animal tissue.
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.
7th Sept. 2010
KLECOP, Nipani 56

58. - Starch : Usually derivatised by introducing acrylic
2) Polysaccharides :
- Starch : Usually derivatised by introducing acrylic
groups before manufactured int 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.
7th Sept. 2010
KLECOP, Nipani 57

59. CURRENTLY AVAILABLE POLYMERS FOR CONTROLLED RELEASE
Diffusion controlled systems
Solvent activated systems
Chemically controlled systems
Magnetically controlled systems
7th Sept. 2010
KLECOP, Nipani 58

60. DIFFUSION CONTROLLED SYSTEM
Reservoir type
Shape : spherical, cylindrical, disk-like
Core : powdered or liquid forms
Properties of the drug and the polymer : diffusion rate and release rate into the bloodstream
Problems : removal of the system, accidental rupture
Matrix type
Uniform distribution and uniform release rate
No danger of drug dumping
7th Sept. 2010
KLECOP, Nipani 59

61. SOLVENT ACTIVATED SYSTEM
Osmotically controlled system
Semipermeable membrane
Osmotic pressure decrease concentration gradient
Inward movement of fluid : out of the device through a small orifice
Swelling controlled system
Hydrophilic macromolecules cross-linked to form a three-dimensional network
Permeability for solute at a controlled rate as the polymer swells
7th Sept. 2010
KLECOP, Nipani 60

62. CHEMICALLY CONTROLLED SYSTEMS
Pendant-chain system
Drug : chemically linked to the backbone
Chemical hydrolysis or enzymatic cleavage
Linked directly or via a spacer group
Bioerodable or biodegradable system
Drug : uniformly dispersed
Slow released as the polymer disintegrates
No removal from the body
Irrespective of solubility of drug in water
   
7th Sept. 2010
KLECOP, Nipani 61

63. MAGNETICALLY CONTROLLED SYSTEMS
Cancer chemotherapy
Selective targeting of antitumor agents
Minimizing toxicity
Magnetically responsive drug carrier systems
Albumin and magnetic microspheres
High efficiency for in vivo targeting
Controllable release of drug at the microvascular level
   
7th Sept. 2010
KLECOP, Nipani 62

64. RECENTLY DEVELOPED MARKETED FORMULATIONS
Medisorb
Microencapsulation by PLA, PGA, PLGA
Drug release : week to one year
Alzamer
Bioerodible polymer : release at a controlled rate
Chronic disease, contraception, topical therapy
7th Sept. 2010
KLECOP, Nipani 63

65. USE OF FEW POLYMERS IN DRUG DELIVERY
Poly(L-lactic acid) for release of progesterone, estradiol, dexamethasone
Copolymer of gluconic acid and –ethyl-L-glutamte as bioerodible monolithic device
PLA, PGA, PLGA for parenteral administration of polypeptide
Sustained release (weeks or months)
  Orahesive® : sodium carboxymethyl cellulose, Pectin, gelatin
Orabase ® : blend in a polymethylene/mineral oil base  
7th Sept. 2010
KLECOP, Nipani 64

66. Novel drug delivery systems – Y.W.Chien – Dekker 50
REFERENCES
Novel drug delivery systems – Y.W.Chien – Dekker 50
Bio–adhesive drug delivery system –
Dekker 98
Encyclopedia of controlled drug delivery systems.
7th Sept. 2010
KLECOP, Nipani 65

67. ANY QUERIES?
7th Sept. 2010
KLECOP, Nipani 66

68. Y O U T H A N K Cell No: 00919742431000 E-mail:bknanjwade@yahoo.co.in
7th Sept. 2010
KLECOP, Nipani 67