Prof. Dr. Basavaraj K. Nanjwade M. Pharm., Ph. D

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POLYMER SCIENCE

• By
• Prof. Dr. Basavaraj K. Nanjwade M. Pharm., Ph. D
• KLE Universitys College of Pharmacy
• BELGAUM 590010, Karnataka, India
• Cell No 00919742431000
• E-mail bknanjwade_at_yahoo.co.in

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CONTENTS

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

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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.

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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.

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• 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 -

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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.

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• 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.

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• 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.

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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.

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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.

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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

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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

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• 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.

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• 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.

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• 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.

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Transdermal Controlled Drug Delivery
Transdermal Controlled Drug Delivery
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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.

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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.

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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.

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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.

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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

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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.

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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

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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)

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• 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.

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• 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

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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.

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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.

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• 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.

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• 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.

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• 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

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• 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.

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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 of drug in specified regions to
  improve the bioavailability.
• e.g. targetting to the colon.
• Examples Polyacrylates, Chitosans, Polyglucan
  derivatives.

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REFERENCES

• Novel drug delivery systems Y.W.Chien Dekker
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• Eastern Pharmacist April, 2001.
• August, 1998
• Bioadhesive drug delivery system
• Dekker 98
• Encyclopedia of controlled drug delivery systems.

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THANK YOU
Cell No 00919742431000 E-mail
bknanjwade_at_yahoo.co.in