By : Prof. Dr. Basavaraj K. Nanjwade M. Pharm., Ph. D KLE University’s College of Pharmacy BELGAUM – 590010, Karnataka, India Cell No: 00919742431000 E-mail:

By :By :Prof. Dr. Basavaraj K. Nanjwade Prof. Dr. Basavaraj K. Nanjwade M. Pharm., Ph. DM. Pharm., Ph. D

KLE University’s College of PharmacyKLE University’s College of PharmacyBELGAUM – 590010, Karnataka, IndiaBELGAUM – 590010, Karnataka, IndiaCell No: 00919742431000Cell No: 00919742431000E-mail: [email protected]: [email protected]

07/09/201007/09/2010 KLE COP, NipaniKLE COP, Nipani 22

CONTENTSCONTENTS

o IntroductionoClassification of PolymersoApplications in Conventional Dosage

FormsoApplications in Controlled Drug

DeliveryoBiodegradable PolymersoNatural PolymersoReferences


INTRODUCTIONINTRODUCTION

• 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.


What is Polymer?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.


• 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] -


A. Based on origin : a) Natural Polymers :

e.g. Proteins – Collagen, Keratin, Albumin Carbohydrates – starch, cellulose, glycogen. DNA, RNA

b) 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.

CLASSIFICATIONCLASSIFICATION


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.


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.


CHARACTERISTICS OF IDEAL CHARACTERISTICS OF IDEAL POLYMERPOLYMER

• 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.


Criteria Followed In Polymer Criteria Followed In Polymer SelectionSelection

• 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.


Applications in Conventional Applications in Conventional Dosage FormsDosage 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


Applications In Controlled Applications In Controlled Drug DeliveryDrug Delivery

• Reservoir Systems - Ocusert System

- Progestasert System- Reservoir Designed Transdermal Patches

• Matrix Systems• Swelling Controlled Release Systems• Biodegradable Systems• Osmotically controlled Drug Delivery


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.


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.



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.


Transdermal Controlled Drug DeliveryTransdermal Controlled Drug Delivery


B. Osmotically Controlled Drug B. Osmotically Controlled Drug Delivery SystemDelivery 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.


C. Biodegradable SystemC. 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.


D. Matrix SystemsD. 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.


E. Swelling Controlled Release E. Swelling Controlled Release SystemsSystems

• 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.


Because of this, laminate swells and generates Because of this, laminate swells and generates hydrodynamic pressure and induces the hydrodynamic pressure and induces the

delivery of drug formulation through the orifice.delivery of drug formulation through the orifice.

Drug delivery orifice

Shape retaining housing

Collapsible drug container

Swellable polymer

Liquid drug formulation

Annular openings


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.


Classification :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


Mechanism of BiodegradationMechanism 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)


• 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.


• 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


A NEW BIODEGRADABLE A NEW BIODEGRADABLE POLYMER POLYKETALPOLYMER 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 failure2. In any protein based vaccine.


Natural PolymersNatural 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.


• 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.


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.


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


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.


Muco–Adhesive PolymersMuco–Adhesive PolymersThese 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.


REFERENCESREFERENCES

• Novel drug delivery systems – Y.W.Chien – Dekker 50

• Eastern Pharmacist – April, 2001. August, 1998

• Bio–adhesive drug delivery system – Dekker 98

• Encyclopedia of controlled drug delivery systems.


Cell No: 00919742431000E-mail: [email protected]

Documents

By : Prof. Dr. Basavaraj K. Nanjwade M. Pharm., Ph. D KLE University’s College of Pharmacy BELGAUM – 590010, Karnataka, India Cell No: 00919742431000 E-mail: