Pharmaceutical polymers

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.

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] -

CLASSIFICATIONA. 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.

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.

Criteria Followed In Polymer SelectionIt 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 Dosage FormsTablets : - As binders

- To mask unpleasant taste - For enteric coated tablets

Liquids : - Viscosity enhancers

- For controlling the flowSemisolids :

- In the gel preparation - In ointments

In transdermal Patches

Reservoir Systems - Ocusert System

- Progestasert System- Reservoir Designed Transdermal Patches

Matrix SystemsSwelling Controlled Release SystemsBiodegradable SystemsOsmotically controlled Drug Delivery

GENERAL MECHANISM OF DRUG RELEASE FROM POLYMERThere 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

Drug release from typical matrix release system

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 is transdermal system .

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

ENVIRONMENTALLY RESPONSIVE SYSTEMIt 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.

Drug delivery from (a) reservoir and (b) matrix swelling-controlled release systems.

BIO DEGRADABLE POLYMERBiodegradable 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

Mechanism of BiodegradationA. 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.

DRUG RELEASE MECHANISM FROM BIOERODIBLE POLYMERS The release of drugs from the erodible polymers

occurs basically by three mechanisms,

I. 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.

II. 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.

III. a homogeneously dispersed drug in the biodegradable polymer. The drug is released by erosion, diffusion, or a combination of both.

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

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:-

1. Chemical erosion2. Physical erosion

CHEMICAL EROSION There are three general chemical mechanisms that cause

bioerosion

1. 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

2. 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

3. 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.