BIO-COMPATIBLE AND BIO -DEGRADABLE POLYMERS

CONTENTS

DRUG RELEASE MECHANISMS THROUGH POLYMER MATRIX

INTRODUCTION

POLYMERS AND ITS APPICATIONS

CONCLUSION

REFERENCES

POLYMERSMacromolecule that is formed by linking of repeating units through covalent bonds in the main backboneProperties are determined by molecular weight, length, backbone structure, side chains, crystallinity Resulting macromolecules have huge molecular weights Terminology: mer: a unit monomer: one unit dimer: two units trimer: three units tetramer: four units polymer: many units oligomer: few units fixed in size

Entrapment or EncapsulationDuring the 1970, scientists first began to encapsulate and entrap drugs within polymers

Encapsulation involves surrounding drug molecules with a solid polymer shell

polymer

Entrapment involves the suspension of drug molecules within a polymer matrix.

gdrugDrugpolymer

Drug Release By Diffusion

Early encapsulation and entrapment systems released the drug from within the polymer via molecular diffusion

When the polymer absorbs water it swells in size

Swelling created voids throughout the interior polymer

Smaller molecule drugs can escape via the voids at a known rate controlled by molecular diffusion (a function of temperature and drug size)

AddwaterAddtime

Drug Release By Erosion

Modern delivery systems employ biodegradable polymersWhen the polymer is exposed to water hydrolysis occursHydrolysis degrades the large polymers into smaller biocompatible compounds

mermermermermermermermermermermermermermermermermermermermermermermermermermerBulk erosion processSurface erosion processPolymerWater attacks bond

Bulk Erosion(e.g. poly lactide, polyglycolic acid)

These small compound diffuse out of the matrix through the voids caused by swelling

Loss of the small compounds accelerates the formation of voids thus the exit of drug moleculesAddwaterAddtime

Surface Erosion(e.g., polyanhydrides)When the polymer is exposed to water hydrolysis occurs

Hydrolysis degrades the large polymers into smaller biocompatible compounds

These small compound diffuse from the interface of the polymerLoss of the small compounds reveals drug trapped within

Note these polymer do not swell.

Addwater

INTRODUCTION

Biocompatible polymer lacks adverse response, immunogenicity histocompatability of the material upon injection.

Biodegradation relates to the breakdown of the polymer into its monomeric units upon coming contact with bodyfluids, enzymes.

Biocompatible and Biodegradable which are used as interchangeable terms to polymers.

The term biocompatible polymers are used to denote all transient polymeric materials, regardless of their chemical type, origin, and mode of clearance or absorption from the application site.

Biocompatible polymers can be derived from 1 Naturally occurring polysaccharides and proteins, 2 Totally synthetic polymers, or 3 Combinations of natural and synthetic components

POLYSACCHARIDES

Acacia, known as gum arabica, is widely used as an emulsifier and a viscosity modifier

Tragacanth is widely used as a natural emulsifier in conjunction with acacia and is an effective viscosity modifier for suspension formulations.

It contains a variety of methoxylated acids that upon contact with water become a gel.

Xanthan gum is an anionic, water-soluble polysaccharide obtained from a pure culture fermentation of Xanthomonas camprestris

It has been used to develop sustained-release dosage forms because the high-molecular-weight gum dissolves slowly in water.

CELLULOSE

Cellulose is a polysaccharide; it is a natural polymer . It consists of glucose repeating units, bridged with oxygen. Each repeating unit has three hydroxyl groups per molecule of glucose.

Its high crystallinity results from the strong hydrogen bonding

Microcrystalline cellulose

Two types of applications of microcrystalline cellulose are dry powders and aqueous dispersions. Microcrystalline cellulose are used for pharmaceutical applications as fillers, binders ,disintegrants, lubricants, and flow aids.Microcrystalline cellulose is a good candidate for fillers because it is chemically inert, free from organic and inorganic contaminants, and compatible with other active drugs and excipients.

Cellulose acetate alone or in combination with cellulose triacetate or cellulose butyrate is used as a semipermeable membrane for osmotic pumping tablets, primarily in controlled release systems.

The permeability of the membrane can be further modulated by adding water-soluble excipients to the cellulose esters.

Water-soluble hydroxypropylmethyl cellulose and water-insoluble cellulose acetate are further treated with phthalic anhydride or succinic anhydride to yield hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, and hydroxypropylmethylcellulose acetate succinate.

These polymers are used as enteric materials and are water soluble or insoluble above or below a specific pH, respectively.

Chitin and chitosan

Chitosan is a useful derivative of chitin, which is the second most plentiful natural polymer.

Chitin is a naturally occurring polysaccharide consisting of amino sugars. It is a natural polymer formed of repeating monomer units of -(1-4)-2-acetamido-2-deoxy-D-glucose.Crustaceans, Insects:exoskeletonMajor source (currently: shellfish waste: animal feed)Chitin ChitosanInsectsShrimp

FungiFungi

Chitosan and its derivatives have been applied to enhance the absorption of proteins (e.g., insulin) and polypeptides (e.g.,buserelin).

N-Trimethyl chitosan chloride exhibits opening of the tight junctions of the intranasal and intestinal epithelial cells so that the transport of hydrophilic compounds is increased through the paracellular transport pathway.

Chitosan and hydroxypropyl chitosan were found to be enzymatically degraded so that they can be used for implantable controlled-release dosage forms. chitosan and chitin have been used in numerous areas such as wound dressing, cholesterol control, food stabilization, hair/skin care, and cell/enzyme immobilization.artificial sskin

Alginates

Alginate is a linear polysaccharide (MW 47,000 to 370,000) extracted from brown seaweed (mainly Laminaria) consisting of D-mannuronic acid and L-guluronic acid residues.

Sodium alginate forms a flexible, translucent gel upon contact with Calcium chloride solution (i.e., cross-linking) by replacing the hydrogen bonding

.The longer the cross-linked gel remains in the calcium chloride solution, the more rigid the gel that will be obtained. The cross-links can be broken by placing them into brine.. Sodium alginates and propylene glycol alginate are used for a variety of applications such as cell immobilization (e.g., encapsulation of pancreas cells), wood dressings, antacids (e.g.,Gaviscon), dental impression materials, pharmaceutical excipients, and drug delivery

GELATIN

There are two types of gelatin, depending on the source material and the preparation 1 Type A is derived from an acid process, primarily of pigskin 2.Type B is derived from alkaline or lime and acid processes, primarily of cattle or calf skins and bones where the collagen is older and densely cross-linkedThe film-forming property of gelatin finds many applications in pharmaceutical products (e.g., hard and soft capsules).Gelatin is amphoteric and amphiphilic and thus has limited emulsifying properties (HLB 9.8) (e.g., whipped cream) that can be used in water-in-oil emulsionsGelatin is also used for tablets, suppositories (e.g., glycerinated), hemostatics

Hydrogels(e.g. polyacrylic acids)

Cross-linked, hydrophilic, 3-D polymer networks that are highly permeable

Do not swell in the presence of water unless activated

Swelling activate by pH, temperature, electric field

Drug release happens via void generated & diffusion (diffusion rate is regulated by cross-linking ratio)

mermermermermermermermerAdd water+activatormermermermermermermermer

Hydrogels have been used extensively for the controlled release of bioactive molecules and the encapsulation of cells.

In particular, the use of hydrogels is increased for tissue engineering for tissue repair or tissue regeneration in the body.

.Hydrogels are biocompatible

Enzyme-mediated HA (hyaluronic acid-tyramine) gel formationin vivo shows promise for achieving effective drug therapy and tissue regeneration.

The new materials are being examined for controlled protein release, immunocancer therapy, and tissue engineering

PolyanhydridesPolyanhydrides were specifically prepared in attempts to produce surface-eroding dosage forms.

A wide variety of aliphatic and aromatic monomers have been used to prepare surface-eroding polyanhydride polymers

Aliphatic polyanhydrides are normally prepared from dicarboxylic acids such as adipic acid, sebacic acid (SA) and fumaric acid (FA).

The release of a number of drugs from polyanhydride matrices has been studied including ciprofloxacin, p-nitroaniline, cortisone acetate, insulin and a variety of proteins

In many instances drug release was reported to coincide with polymer degradation.

Polyanhydrides shows more biocompatability

Poly(esters) Polylactic Acid, Polyglycolic Acid, and Polycaprolactone

Poly(esters) are the best widely used biodegradable and biocompatible materials.

There are a number of different grades of poly(lactic acid) (PLA), poly(glycolic acid) (PGA), and copolymers of lactic and glycolic acids (PLAGA) with respect to molecular weights and compositions.

One of the major advantages of using PLA, PGA, PLAGA, and polycarprolactone (PCL) is that the byproducts of the biodegradation are lactic and glycolic acids, which are chemical compounds naturally found in the human body.

As a result, these polymers are biocompatible, have been used for surgical sutures, and are adapted to pharmaceutical applications (especially, controlled release of proteins and peptides).

Silicone polymers

Silicone polymers are one of the most widely used types of polymer within the medical and pharmaceutical industries.

Silicone polymers are inorganic polymers with no carbon atoms in the backbone chain, which is a chain of alternating silicon and oxygen atoms.

Silicone polymers are highly biocompatible, easily fabricated, and highly permeable to many important drugs.

Besides, they can be sterilized by heat, which is an important aspect for implantable devices. Common silicone polymers are 1. polymethylphenylsiloxane and 2 . polydimethylsiloxane, 3 . polydiphenylsiloxane. .

Most silicone polymers are synthesized by the condensation polymerization of purified chlorosilane and water.

Dimethicones are liquid polymers having the general form

The dimethicones are prepared over a wide range of viscosity grades. The polymers have been used as a lubricant for artificial eyes and joints and as water repellants in lotions and creams.

Polymethylphenylsiloxanes are used as a lubricant for syringes

Glassware coated with silicone polymers is rendered so hydrophobic that water drains easily from such containers.

ConclusionThis is the exciting time for the development of biodegradable and biocompatible drug delivery systems.

The sustained delivery of drugs to the body has, practically speaking,become a reality as numerous products have passed regulatory review and proven to be commercially successful.

New polymers continue to be developed

At the same time, new therapeutic applications are being increasingly recognized.

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