PRESENTED BY: A.DASARATHA RAMI REDDY Dept.Pharmaceutics K.L.E.

COLLEGE OF PHARMACY BELGAUM

DEFINITION INTRODUCTION POLYMER CHARACTERISTICS POLYMER PROPERTIES CLASSIFICATION OF POLYMERS BIO DEGRADABLE POLYMERS APPLICATIONS OF POLYMERS IN CONTROL DRUG DELIVERY SYSTEMS

DEFINITION
A Polymer is a substance composed of molecules with

a large molecular mass of repeating structural units or monomers connected by covalent chemical bonds.

INTRODUCTION
Polymer have for decades performed a valuble function

as excipient in tablet and capsule formulations, parental formulation polymers are time enhances. Polymers are capable of offering advanced sophisticated functions to medicine. Polymers are used as carriers for the delivery of drugs, proteins, and targeting moieties.

 The monomers can be linked together to generate liner polymers, branched polymers or cross linked polymers. Linear and branched polymers are referred to as thermoplastic material. Cross linked ploymers are also known as thermosetting materials.

Polymer must be minimal tissue response after injection or

implantation in to the body Polymer must be free of potentially toxic impurities for example residual initiators, catalysts. Polymers are able to prolong drug availability if medicines are formulated as hydrogels or microparticles. Transport a drug to its usually in accessible site of action if formulated as gene medicines.

POLYMER PROPERTIES
Molecular weight and molecular weight distribution

polymer molecular weights can be defined in different ways. 1. The number average molecular weight (Mn) 2. The weight average molecular weight (Mw) 3. The viscosity average molecular weight (Mv) Mw/Mn = poly dispersibility index

Number average molecular weight

Weight average molecular weight

Viscosity average molecular weight

Tensile strength

Mn X 10-5 Polt of tensile strength against number ave mol.Wt for polystyrene

The above graph shows the increase of tensile strength of polystyrene with increase number average molecular weight Polymer with Mn = 40000 has essentially no tensile strength the molecular weight increase tensile strength rapidly increases and ultimately levels of at Mn = 150000

According to the nature of polymer water interactions, polymers are classified as I.Hydrophobic polymers II.Hydrophillic polymers III.Water soluble polymers IV.Hydrogels

 Hydrophobic polymers are essentially water impermeable and, when placed in an aqueous environment will absorb very little water. The amount of water should be absorbed less than 5 wt % Hydrophilic polymers that absorb more than 5 wt %. E.g. copolymerization of hydroxyethyl methacrylate and methyl methacrylate Water soluble polymers E.g. polyvinyl alcohol polycyclic, acid, polyacryl amine and polyethylene oxide Hydro gels are highly hydrophilic or water soluble polymers that have been crossed linked by means of covalent bond.

As the temperature raised polymers under go a transition known as the glass transition temperature Tg. At low enough temperature all amorphous polymers exist in a glassy state. The glass transition temperature of a random copolymer can be estimated by the following relationship.
1 W1 W 2 Tg Tg1 Tg 2

W1 and W2 are the weight fractions of homo polymer Tg1 and Tg2 are glass transitions.

CRYSTALLINITY
Crystalline regions act as crosslink for the Regions this reason stiffen and toughen the polymer and reduce swelling in the solvent. Furthermore, because crystalline regions are also essentially impermeable to water. An enhancement of crystalline results in a decrease in polymer permeability. So the rate of polymer hydrolysis in crystalline regions is significantly reduced.

CLASSIFICATION OF POLYMERS
BIODEGRADABLE POLYMERS Non biodegradable polymer

E.g. Acrolein Glycidly methocrylate Epoxy polymers

Natural polymers a)Protein (Albumin, Collagen, Gelatin) b) Polysaccharides E.g. cellulose, dextrin, Insulin, Hyaluronic acid

Synthetic polymers a) Aliphatic poly (ester) poly (glycolic acid) copolymer b) poly (phosphoesters) c) Poly anhydride d) Poly phosphazene

These polymers comprised of monomers linked to one another through functional groups and have unstable linkages in the backbone They are biologically degraded or eroded by enzymes introduced in vivo or surrounding living cells or non enzymatic process in to oligomers. The drug with poor solubiluty in the polymer E.g. protein and high molecular weight (>500) are not eligible candidates for delivery systems. The bio degradable polymer generally be hydrolytically unstable

 Characters of bio degradable polymers Absence of toxic endogenous impurities or residual chemicals used in their preparation E.g. cross linking agents. Achieve controlled heterogeneous erosion with out any additive Ability to with stand sterilization procedures Degradation products that are excreted readily. The drug release from the bio degradable polymer is generally controlled by 3 competing mechanisms. Diffusion, Swelling, and Erosion.

Degradation is primarily the process of chain cleavage

leading to a reduction in molecular weight Polymer degradation can occur In 2 phases Phase 1 Phase 2 Erosion is defined as the physical degradation of polymer or wax matrix as a result material lost from the polymer generally in the physical state erosion is either surface erosion or bulk erosion

The natural polymers can be proteins and polysaccharides in chemical origin. The modified natural polymers are natural polymers altered to improve the bio degradation profile. The modification of natural polymer is achieved by chemical modification by enzymatic alteration. E.g. chemical modification is the cross linking of gelatin using formaldehyde.

Various natural polymers COLLAGEN : The primary function of collagen is to check tissue Deformation and avoid mechanical failure. ADVANTAGES OF COLLAGEN Low mechanical strength and elasticity in vivo. Variability in drug release kinetics. Bio compatible and nontoxic profile. ALBUMIN : Albumin is employed to design particulate drug release system. Albumin micro spheres have been include insulin,1norgesterol, sulphadiazine, predni solone, 5-FU

Chitin and chitosan: Chitin is a linear polycationic polymer of N-acetylD-glucosamine (N-acetyl-2- amino -2-deoxy-Dglucopyranose) Gastric mucosal injury associated with diclofenac sodium can also be reduced with chitosan. oral mucoadhesive tablets based on chitosan has show immense application potential. Chitosan has gel forming ability at low PH thus it is suitable for oral sustained release system.

Mucoadhesive chitosan coated liposome's could improve oral absorption of insulin. ALGINATE: Alginates can be easily fabricated into particulate carriers they are particualrly benificial as carriers of peptides and sensitive drug moities. Alginate micro spheres have been effectively used for oral delivery of vaccines. They by pass the stomach and there by delivery the antigen to GALT

The application of drug carries plat forms can significantly improve the biodistribution while the addition of a targeted ligand can enhance the selective uptake of the drugs to target tissues.

Polymer at specific cell targeting

Polymer microspheres of poly L-Lactic acid and poly glycolic acid to delivery substance directly to the retinal pigment epithelial cells. After sub retinal delivery the microspheres were degraded in the cytoplasm of the RPE but the fragments were observed for up to 4 weeks. The microspheres were encapsulated with a fluoresent dye that was used as drug marker.

POLYMER IN THE TREATMENT OF CANCER

The 2 thermally responsive polymers that are polyene isopropyl acrylamide co-acrylamide and an artificial elastin-like polypeptide. Mucoadhesive anticancer drug delivery system using 70% deacetylated chitin and cisplatin and 5-FU. The CDDP loaded system showed sustained release of the drug while the 5-FU loaded system exhibited on initial bursting of the agent. The CDDP conjugated to a polyethylene oxide block polylysine co-polymer tracking system has been proven to be effective in the successful treatment of lymph node metastases.

POLYMERS IN BRAIN TARGETING

Nanoparticulate polymeric systems have been widely studied for the delivery of drugs to a specific target site. The major problem in accessing the CNS is linked to presence of BBB. Polymeric NP have bee shown to be promising carriers of CNS drug delivery due to their potential both in encapsulating drugs.

POLYMERS AND DRUG ELUTING STENTS

Application

of polymer include sustained intracoronary delivery of paclitaxes from a polymercoated stent. 3successive layers of drug mixed with biodegradable polymer solutions were applied on SS 316 stents using the air suspension spray coating technique. Polymer coated stents can serve as a reservoir for local drug delivery. Poly L-lactide- cocaprolactone, and PVP Poly L- lactide, poly DL-lactide co glycolide. used for the preparation of paclitaxel drug loaded matrix.

POLYMERS IN ORAL TARGETED DRUG DELIVERY

A floating drug delivery system of drugs (E.g. piroxicam) in the form of microspheres was prepared using an enteric polymer (E.g. ethyl cellulose) and emulsification solvent- evaporation methods. A multiparticulate system of chitosan hydrogel beads exploiting the PH sensitive property and specific bio degradability for colon targeting delivery has been developed for satranidazole.

SMART POLYMERS IN DRUG DELIVERY

Smart polymers are also known as intelligent polymers

sensitive polymers. Application of smart polymers to cancer chemotherapy was proposed by introducing a new PH sensitive functional group responding to change in PH around the physiological condition PH dependent solubility PH dependent swelling PH dependent degradation

Erodible materials commonly empolyed to achieve dissolution CDDS include ethyl cellulose, poly methacrylate with PH indipendent solubility and waxes glyceryl mono sterate and hydrophilic materials like sodium CMC ethyl cellulose and poly methacrylate are commonly used for non swelling reservoir system. HPMC Polymers are used for swellable reservior systems. Ethelene vinyl acetate copolymer used for delivery of pilocarpine in occular drug delivery systems and in progesteron releasing IUD.

REFERENCES
Controlled drug delivery fundamentals and applications.

Edited by: Joseph R.Robinson Vincent H.Lee. Asian journal of pharmaceutics published by med know publications. Vol.3 issued July sept 2009. Controlled drug delivery concepts and advances. By S.P.Vyas, Roop. K.khar Polymers in CDD edited by: Lisbethillum, Stanley.S.davis. Bio pharmaceutics and pharmacokinetics by: D.M.Bharmankar, Sunil.B. Jaiswal

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