Application Of Polymer In Controlled Release Formulation

Polymers are becoming increasingly important in the field of drug delivery. The pharmaceutical applications of polymers range from their use as binders in tablets to viscosity and flow controlling agents in liquids, suspensions and emulsions. Polymers can be used as film coatings to disguise the unpleasant taste of a drug, to enhance drug stability and to modify drug release characteristics.
As a consequence, increasing attention has been focused on methods of giving drugs continually for a prolonged time periods and in a controlled fashion.
This technology now spans many fields and includes pharmaceutical, food and agricultural applications, pesticides, cosmetics, and household products.

1. M.Pharm 2 nd Semester Seminar Subject : Advanced Physical Pharmacy Topic : Application Of Polymer In Controlled Release Formulation By: Anindya Jana M.Pharm 1 st Year (Pharmaceutics) Regd. No. : 1661611006

2. Polymer The word “polymer” means “many parts.” A polymer is a large molecule made up of many small repeating units. Polymers are considered to be a subset of macromolecules. Macromolecule refers to any large molecule. A monomer is a small molecule that combines with other molecules of the same or different types to form a polymer.

3. Controlled Drug Delivery System (CDDS) Controlled release  is a term referring to the delivery of compounds in response to time. Controlled release systems have been developed to protect drug from physiological degradation or elimination, to improve patient compliance, and to enhance quality control in manufacturing of drug products.

4. Classification Of Polymers Natural Polymer Protien-based polymer: Collagen, Albumin, Gelatin 2. Polysaccharides: Alginate, Cyclodextrin, Chitosan, Dextran, Agarose, Hyaluronic acid, Starch, Cellulose Synthetic Polymers Biodegradable Polymer a) Polyester: Poly lactic acid, Poly glycolic acid Poly hydroxyl butyrate, Polyester, Polycaprolactone Poly lactide-co-glycolide (PLGA), Poly diaxonone b) Polyanhydride: Poly adepic acid, Poly sebacic acid Poly terpthalic acid c) Polyamides: Poly amino acid, Poly imino carbonate

5. d) Phosphorous based polymer: Polyphosphates, Poly phosphonates, Poly Phosphazenes e) Others: Poly cyanoacrylates, Poly urethanes, Poly ortho ester, Polyacetals etc. Non-Biodegradable polymers a) Cellulose derivative: Carboxy methyl cellulose, Ethyl cellulose Cellulose acetate hydroxyl propyl methyl cellulose b) Silicons: Polydimethyl siloxane, Colloidal silica, Polymethacrylate, Polymethyl methacrylate c) Others: Poly vinyl pyrolidine, Ethyl vinyl acetate, Poloxamine etc.

6. Release Of Therapeutic Agents From Controlled Release System Matrix System In matrix designed drug delivery systems, the drug is homogeneously dispersed, either at the molecular scale or as solid particles, within a polymeric medium. Example Mixing of a polymer with the drug particles followed by direct compression into tablets. (b) Dissolving the drug and polymer in an appropriate solvent followed by solvent removal. (c) By hydrogel swelling within a drug solution. (d) Curing a polymer in the presence of dissolved / dispersed drug. 2. Reservoir Systems In these systems the drug-containing core is separated from the biological fluids by a water insoluble polymeric coat or layer, depending on the geometry of the drug delivery system.

7. Applications of Polymers for Controlled Drug Delivery The Ocusert System The delivery of therapeutic agents to the eye for the treatment of disorders of the eye, (e.g., glaucoma), using conventional drug delivery systems, e.g., drops, ointments, is an inefficient process. The efficiency of ocular drug delivery is improved through the use of polymeric implants that are implanted under the lower cul-de-sac of the eye. In this system pilocarpine is dispersed within an alginic acid matrix which is sandwiched between two layers each composed of poly(ethy1ene-co-vinyl acetate). It is designed to release either 20 µg/h or 40 µg/h of a therapeutic agent for a seven day period following implantation.

8. 2. Transdermal Patches Transdermal drug delivery involves the diffusion of the drug through the skin and ultimately absorption into the systemic circulation. The drug delivery system is composed of several layers, namely a metallic backing layer, which is impermeable to drug diffusion thereby preventing drug loss, the drug containing reservoir, a rate controlling membrane and an adhesive layer. In the matrix drug is dissolved or dispersed with solid polymer (acrylate co-polymer).

9. Literature Articles 1. Choi W. Y. et al. has developed a matrix-type, controlled-release tablet formulation of pelubiprofen (PLB), a recently developed non-steroidal anti-inflammatory drug. He used polymeric excipients including hypromellose , hydroxypropylcellulose , Eudragit ® RS PO, and Kollidon®SR .

10. A formulation containing 12.4% w/w Kollidon SR (K2 tablet) was found the most promising and stable for 6 months in an accelerated stability test. PLB release from K2 tablet was limited at pH 1.2, but gradually increased at pH 6.8 with a surface-erosion.

11. 2. Andersson H et. al. has done the investigation the effect of the molecular weight of HPC on the microstructure and mass transport in phase-separated freestanding Hydroxypropyl cellulose (HPC) / ethyl cellulose (EC) films with 30% w/w HPC. Four different HPC grades were used, with weight averaged molecular weights (Mw) of 30.0 (SSL), 55.0 (SL), 83.5 (L) and 365 (M) kg/mol. Size Exclusion Chromatography with multi-angle light scattering and refractive index detection (SEC-MALS/RI) has used to determine z-average molar mass ( Mz ), weight average molar mass (Mw) and number average molar mass ( Mn ) . The permeability has considered an effective diffusion coefficient in the film. The water permeabilities of the films were determined from radioactive tracer diffusion across the films in the diffusion cell, assuming direct proportionality between the radioactivity and diffused mass.

12. The film with the lowest Mw HPC (SSL) had unconnected oval-shaped HPC-rich domains, leaked almost no HPC and had the lowest water permeability. The remaining higher Mw films had connected complex-shaped pores, which resulted in higher permeabilities . The highest Mw film (M) had the smallest pores and very slow HPC leakage, which led to a slow increase in permeability. Films with grade L and SL released most of their HPC, yet the permeability of the L film was three times higher due to greater pore connectivity. It was concluded that the phase-separated microstructure, the level of pore percolation and the leakage rate of HPC will be affected by the choice of HPC Mw grade used in the film and this will in turn have strong impact on the film permeability.

13. References : 1. D Jones; Pharmaceutical Application For Drug Delivery; Rapra Review Reports; Volume 15; Number 6; 2004. Page 18 -25 2. Chauhan P S N et al.; Pharmaceutical Polymer; Encyclopedia of Biomedical Polymers and Polymeric Biomaterials; 2016; Page 5931 3. Gavasane A et al.; Synthetic Biodegradable Polymers Used in Controlled Drug Delivery System; Clinical Pharmacology & Biopharmaceutics; 2014; Page 1-2 4. Bhoumik D et al.; Controlled Release Drug Delivery Systems; The Pharma Innovation; Volume 1; Number 10; 2012; Page 30-31 5. Choi W Y at el.; Formulation of controlled-release pelubiprofen tablet using Kollidon1 SR; International Journal of Pharmaceutics; Elsevier; 2016; P 564-875 6. Andersson H at el .; The influence of the molecular weight of the water-soluble polymer on phase-separated films for controlled release; International Journal of Pharmaceutics; Elsevier; 2016; Page 223-235

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