Fabrication and Evaluation of Various Polymeric Matrices for the Formulation of Once-A-Day Controlled Release Tablets of Some Aryl-Propionic Acid Analogs.

Abstract

The main objectives of this research were to synthesize and evaluated some novel functionalized polymers to fabricate, formulate and evaluate in various polymeric matrices of once a day controlled release tablets of Propionic acid analogs, mainly Ibuprofen, Flurbiprofen and Ketoprofen and preparation and development of nanoparticles drug delivery systems to study their release pattern, rate and the involved mechanism in release process of the drug and to develop and evaluate such sustained release drug formulations which can be used less frequent and with more patient compliance. Three new polymers were synthesized including PGA, PGA- co-caprolactone and PGA-co-pentadecalactone. The polymer backbone consisting of two ester-linked, non-toxic, biological monomers, glycerol and polyvinyl adipate, was prepared using a hydrolytic enzyme. A novel polymeric prodrug was also developed by coupling a model drug, Ibuprofen, to polyester, poly (glycerol-adipate-co-pentadecalactone), via ester linkage. Ibuprofen-loaded nanoparticles were also prepared. The polymers, conjugate and nanoparticles were evaluated and characterized by GPC, NMR, FT-IR, U.V, and DSC. Among the three polymers, the particles of Ibuprofen coupled with poly (glycerol-adipate-co- pentadecalactone) showed a burst release followed thereafter by very slow release into pH 7.4 phosphate buffer. Solubility of the drugs was checked by the use of UV. Spectrophotometer (1601-Shimadzu. Japan) as described by the method of Higuchi and Connors. In this preformulation study, six solvents were used including Phosphate buffers of pH 7.4, 7.2 and 6.8, 0.1 N NaoH, 0.1 N HCl solution and distilled water.