Preformulation studies a view to develop fast release solid dosage form

Abstract

The purpose of the present investigation was to increase the solubility and dissolution rate of rofecoxib by the preparation of its solid dispersion using Polyethylene glycol 6000 as a hydrophilic carrier in different proportion ranging from 1:2 to 1:12 using solvent evaporation method. Drug polymer interactions were investigated using Fourier transform infrared spectroscopy (FTIR). The solid dispersions prepared were subjected to assay, solubility and in vitro dissolution studies. The obtained results showed that the solubility was increased 5 fold over that of pure rofecoxib with 1:10 ratio of carrier and the dissolution rate considerably enhanced. The drug-to-carrier ratio was the controlling factor for dissolution improvement with maximum dissolution observed with 1:10 solid dispersion. This increase in the dissolution rate was due to improved wettability by the carrier. At higher level (after 1:10 ratio), the negative effect on dissolution appears that may be due to distortion of molecular dispersion structure, which leaves an insoluble drug particle and increased accumulation of carrier molecule in the bulk, to cause a saturation, by which further solubility of rofecoxib is retarded. FTIR spectra revealed no chemical incompatibility between the drug and PEG6000. The optimized 1:10 (RXB: PEG6000) solid dispersion was used in the formulation of tablet using microcrystalline cellulose as superdisintegant by direct compression. The Flowability and compressibility of the blend was found to be fair for compression. The tablet weight was maintained at nearly 180mg. Keywords: Rofecoxib; Polyethylene glycol 6000; solid dispersions; FTIR; solvent method