Preparation and in vitro evaluation of Allopurinol-Gelucire 50/13 solid dispersions.

Abstract

The rate-limiting step to absorption of drugs from the gastrointestinal tract is often dissolution from the dosage form. Allopurinol is a commonly used drug in the treatment of chronic gout or hyperuricaemia associated with leukaemia, radiotherapy, anti-neoplastic agents. One of the major problems with allopurinol is that, it is practically insoluble in water, which results in poor bioavailability after oral administration. In the present study, solid dispersions of allopurinol were prepared by solvent evaporation method, kneading method, co-precipitation method, co-grinding method and closed melting method to increase its water solubility. In the present study amphiphilic carrier like gelucire 50/13 was used in the ratio of 1:1, 1:2 and 1:4. Prepared solid dispersions were characterized in the liquid state by phase solubility studies and in the solid state by Differential Scanning calorimetric analysis, Powder X-ray diffractometry and Fourier Transform Infrared spectroscopy. The aqueous solubility of allopurinol was preferential by the presence polymer with increasing concentration. Solid state characterizations indicated that allopurinol was present as an amorphous material and entrapped in polymer matrix.Mathematical modeling of in vitro dissolution data indicated the best fitting with Korsemeyer-Peppas model and the drug release kinetics primarily as Non-Fickian diffusion. Therefore, the current study showed that gelucire 50/13 has a significant solubilizing effect on allopurinol. Keywords: Allopurinol, gelucire 50/13, closed melting-method, co-grinding, dissolution study, powder X-ray diffraction analysis