Once a Day Pellets of Theophylline by Extrusion Spheronization Technique Using Gelucire® Matrix

Abstract

Theophylline, a xanthine bronchodilator has narrow therapeutic index (5 – 15 µg/mL). The aim of the present work was to prepare once a day pellets of theophylline containing at least 75% of the drug by extrusion spheronisation technique. Theophylline has good aqueous solubility of about 10 mg/mL in purified water at 37 ºC. Various grades of Gelucire^® were used as release retardant. The developed formulations met the in vitro release profile as per USP 30 specifications. Interestingly addition of oil helped in retarding initial burst as well as in stabilising Gelucire^® matrix from the aging effects which was confirmed by varying the concentration of the oil. The stabilisation of the formulation against aging was confirmed by DSC and in vitro release studies of the fresh and the aged samples. The developed pellets were evaluated for size, spherecity, drug content, flow rate, bulk density, tap density and in vitro release studies as per USP 30. The optimum formulation was with Gelucire^® 43/01 and Avicel^® CL611.