Applications of a new device (spindle) for improved characterization of drug release (dissolution) of pharmaceutical products.

Abstract

A crescent spindle (patent pending) is described which may be used in place of the USP paddle component in USP dissolution apparatus 2. The new spindle is curve shaped, corresponding to the bottom of a dissolution vessel, with attached bristles to fill in the gap between the spindle and the surface of the vessel. The geometry of the new spindle provides more efficient mixing than the USP paddle and prevents accumulation of disintegrated material (no cone formation). Using the new spindle, in comparison with the USP paddle, dissolution characteristics of three drug products: 250 mg amoxicillin capsules, 15.6 g acetylsalicylic acid (ASA) boluses and 200 mg carbamzepine tablets were evaluated. The experimental conditions for dissolution testing with the two stirring devices included; 900 ml of 0.05 M phosphate buffer, pH 6.8 with 50 rpm, 900 ml of 0.05 M acetate buffer, pH 4.5-ethanol (7:3) with 50 rpm, and water containing 1% sodium lauryl sulphate with 75 rpm for amoxicillin capsules, ASA boluses and carbamazepine tablets, respectively. Uncharacteristic of the test products, which are fast release, the USP paddle provides significantly slower drug release. For example, 90 min for <80% drug release vs. 10 min for >90% for amoxicillin capsules and 6 h for 80% vs. 30 min for >90% for ASA boluses with USP paddle vs. the new spindle. In case of the carbamazepine tablets, three products which are bioequivalent and prescribed interchangeably, the USP paddle method shows significantly different dissolution characteristics. However, with the new device, all these products show similar drug release characteristics, a better reflection of product release characteristics and in vivo drug release behaviour. Compared with the USP paddle, the suggested device (spindle) provides improved stirring and mixing which appears to provide more appropriate (biorelevant) characterization of pharmaceutical products.