Development and validation of an in vitro dissolution method for a floating dosage form with biphasic release characteristics

Abstract

The present study describes the development of a dissolution method for a floating dosage form using HALO TM-propranolol capsules containing propranolol base dissolved in oleic acid. A modified paddle dissolution method in which the paddle blades were set to the surface of the dissolution medium was shown to be effective for assessing HALO TM-propranolol capsules, characterised by having both rapid release and sustained release properties. The standard paddle or basket methods described in the British Pharmacopoeia (1993) were unable to provide either sufficient mixing of the dissolution medium to disperse the oily rapid release material or sufficient mechanical erosion of the sustained release component of the formulation. Further studies showed that the modified paddle method resulted in reproducible biphasic-release dissolution profiles when paddle speeds were increased from 70 to 100 rpm and the dissolution medium pH varied from pH 6.0 to 8.0. Dissolution performance was adversely affected by temperatures below 36.8° C but unaffected up to a temperature of 37.5° C. Increasing the bile acid concentration in the dissolution medium from 7 to 14 mM did not alter the dissolution profile. The physiological implications of these results are discussed.