DEVELOPMENT AND VALIDATION OF AN IN-VITRO DISSOLUTION METHOD FOR A FLOATING DOSAGE FORM WITH BIPHASIC RELEASE CHARACTERISTICS

The present study describes the development of a dissolution method fo r a floating dosage form using HALO(TM)-propranolol capsules containin g propranolol base dissolved in oleic acid. A modified paddle dissolut ion method in which the paddle blades were set to the surface of the d issolution medium was shown to be effective for assessing HALO(TM)-pro pranolol capsules, characterised by having both rapid release and sust ained release properties. The standard paddle or-basket methods descri bed 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 re lease component of the formulation. Further studies showed that the mo dified paddle method resulted in reproducible biphasic-release dissolu tion 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 perf ormance was adversely affected by temperatures below 36.8 degrees C bu t unaffected up to a temperature of 37.5 degrees C. Increasing the bil e acid concentration in the dissolution medium from 7 to 14 mM did not alter the dissolution profile. The physiological implications of thes e results are discussed.