Non-Fickian Profile of In Vitro Drug Release from Liquid Droplet Dispersion-Type Ointments

Abstract

The linear slope obtained from plotting the cumulative amount of drug released against the square root of time (Q-√t plot) has generally been used as an index of in vitro drug release from topical semisolid dosage forms. This parameter is also designated as an index for in vitro drug release in SUPAC-SS. An in vitro drug release test was performed with liquid droplet dispersed ointments consisting of white petrolatum (Vaseline), liquid paraffin, N-methylpyrrolidone (NMP, local phase), and mometasone furoate (MF) as a drug. The linearity of the Q-√t plot was not realized when the NMP concentration was incorporated more than 8%: An initial burst release of MF was observed, depending on the amount of NMP incorporated, followed by a straight line. This is because NMP has relatively high compatibility to the continuous phase of the white petrolatum base by which the effective drug concentration in the continuous phase increases. For practical purposes to verify the equivalence of two formulations, the in vitro release profiles could be simply compared statistically. When the test is used for comparison of the efficacy of formulations, the Q_t (the cumulative amount of drug released for time t) seems to be a suitable index that displays good correlation with in vivo responses.