Release of Lonapalene from Two-Phase Emulsion-Type Ointment Systems

Abstract

The in vitro release of lonapalene, a novel nonsteroidal antipsoriatic agent, was studied from two-phase emulsion-type ointment systems into a perfect sink of propylene carbonate at 32°C. Lonapalene was completely solubilized in the ointments consisting of an internal phase of propylene carbonate (PC)–propylene glycol (PG) mixture dispersed within an external phase of a petrolatum base. The PC:PG ratio was varied to investigate separately the effects of (1) the initial concentration of lonapalene, (2) its saturation level, and (3) the volume fraction of the internal phase. The release profile consisted of an initial release rate which was higher than the ensuing diffusion-controlled release rate. The initial rate was attributed to the release of lonapalene from the surface globules of internal phase directly into the sink. Both rates increased with increasing lonapalene initial concentration in the ointment. For ointment systems in which the saturation level of lonapalene was kept constant, neither release rate was affected by the increasing volume fraction of the internal phase up to 12%. Further increase in this volume fraction to 25% afforded a significantly higher initial rate, while the diffusion-controlled rate was unchanged. However, an increase in the volume fraction of the internal phase with a concomitant decrease in the saturation level of lonapalene in the ointment resulted in a decrease in the initial rates and, to a lesser degree, the diffusion-controlled release rates. The diffusion coefficient in the external phase, calculated from the effective diffusion coefficient, was (2.68 ± 0.24) × 10⁻⁹ cm²/sec.