Evaluation of the Pharmaceutical Properties of Clobetasol Propionate Ointments and Base Stability of the Mixture with Heparinoid Oil Based Creams

Abstract

Clobetasol propionate ointment (CLPO) formulations have been classified as members of the "strongest" steroidal efficacy group, with eight of these formulations currently marketed in Japan. Evaluations of pharmaceutical properties of each formulation revealed three classification types: droplet dispersion type containing propylene glycol (PG) and surfactant, type with surfactant but not PG, and other types. These rheological properties were diverse, with no correlation found between viscosity and ointment type. However, when CLPO and six types of heparinoid oil-based cream (HPOC) formulation mixtures were stored at 37℃, a liquid layer was observed starting at 24 h for one CLPO formulation in which polyoxyethylene hydrogenated castor oil 40 was used as a surfactant out of the four droplet-dispersion type ointments and two low-viscosity HPOC formulations. In contrast, one other type of CLPO formulation that contained a surfactant with polysorbate 80, but not PG, exhibited a liquid layer for all of HPOC formulations. This suggests that CLPO formulations that contain a surfactant with a high hydrophilic-lipophilic balance value are likely to generate a liquid layer for mixtures containing HPOC formulation. The present results demonstrate that not only the pharmaceutical properties of the eight CLPO formulations differ from one another, but also that the stabilities of HPOC formulation mixtures are significantly different. Therefore, pharmacists need to focus on inactive as well as active pharmaceutical ingredients to select formulations that patients will want to use, in addition to successfully treating their pathological conditions.