Mixtures of betamethasone butyrate propionate ointments and heparinoid oil-based cream: Physical stability evaluation

Betamethasone butyrate propionate ointment (BBP_O) is mainly used for adult patients in dermatology and is often prescribed as a mixture containing a base or moisturizing cream for various reasons. However, in the case of a moisturizing cream, since this formulation is composed of various ingredients, a physical change is expected to occur by mixing it with an ointment. Therefore, in the present study, the physical stability of a mixture of four BBP_O formulations and heparinoid oily cream (HP_OC) was examined. Layer separation was observed in all mixtures following centrifugation. The near-infrared (NIR) measurement showed a peak at 5200 cm⁻¹ on the lower layer side, which strongly suggests the presence of water. The peak at 5200 cm⁻¹ in the middle layer was hardly observed in the mixtures of two BBP_O generic formulations and HP_OC, thus suggesting that the separation was more advanced in those mixtures than in the others. These two mixtures separated into a semisolid layer (upper side) and a liquid layer (lower side) after 3 h of storage at 37 °C. The NIR measurement of each layer revealed that most of the semisolid layer was oil while the liquid layer was water. Furthermore, backscattered light measurements were conducted to monitor the behavior of the mixture's layer separation. An evaluation using model formulations revealed that the layer separation of the mixtures was due to the propylene glycol (PG) and surfactant content of the two generic BBP_O formulations. Thus, these findings suggest that excipients need to be considered in selecting formulations for mixtures of skin preparations.