Effects of Long-Chain Alcohols on Conversion of Prednisolone Crystal in Oil in Water Type Ointments

The influence of ointment composition and storage temperature on the conversion of the prednisolone anhydrous form (A-PD) to its hydrated form (C-PD) in O/W type ointment was studied using an X-ray diffractmeter and a polarizing microscope. When either stearyl alcohol or cetyl alcohol alone was added to the ointment, A-PD was easily converted into C-PD, especially at low storage temperature. On the other hand, when a mixture of alcohols was used in a proper ratio, the conversion of A-PD to C-PD was retarded. Particularly, when stearyl alcohol and cetyl alcohol were mixed in the ratio of approximately 2 : 3, A-PD remained most stable. When O/W type ointment, including A-PD, was stored at high temperature (37°) for a long time and then moved to a low temperature (5°) for storage, it was not easy to convert into C-PD. These results were due to the property of three polymorphisms (α, β, and γ) of long-chain alcohols. The ointment structure containing the α-form was stable enough to stabilize A-PD, while that containing the β- or γ-form was less stable.