Formulation And Preparation Research Of Methylprednisolone Aceponate Cream

Methylprednisolone aceponate (MPA) is one of the fourth generation glucocorticoid dr-ugs, primarily for the treatment of psoriasis, eczema and atopic dermatitis. MPA cream was firstly marketed in Germany in 1992, but has not been commercially available in China. In the skin, MPA is hydrolyzed to its active metabolite,6a-methylprednisolone-17-propionate (6-MP-17-P),which shows 3-fold affinity to the receptor, suggesting higher anti-inflammatory efficacy than its parent drug. However,6-MP-17-P will immediately be inactivated by conj-ugation with glucuronic acid in the blood. The purpose of this study was to develop a MPA cream and evaluate its physical stability, skin permeability and skin accumulation, with marketed MPA cream as control.Firstly, the contents of oil phase, surfactants, penetration enhancers and solvent in the MPA cream were screened and optimized. MPA creams based on different formulation were prepared and evaluated in terms of physical stability, skin permeability and skin accumulation. The results showed that the oil phase and surfactant had great impact on the physical stability of MPA cream. The content of cetostearyl alcohol and solvent mostly influenced the skin accumulation of the drug. And penetration enhancers affected the skin permeability of MPA. Therefore, etostearyl alcohol, solvent, surfactant are determined as the major factors effecting the physical stability, skin accumulation and permeability of MPA cream. Formulation optimization of MPA cream was performed by 33 orthogonal experiments. The optimized MPA cream consisted of cetostearyl alcohol ?1, solvent ?2 and penetration enhancers ?2. Finally, the content of other additional agents, like preservative and antioxidant, were determined.The preparing procedure of MPA cream was evaluated in terms of emulsifying equipments, emulsification time, stirring speed and homogenization pressure. The MPA screams prepared at different preparing procedure were assessed with physical stability, uniformity and particle size of drops. The results showed that comparing to MPA screams prepared using ball mill and high pressure homogenizer, MPA scream obtained using high-speed homogenizer exhibited more similar to the advantan cream in uniformity and particle size of the drops. Therefore, high-pressure homogenizer was determined as the suitable equipment for the preparation of MPA cream. Then, prepration procedure parameters, including emulsification time, stirring speed and homogenization pressure, were optimized using 33 orthogonal experments. The results showed that all the three factors have significant impact on the physical stability of MPA cream, and the impact degrees were ranked in the order of emulsification time> homogenization pressure> stirring speed. Based on above results, the optimal preparation procedure was determined as:emulsification time B2,homogenization pressure C1,stirring speed A3.In conclusion, MPA cream developed in our work presents good physical stability and comparable skin permeability and skin accumulation to the marketed MPA cream.