Chellquist E M, Gorman W G
Sterling Winthrop Pharmaceuticals Research Division, Rensselaer, New York 12144.
Pharm Res. 1992 Oct;9(10):1341-6. doi: 10.1023/a:1015873805080.
Saturated solubility and reaction rate constants for the decomposition of benzoyl peroxide in solution and suspension were determined for use in formulation development. The solvents studied included ethanol, propylene glycol, and cosolvent mixtures of PEG 400 and water. The solubility of benzoyl peroxide was inversely related to the solvent polarity, with greater solubility occurring with semipolar solvents. The stability of benzoyl peroxide in solution was dependent on the solvent, concentration of benzoyl peroxide, and temperature. The compound was least stable in PEG 400. Stability was improved when water was added to PEG 400. Similar solvent effects were observed in suspension. In benzoyl peroxide suspensions of PEG 400 and PEG 400/water blends, benzoyl peroxide stability was dependent on solubility, with improved stability occurring in blends where the benzoyl peroxide was least soluble. Thus, solution formulations of benzoyl peroxide in pharmaceutically acceptable solvents are unlikely to show good stability; however, suspension formulations should be reasonably stable if the vehicle is selected to provide low benzoyl peroxide solubility.
测定了过氧化苯甲酰在溶液和悬浮液中的饱和溶解度及分解反应速率常数，以用于制剂研发。所研究的溶剂包括乙醇、丙二醇以及聚乙二醇400与水的混合溶剂。过氧化苯甲酰的溶解度与溶剂极性呈负相关，半极性溶剂中的溶解度更大。过氧化苯甲酰在溶液中的稳定性取决于溶剂、过氧化苯甲酰的浓度和温度。该化合物在聚乙二醇400中最不稳定。向聚乙二醇400中加水可提高稳定性。在悬浮液中也观察到了类似的溶剂效应。在聚乙二醇400和聚乙二醇400/水混合物的过氧化苯甲酰悬浮液中，过氧化苯甲酰的稳定性取决于溶解度，在过氧化苯甲酰溶解度最低的混合物中稳定性提高。因此，过氧化苯甲酰在药学可接受溶剂中的溶液制剂不太可能具有良好的稳定性；然而，如果选择能使过氧化苯甲酰溶解度低的载体，悬浮制剂应该相当稳定。
