克立硼罗软膏体外释放特性研究

Study on Release of Crisaborole Ointment in vitro

目的建立克立硼罗含量测定方法及软膏体外释放方法,为克立硼罗软膏一致性评价提供参考依据。方法采用HPLC法测定克立硼罗含量,以改良Franz扩散池法研究软膏体外释放特性,以优选的接收介质、人工膜、上药量和转速等条件对市售及自研克立硼罗软膏进行体外释放特性比较。结果接收介质选择pH 7.4磷酸盐-丙三醇(1∶1),人工膜选择0.45μm混合纤维素膜,上药量选择200 mg,转速选择300 r·min^(-1),建立体外释放方法,计算得市售与自研软膏释放速率分别为(167.97±5.86)和(161.20±5.47)μg/(cm^(2)·h^(1/2)),两者释药行为符合Higuchi模型。结论HPLC含量测定方法专属性强,精密度良好,适用于克立硼罗含量测定,市售与自研克立硼罗软膏的释放速率接近,体外释放特性可视为等效。

OBJECTIVE To establish a method for the determination of the content and in vitro release method of crisaborole ointment,and to provide a reference basis for the consistency evaluation of crisaborole ointment.METHODS High performance liquid chromatography(HPLC)was employed to determine the content of crisaborole,modified Franz diffusion cell method was applied to perform in vitro release experiments,and the in vitro release characteristics of the commercially available and self-developed crisaborole ointment were compared adopting the preferred receiving medium and artificial membrane.RESULTS The receiving medium was selected as pH 7.4 phosphate-glycerol(1∶1),the artificial membrane was selected as 0.45μm mixed cellulose membrane,the loading volume was selected as 200 mg,and the speed was selected as 300 r·min^(-1) to establish the in vitro release method.The release rates were calculated to be(167.97±5.86)and(161.20±5.47)μg/(cm^(2)·h^(1/2))for commercially available and self-developed crisaborole ointments,respectively.The release behaviors of both were in accordance with the Higuchi model.CONCLUSION The HPLC method was applicable for the content determination.The release rates of the two were close and could be regarded as equivalent.