过氧苯甲酰凝胶体外释放研究

In vitro release study of benzoyl peroxide gel

摘要

目的: 采用扩散池法对过氧苯甲酰凝胶的体外释放度进行研究,测定释放曲线并对释放数据进行模型拟合。方法: 采用Franz扩散池,以PEG400-无水乙醇-水(25∶25∶50)为释放介质,以孔径0.45 μm的尼龙膜为人工膜,采用高效液相色谱法(HPLC)测定释放量,采用零级模型、一级模型、Korsmeyer-Peppas模型和Higuchi模型拟合释放曲线,确定最优释放模型。结果: 建立了过氧苯甲酰凝胶的体外释放测定方法,过氧苯甲酰零级模型拟合最优,苯甲酸Higuchi模型拟合最优。结论: 本研究建立的体外释放方法可用于过氧苯甲酰凝胶的释放度测定,并为类似难溶性药物制剂的质量研究提供参考。

Abstract

Objective: To investigate the in vitro release behavior of benzoyl peroxide gel using a diffusion cell method, and to obtain release profiles with subsequent kinetic model fitting. Methods: The method was established with Franz diffusion cell. The PEG400-ethanol-water (25∶25∶50) is selected as receiving medium. The nylon membrane with 0.45 μm is used as the artificial membrane. The release amount was determined by high performance liquid chromatography (HPLC). The release data were fitted to zero-order, first-order, Korsmeyer-Peppas, and Higuchi models to identify the optimal release model. Results: An in vitro release testing method for benzoyl peroxide gel was successfully established. The release data of benzoyl peroxide were best fitted by the zero-order kinetic model, whereas the release data of benzoic acid were best described by the Higuchi model. Conclusion: The established in vitro release method is suitable for evaluating the release characteristics of benzoyl peroxide gel and provides a useful reference for the quality assessment of topical formulations containing poorly soluble drugs.

关键词

过氧苯甲酰凝胶 / 体外释放试验 / 一致性评价 / 扩散池 / 高效液相色谱法

Key words

benzoyl peroxide gel / in vitro release test / consistency evaluation / diffusion cell / HPLC

[1] EICHENFIELD DZ, SPRAGUE J, EICHENFIELD LF. Management of acne vulgaris: a review[J]. JAMA, 2021, 326(20): 2055-2067.
[2] 中华医学会, 中华医学会杂志社, 中华医学会全科医学分会, 等. 寻常痤疮基层诊疗指南(2023年)[J]. 中华全科医师杂志, 2023, 22(2): 140-141.
[3] XU XM, AL-GHABEISH M, RAHMAN Z, et al. Formulation and process factors influencing product quality and in vitro performance of ophthalmic ointments[J]. Int J Pharm, 2015, 493(1-2): 412-425.
[4] BAO QY, JOG R, SHEN J, et al. Physicochemical attributes and dissolution testing of ophthalmic ointments[J]. Int J Pharm, 2017, 523(1): 310-319.
[5] 国家药品监督管理局药品审评中心. 皮肤外用化学仿制药研究技术指导原则(试行)[EB/OL].(2021-03-15)[2024-12-01].https://www.cde.org.cn.
[6] 国家药品监督管理局药品审评中心. 局部起效化学仿制药体外释放(IVRT)与体外透皮(IVPT)研究技术指导原则(试行)[EB/OL].(2025-01-10)[2024-12-01].https://www.cde.org.cn.
[7] SUHAIL M, WU PC, MINHAS MU. Using carbomer-based hydrogels for control the release rate of diclofenac sodium: preparation and in vitro evaluation[J]. Pharmaceuticals (Basel), 2020, 13(11): 399.
[8] 张海龙, 严全鸿, 朱海健, 等. 多变量置信区间法和模型依赖法在溶出曲线相似性比较中的应用[J]. 药学进展, 2016, 40(12): 916-923.
[9] SIEPMANN J, PEPPAS NA. Higuchi equation: derivation, applications, use and misuse[J]. Int J Pharm, 2011, 418(1): 6-12.
[10] 高海素, 陈网桦, 陈利平, 等. BPO在等温条件下的热稳定性研究[J]. 安全与环境学报, 2014, 14(1): 109-112.
[11] LIU SH, HOU HY, SHU CM. Thermal hazard evaluation of the autocatalytic reaction of benzoyl peroxide using DSC and TAM III[J]. Thermochim Acta, 2015, 605: 68-76.