Box-Behnken法优化阿奇霉素滴眼液处方及制备工艺的考察

目的:含透明质酸钠(SH)的阿奇霉素(AZI)滴眼液最优处方的筛选及制备工艺的考察。方法:采用Box-Behnken设计,以滴眼液p H、透明质酸钠的相对分子质量和透明质酸钠的质量浓度为因素,以药物在泪液中的动力学行为作为评价指标,考察各因素的影响,确定最合理的处方。进一步制备了阿奇霉素滴眼液,根据《中国药典》要求考察滴眼液的渗透压,黏度及表面张力。结果:阿奇霉素滴眼液的最优处方为溶液p H 5.5,透明质酸钠相对分子质量150万,透明质酸钠质量浓度为0.6 g·(100 m L)-1。为保证滴眼液的无菌要求,制剂不耐受高压蒸汽灭菌,需无菌操作。结论:采用Box-Behnken设计筛选处方是可行的,依据最优处方制备的阿奇霉素滴眼液能有效延长药物结膜滞留时间,同时满足药典对滴眼液渗透压及黏度的要求。

Formulation optimization and preparation process investigation of azithromycin eye drops

OBJECTIVE To optimize the formulation of azithromycin (AZI) eye drops containing sodium hyaluronate (SH) and investigate the preparation process. METHODS Three main significant factors, the pH of the eye drops, the molecular weight of SH and the mass concentration of SH, were taken into consideration, and Box-Behnken design was used with pharmacokinetics parameters as the indexes to determine the optimum formulation. Then, the azithromycin eye drops were further prepared and the osmotic pressure, viscosity and surface tension of the eye drops were examined according to the requirements of Ch.P 2015. RESULTS The optimum formulation of azithromycin eye drops:pH 5.5, molecular weight of SH 1.5 million, and the mass concentration of SH 0.6 g·(100 mL)^-1. In order to ensure the aseptic requirements of eye drops, the preparation was not tolerated by high pressure steam sterilization, which meant that the preparation process should be conducted under sterile environment. CONCLUSION It is feasible to optimize the formulation by using Box-Behnken design. Moreover, azithromycin eye drops made from the optimum formulation can prolong the residence time of drug in eyes, and meet the requirements of ophthalmic osmotic pressure and viscosity in pharmacopoeia.