川芎嗪眼部植入剂的制备及体内外释药相关性研究

Study on preparation of ligustrazine ocular implant and correlation between in vivo and in vitro drug release

目的:制备川芎嗪(TMPZ)眼部缓释植入剂,考察其体外释放、兔眼玻璃体内药动学行为及体内外相关性。方法:使用微量锥形双螺杆混合机,采用热熔融挤出法,以聚乳酸-羟基乙酸共聚物(PLGA)为基质材料制备川芎嗪眼部植入剂,HPLC测定川芎嗪植入剂植入兔眼后玻璃体的浓度,考察其体内缓释行为,并对体内外相关性进行研究。结果:载药量为10%～30%时,可制备得到川芎嗪植入剂,含量均匀度符合2010年版《中国药典》规定。体外释放符合零级释放模型。以PL-GA 5050,2.5A为载体,载药量为30%的川芎嗪植入剂在玻璃体内可缓慢释放药物达到3周以上,体内外释放相关性良好。结论:热熔融挤出法制备川芎嗪眼部植入剂工艺可行,川芎嗪眼部植入剂在兔眼玻璃体内释药平稳,缓释效果良好。

Objective： To prepare ligustrazine （TMPZ） ocular sustained-release implant, and investigate its in vitro drug re- lease, pharmacokinetics in rabbit vitreum and in vitro correlation. Method： Ligustrazine ocular sustained-release implants were pre- pared by micro-twin conical screw mixers with hot-melting extrusion method, with polyactic-co-glycolic acid （PLGA） as the matrix. HPLC was adopted to determine the concentration in vitreum after ligustrazine was implanted in rabbit eyes, in order to examine its in vivo sustained-release behavior, and study the correlation between in vitro and in vivo. Result： Ligustrazine implants were prepared with a drug-loading rate between 10% and 30%, which was in conformity to the pharmacopoeia in terms of the content uniformity. Its in vitro release was in conformity to the zero-order release model. With PLGA 5050, 2. 5A as a vector, ligustrazine implants with a drug-loading rate of 30% could slowly release drug for more than 3 weeks, indicating a good correlation between in vitro and in vivo re- lease. Conclusion： Ligustrazine ocular implants prepared with hot-melting extrusion method is practicable. Ligustrazine ocular im- plants release drug smoothly in rabbit vitreous vitreums, suggesting good sustained-release effect.