Wang Tao, Shen Liao, Sun Lijun, Zhang Yadan, Li Haiyan, Wang Yongan, Quan Dongqin
State Key Laboratory of Toxicology and Medical Countermeasure Beijing Institute of Pharmacology and Toxicology Beijing China.
309 Hospital of PLA Beijing China.
Food Sci Nutr. 2019 Sep 27;7(11):3675-3680. doi: 10.1002/fsn3.1224. eCollection 2019 Nov.
Classical mixed micelle systems make excellent parenteral drug carriers for lipophilic or poorly soluble drugs, but many formulations details are not fully understood and need further study. Thus, we constructed mixed micelle systems with lecithin and either glycocholic acid sodium salt or deoxycholic acid sodium salt in order to investigate the differences between the bile salts. Vitamin K, a lipid-soluble drug, was encapsulated in the mixed micelles, and the influence of bile salts on the quality and stability of the mixed micelle systems was analyzed. Both bile salts displayed similar profiles, and the amounts of bile salts used in formulating clear solutions did not differ. Mixed micelle systems formed from glycocholic acid sodium were physically stable at low pH levels (5.5), whereas those formed from deoxycholic acid required higher pH (>8.5). High pH levels hurt active pharmaceutical ingredients that are prone to hydrolytic and oxidative degradation. Hence, when mixed micelle systems formed from deoxycholic acid sodium were sterilized, unexpected chemical unstability occurred. Therefore, we conclude that glycocholic acid sodium salt is more suitable than deoxycholic acid sodium salt for the preparation of mixed micelle injections.
经典混合胶束系统是亲脂性或难溶性药物理想的肠胃外给药载体，但许多制剂细节尚未完全明晰，仍需进一步研究。因此，我们构建了由卵磷脂与甘氨胆酸钠盐或脱氧胆酸钠盐组成的混合胶束系统，以研究这两种胆盐之间的差异。将脂溶性药物维生素K包封于混合胶束中，并分析胆盐对混合胶束系统质量和稳定性的影响。两种胆盐呈现出相似的特性，且配制澄清溶液时所用胆盐的量并无差异。由甘氨胆酸钠形成的混合胶束系统在低pH值（5.5）时物理性质稳定，而由脱氧胆酸形成的混合胶束系统则需要更高的pH值（>8.5）。高pH值会损害易于发生水解和氧化降解的活性药物成分。因此，当对由脱氧胆酸钠形成的混合胶束系统进行灭菌时，会出现意想不到的化学不稳定性。所以，我们得出结论，甘氨胆酸钠盐比脱氧胆酸钠盐更适合用于制备混合胶束注射液。
