Benita S, Friedman D, Weinstock M
J Pharm Pharmacol. 1986 Sep;38(9):653-8. doi: 10.1111/j.2042-7158.1986.tb03104.x.
Physostigmine was incorporated in an injectable emulsion in an attempt to prolong its pharmacological activity. Emulsions which remained stable over 6 month storage were prepared using optimal experimental conditions. The in-vitro kinetic examination revealed that the rate-determining step in the release process of physostigmine from the emulsion was its partitioning from the oily phase to the external aqueous phase. The in-vivo results indicated that the physostigmine emulsion was able to inhibit the cholinesterase activity for only 1 to 2 h. The preliminary pharmacokinetic analysis showed that the physostigmine emulsion apparently increased the bioavailability compared with the conventional injectable solution. This could be attributed either to the protection of the sensitive drug from the enzymatic degradation or to improved absorption. The presence of poloxamer micelles in the aqueous phase was shown to enhance the bioavailability of physostigmine without having any effect on its pharmacological activity or duration.
毒扁豆碱被制成注射用乳剂，以期延长其药理活性。采用最佳实验条件制备了在6个月储存期内保持稳定的乳剂。体外动力学研究表明，毒扁豆碱从乳剂中释放过程的限速步骤是其从油相分配到外部水相。体内结果表明，毒扁豆碱乳剂仅能抑制胆碱酯酶活性1至2小时。初步药代动力学分析表明，与传统注射溶液相比，毒扁豆碱乳剂的生物利用度明显提高。这可能归因于对敏感药物的酶降解保护或吸收改善。水相中泊洛沙姆胶束的存在被证明可提高毒扁豆碱的生物利用度，而对其药理活性或持续时间无任何影响。
