Preparation and Pharmacokinetics Evaluation of Solid Self-Microemulsifying Drug Delivery System (S-SMEDDS) of Osthole
Preparation and Pharmacokinetics Evaluation of Solid Self-Microemulsifying Drug Delivery System (S-SMEDDS) of Osthole
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DOI：
10.1208/s12249-018-1067-3
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发表时间：
2018-05
影响因子：
3.3
通讯作者：
Chaojie Sun;Yun Gui;Rongfeng Hu;Jiayi Chen;Bin Wang;Yuxing Guo;Wenjie Lu;Xiangjiang Nie;Q. Shen;Song Gao;Wenyou Fang
中科院分区：
文献类型：
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作者：
Chaojie Sun;Yun Gui;Rongfeng Hu;Jiayi Chen;Bin Wang;Yuxing Guo;Wenjie Lu;Xiangjiang Nie;Q. Shen;Song Gao;Wenyou Fang
为提高难溶性药物蛇床子素的溶解度和口服生物利用度，采用球形结晶技术制备固体自微乳化给药系统（S-SMEDDS）。首先，通过筛选脂质体和乳化剂，以蓖麻油、Cremophor RH 40和1，2-丙二醇为原料，制备了蛇床子素液体自微乳化给药系统。通过单因素考察，进一步确定了S-SMEDDS中高分子材料、良溶剂、桥连剂和不良溶剂的种类和用量。最佳处方为乙基纤维素（EC）：Eudragit S100 = 1：2，分别作为基质形成聚合物和肠溶包衣聚合物。实验结果表明，以无水乙醇和二氯甲烷（5：3）为良溶剂，以0.08%SDS水溶液为不良溶剂，以二氯甲烷为桥连剂，以无水乙醇和二氯甲烷为桥连剂，以0.08%SDS水溶液为桥连剂。优化后的蛇床子素S-SMEDDS产率为83.91 ± 3.31%，包封率为78.39 ± 2.25%。其次，蛇床子素L-SMEDDS固化成蛇床子素S-SMEDDS，其形貌、粒径和zeta电位没有显著变化。体外释药实验表明蛇床子素S-SMEDDS具有较好的缓释效果。体内药物动力学研究表明，蛇床子素S-SMEDDS在家兔体内的Tmax和平均滞留时间（MRT（0-t））均显著延长，进一步证实了蛇床子素S-SMEDDS具有缓释作用。与蛇床子素水混悬液和L-SMEDDS相比，蛇床子素S-SMEDDS的生物利用度分别提高了205%和152%。结果表明，S-SMEDDS是一种有效的口服固体剂型，可提高难溶性药物蛇床子素的溶解度和口服生物利用度。
The study was performed aiming to enhance the solubility and oral bioavailability of poorly water-soluble drug osthole by formulating solid self-microemulsifying drug delivery system (S-SMEDDS) via spherical crystallization technique. Firstly, the liquid self-microemulsifying drug delivery system (L-SMEDDS) of osthole was formulated with castor oil, Cremophor RH40, and 1,2-propylene glycol after screening various lipids and emulsifiers. The type and amount of polymeric materials, good solvents, bridging agents, and poor solvents in S-SMEDDS formulations were further determined by single-factor study. The optimal formulation contained 1:2 of ethyl cellulose (EC) and Eudragit S100, which served as matrix forming and enteric coating polymers respectively. Anhydrous ethanol and dichloromethane with a ratio of 5:3 are required to perform as good solvent and bridging agent, respectively, with the addition of 0.08% SDS aqueous solution as poor solvent. The optimized osthole S-SMEDDS had a high yield (83.91 ± 3.31%) and encapsulation efficiency (78.39 ± 2.25%). Secondly, osthole L-SMEDDS was solidified to osthole S-SMEDDS with no significant changes in terms of morphology, particle size, and zeta potential. In vitro release study demonstrated a sustained release of the drug from osthole S-SMEDDS. Moreover, in vivo pharmacokinetic study showed that the Tmax and mean residence time (MRT(0-t)) of osthole were significantly prolonged and further confirmed that osthole S-SMEDDS exhibited sustained release effect in rabbits. Comparing with osthole aqueous suspension and L-SMEDDS, osthole S-SMEDDS increased bioavailability by 205 and 152%, respectively. The results suggested that S-SMEDDS was an effective oral solid dosage form, which can improve the solubility and oral bioavailability of poorly water-soluble drug osthole.