Inclusion of Medium-Chain Triglyceride in Lipid-Based Formulation of Cannabidiol Facilitates Micellar Solubilization In Vitro, but In Vivo Performance Remains Superior with Pure Sesame Oil Vehicle.
Inclusion of Medium-Chain Triglyceride in Lipid-Based Formulation of Cannabidiol Facilitates Micellar Solubilization In Vitro, but In Vivo Performance Remains Superior with Pure Sesame Oil Vehicle.
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DOI：
10.3390/pharmaceutics13091349
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发表时间：
2021-08-27
期刊：
影响因子：
5.4
通讯作者：
Gershkovich P
中科院分区：
文献类型：
--
作者：
Feng W;Qin C;Cipolla E;Lee JB;Zgair A;Chu Y;Ortori CA;Stocks MJ;Constantinescu CS;Barrett DA;Fischer PM;Gershkovich P
口服芝麻油制剂有助于将水溶性较差的药物大麻二酚（CBD）输送到淋巴系统和血液循环。然而，这种天然油基制剂也导致CBD吸收的相当大的变化。在这项工作中，使用CBD作为模型药物，在体外和体内测试了在芝麻油溶媒中添加中链甘油三酯（MCT）或表面活性剂的脂质制剂的性能。体外脂解表明，添加MCT导致CBD更高地分布到胶束相中。向含MCT的制剂中进一步添加表面活性剂并不能改善药物在胶束相中的分布。在体内，含有MCT的制剂导致血清、淋巴和MLN中CBD浓度较低或相似，但变异性降低。MCT改善CBD的乳化和胶束增溶，但表面活性剂并没有进一步促进脂解的速率和程度。尽管添加MCT降低了变异性，但使用纯天然油溶剂时，淋巴转运和全身生物利用度的体内性能仍具有上级优势。
Oral sesame oil-based formulation facilitates the delivery of poorly water-soluble drug cannabidiol (CBD) to the lymphatic system and blood circulation. However, this natural oil-based formulation also leads to considerable variability in absorption of CBD. In this work, the performance of lipid-based formulations with the addition of medium-chain triglyceride (MCT) or surfactants to the sesame oil vehicle has been tested in vitro and in vivo using CBD as a model drug. The in vitro lipolysis has shown that addition of the MCT leads to a higher distribution of CBD into the micellar phase. Further addition of surfactants to MCT-containing formulations did not improve distribution of the drug into the micellar phase. In vivo, formulations containing MCT led to lower or similar concentrations of CBD in serum, lymph and MLNs, but with reduced variability. MCT improves the emulsification and micellar solubilization of CBD, but surfactants did not facilitate further the rate and extent of lipolysis. Even though addition of MCT reduces the variability, the in vivo performance for the extent of both lymphatic transport and systemic bioavailability remains superior with a pure natural oil vehicle.
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