Aung Wai Thet, Khine Hnin Ei Ei, Chaotham Chatchai, Boonkanokwong Veerakiet
Graduate Program of Pharmaceutical Sciences and Technology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, 254 Phayathai Road, Wang Mai, Pathum Wan, Bangkok 10330, Thailand.
Graduate Program of Pharmaceutical Sciences and Technology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand; Department of Biochemistry and Microbiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
Eur J Pharm Sci. 2022 Sep 1;176:106263. doi: 10.1016/j.ejps.2022.106263. Epub 2022 Jul 16.
The purpose of this study was to develop astaxanthin (AST)-loaded self-microemulsifying drug delivery system (SMEDDS) tablets and evaluate their physicochemical and biological properties. The optimized liquid (L)-AST SMEDDS formulation was composed of rice bran oil (33.67%), Kolliphor® RH 40 (34.70%), and Span® 20 (31.63%). Two types of hydrophilic polymers (hydroxypropyl methylcellulose, HPMC, and polyvinyl alcohol, PVA) solutions were selected as a precipitation inhibitor for AST and incorporated into L-AST SMEDDS to obtain supersaturation and enhance dissolution of AST. The formulation was then mixed with microcrystalline cellulose and subsequently transformed to solid S-AST SMEDDS particles using a spray dryer prior to direct compression into tablets. The HPMC AST SMEDDS tablet and PVA AST SMEDDS tablet were characterized for their physicochemical properties, dissolution, AST release, and stabilities. Moreover, the cellular uptake and antioxidant effect of AST SMEDDS tablets were evaluated in Caco-2 cells. With good tablet characters, both HPMC AST SMEDDS tablet and PVA AST SMEDDS tablet dissolution profiles were improved compared to that of raw AST. While initially less than 50% of AST released from HPMC AST SMEDDS tablet and PVA AST SMEDDS tablet in pH 1.2 medium, after 6 h more than 98% of AST releases in pH 6.8 were achieved which was similar to L-AST SMEDDS profile. Cellular antioxidant activities of L-AST SMEDDS and HPMC AST SMEDDS tablet & PVA AST SMEDDS tablet were significantly greater than pure AST powder. HPMC AST SMEDDS tablet showed better uptake and deeper penetration through Caco-2 cells than that in PVA AST SMEDDS tablet and pure powder. Our successfully developed AST SMEDDS tablets were demonstrated to be a potential platform to deliver highly lipophilic AST and improve permeation and bioavailability.
本研究的目的是开发负载虾青素（AST）的自微乳化药物递送系统（SMEDDS）片剂，并评估其物理化学和生物学性质。优化后的液体（L）-AST SMEDDS制剂由米糠油（33.67%）、聚氧乙烯氢化蓖麻油RH 40（34.70%）和吐温20（31.63%）组成。选择两种亲水性聚合物（羟丙基甲基纤维素，HPMC，和聚乙烯醇，PVA）溶液作为AST的沉淀抑制剂，并将其加入到L-AST SMEDDS中以获得过饱和状态并增强AST的溶解。然后将该制剂与微晶纤维素混合，随后使用喷雾干燥器将其转化为固体S-AST SMEDDS颗粒，再直接压片制成片剂。对HPMC AST SMEDDS片剂和PVA AST SMEDDS片剂的物理化学性质、溶出度、AST释放和稳定性进行了表征。此外，还评估了AST SMEDDS片剂在Caco-2细胞中的细胞摄取和抗氧化作用。HPMC AST SMEDDS片剂和PVA AST SMEDDS片剂均具有良好的片剂特性，与原料药AST相比，两者的溶出曲线均得到改善。在pH 1.2介质中，HPMC AST SMEDDS片剂和PVA AST SMEDDS片剂最初释放的AST不到50%，但在pH 6.8介质中6小时后，AST的释放率超过98%，这与L-AST SMEDDS的曲线相似。L-AST SMEDDS、HPMC AST SMEDDS片剂和PVA AST SMEDDS片剂的细胞抗氧化活性均显著高于纯AST粉末。HPMC AST SMEDDS片剂在Caco-2细胞中的摄取和穿透能力优于PVA AST SMEDDS片剂和纯粉末。我们成功开发的AST SMEDDS片剂被证明是一种潜在的平台，可用于递送高度亲脂性的AST，并提高其渗透性和生物利用度。
