Production, physicochemical investigations, antioxidant effect, and cellular uptake in Caco-2 cells of the supersaturable astaxanthin self-microemulsifying tablets

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.

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Materials

Astaxanthin (CAS Number: 472-61-7) with at least 98% purity was purchased from Hangzhou DayangChem Co., Ltd. (Hangzhou, China). A food-grade rice bran (RB) oil was purchased from a local supermarket in Bangkok, Thailand. Kolliphor® RH 40 and Span® 20 were imported from BASF (Germany) and TCI (Tokyo Chemical Industry Co., Ltd., Japan), respectively. Microcrystalline cellulose (MCC; Avicel® PH-101) and hydroxypropyl methylcellulose (HPMC, E grade; HPMC-E5) were imported by Onimax Co., Ltd. (Thailand). Polyvinyl alcohol (PVA 8/88) was bought from Merck KGaA (Darmstadt, Germany). 1,1-diphenyl-2-picryl-hydrazil (DPPH), N-acetyl-L-cysteine (NAC), 2′,7′-dichloro-fluorescin diacetate (DCFH2-DA), dimethyl sulfoxide (DMSO), and coumarin 6 (C6) were purchased from Sigma-Aldrich (St. Louis, MO, USA). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT, Invitrogen™) and Hoechst33342 (Invitrogen™) were purchased from Thermo Fisher Scientific. HPLC-grade organic solvents including acetonitrile, dichloromethane, and methanol were purchased form Honeywell® (Republic of Korea)

Wai Thet Aung, Hnin Ei Ei Khine, Chatchai Chaotham, Veerakiet Boonkanokwong,
Production, physicochemical investigations, antioxidant effect, and cellular uptake in Caco-2 cells of the supersaturable astaxanthin self-microemulsifying tablets, European Journal of Pharmaceutical Sciences, Volume 176,  2022, 106263, ISSN 0928-0987, https://doi.org/10.1016/j.ejps.2022.106263.