Formulation and In Vivo Evaluation of a Solid Self-Emulsifying Drug Delivery System Using Oily Liquid Tocotrienols as Model Active Substance

Self-emulsifying drug delivery systems (SEDDS) can improve the oral bioavailability of poorly water-soluble drugs. Solid self-emulsifying drug delivery systems (s-SEDDS) offer several advantages including improved drug stability, ease of administration, and production. Most compounds employed in developing s-SEDDS are solid in nature, with a high amount of surfactants added. The aim of this study was to develop an s-SEDDS using a tocotrienol-rich fraction (TRF) as the model liquid active substance via a simple adsorption method. The solid formulation was developed using magnesium aluminosilicate as the carrier with 70% TRF and 30% surfactants (poloxamer and Labrasol^®). The formulation showed good self-emulsification efficiency with stable emulsion formed, excellent powder flowability, and small emulsion droplet size of 210–277 nm. The s-SEDDS with combined surfactants (poloxamer and Labrasol^®) showed a faster absorption rate compared to preparations with only a single surfactant and enhanced oral bioavailability (3.4–3.8 times higher) compared to the non-self-emulsifying oily preparation when administered at a fasted state in rats. In conclusion, an s-SEDDS containing a high amount of TRF was successfully developed. It may serve as a useful alternative to a liquid product with enhanced oral bioavailability and the added advantage of being a solid dosage form.

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Materials

A tocotrienol-rich fraction (TRF) was obtained from Excelvite (Ipoh, Malaysia). According to the manufacturer’s certificate of analysis (COA), TRF contained 7.1%, 20.6%, and 13.9% of delta-, gamma-, and alpha-tocotrienol, respectively. The TRF content was periodically analysed to ensure its level according to the COA prior to use. The rest of the TRF consisted mainly of alpha-tocopherol, palm olein, plant squalene, and sterol complex, with traces of carotenoid complexes. The excipients used in the experiments were generously provided by Hovid Ltd., Ipoh, Malaysia. They were Aerosil^® 200 (colloidal silicon dioxide; Evonik, Essen, Germany), Avicel^® (Microcrystalline cellulose (MCC) PH 101, PH 102, PH 112, and PH200; FMC Biopolymer, Philadelphia, PA, USA), StarCap^® (corn starch; Colorcon, Dartfort, UK), Fujicalin^® (dibasic calcium phosphate; Fuji Chemical Industry Co., Toyama, Japan), Klucel™ (hydroxypropyl cellulose HPC LF and EXF; Ashland, Wilmington, DE, USA), Methocel™ (hydroxypropyl methylcellulose HPMC E5, E15, K100 PLV, K4M; Colorcon, Dartfort, UK), GranuLac^® 100 (lactose monohydrate; MEGGLE, Wasserburg, Germany), LYCATAB^® (maltodextrin; Roquette, Lestrem, France), Starch 1500^® (pregelatinised starch; Colorcon, Dartfort, UK), Aqualon™ (sodium carboxymethylcellulose (CMC), Ashland, Wilmington, DE, USA), Ac-Di-Sol^® (croscarmellose sodium; FMC Biopolymer, Philadelphia, PA, USA), Labrasol^® (caprylocaproyl macrogol-8 glycerides; Gattefossé, Saint-Priest, France), and sodium lauryl sulfate (SLS; BASF, Los Angeles, CA, USA). Poloxamer 188 was obtained from BASF (Los Angeles, CA, USA). Neusilin US2 (magnesium aluminosilicate) was obtained from Fuji Chemical Industry Co. (Toyama, Japan). Solvents, either analytical or HPLC grades, were from Merck Life Sciences (Darmstadt, Germany). Tocovid Suprabio™ was obtained from Hovid Ltd., Ipoh, Malaysia.

Lee, Y.Z.; Seow, E.K.; Lim, S.C.; Yuen, K.H.; Abdul Karim Khan, N. Formulation and In Vivo Evaluation of a Solid Self-Emulsifying Drug Delivery System Using Oily Liquid Tocotrienols as Model Active Substance. Pharmaceutics 2021, 13, 1777. https://doi.org/10.3390/pharmaceutics13111777

excipients formulation