Solid formulation of a supersaturable self-microemulsifying drug delivery system for valsartan with improved dissolution and bioavailability.

Solid formulation of a supersaturable self-microemulsifying drug delivery system for valsartan with improved dissolution and bioavailability.

Yeom, Dong Woo;Chae, Bo Ram;Kim, Jin Han;Chae, Jun Soo;Shin, Dong Jun;Kim, Chang Hyun;Kim, Sung Rae;Choi, Ji Ho;Song, Seh Hyon;Oh, Dongho;Sohn, Se Il;Choi, Young Wook;
oncotarget 2017 Vol. 8 pp. 94297-94316
406
yeom2017solidoncotarget

Abstract

In order to improve the dissolution and oral bioavailability of valsartan (VST), and reduce the required volume for treatment, we previously formulated a supersaturable self-microemulsifying drug delivery system (SuSMEDDS) composed of VST (80 mg), Capmul MCM (13.2 mg), Tween 80 (59.2 mg), Transcutol P (59.2 mg), and Poloxamer 407 (13.2 mg). In the present study, by using Florite PS-10 (119.1 mg) and Vivapur 105 (105.6 mg) as solid carriers, VST-loaded solidified SuSMEDDS (S-SuSMEDDS) granules were successfully developed, which possessed good flow properties and rapid drug dissolution. By introducing croscarmellose sodium (31 mg) as a superdisintegrant, S-SuSMEDDS tablets were also successfully formulated, which showed fast disintegration and high dissolution efficiency. Preparation of granules and tablets was successfully optimized using D-optimal mixture design and 3-level factorial design, respectively, resulting in percentage prediction errors of <10%. In pharmacokinetic studies in rats, the relative bioavailability of the optimized granules was 107% and 222% of values obtained for SuSMEDDS and Diovan powder, respectively. Therefore, we conclude that novel S-SuSMEDDS formulations offer great potential for developing solid dosage forms of a liquefied formulation such as SuSMEDDS, while improving oral absorption of drugs with poor water solubility.

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