Solid formulation of a supersaturable self-microemulsifying drug delivery system for valsartan with improved dissolution and bioavailability
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Dong Woo Yeom1,*, Bo Ram Chae1,2,*, Jin Han Kim1, Jun Soo Chae1, Dong Jun Shin1, Chang Hyun Kim1, Sung Rae Kim1, Ji Ho Choi1, Seh Hyon Song2, Dongho Oh2, Se Il Sohn2 and Young Wook Choi1
1College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea
2Daewon Pharm. Co., Ltd, Seoul 04994, Republic of Korea
*These authors have contributed equally to this work
Young Wook Choi, email: firstname.lastname@example.org
Keywords: valsartan; SMEDDS; solid carrier; tablet; optimization
Received: June 27, 2017 Accepted: September 20, 2017 Published: October 09, 2017
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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