Optimization of solid self-dispersing micelle for enhancing dissolution and oral bioavailability of valsartan using Box-Behnken design
- Authors
- Goo Y.T.; Park S.Y.; Chae B.R.; Yoon H.Y.; Kim C.H.; Choi J.Y.; Song S.H.; Choi Y.W.
- Issue Date
- 30-Jul-2020
- Publisher
- Elsevier B.V.
- Keywords
- Box-Behnken design; Dissolution; Oral bioavailability; Reduced quantity; Solid self-dispersing micelle; Valsartan
- Citation
- International Journal of Pharmaceutics, v.585, pp 1 - 11
- Pages
- 11
- Journal Title
- International Journal of Pharmaceutics
- Volume
- 585
- Start Page
- 1
- End Page
- 11
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/42772
- DOI
- 10.1016/j.ijpharm.2020.119483
- ISSN
- 0378-5173
1873-3476
- Abstract
- A novel solid self-dispersing micelle (S-SDM) was developed to enhance the oral bioavailability of valsartan (VST) and to reduce the total mass of solidified supersaturable self-microemulsifying drug delivery system (S-SuSMEDDS), composed of Capmul MCM, Tween 80 (T80), Gelucire 44/14 (G44), Poloxamer 407, Florite PS-10 (FLO), and low-substituted hydroxypropyl cellulose B1 (HPC). Excluding oil component from S-SuSMEDDS, S-SDM was optimized using a Box-Behnken design with three independent variables: X1 (T80/G44, 0.63), X2 (FLO/HPC, 0.41), and X3 (solid carrier, 177.6 mg); and three response factors: Y1 (droplet size, 191.9 nm), Y2 (dissolution efficiency at 15 min, 55.0%), and Y3 (angle of repose, 32.4°). The desirability function was 0.636, showing an excellent agreement between the predicted and experimental values. With approximately 75% weight of S-SuSMEDDS, no distinct crystallinity of VST was observed in S-SDM, resulting in critical micelle concentration value of 32 μg/mL. Optimized S-SDM showed an approximate 4-fold improved dissolution (pH 1.2, 500 mL) compared with raw VST. Following oral administration in rats, optimized S-SDM improved relative bioavailability by approximately 235%, 216%, and 127% versus raw VST, Diovan® (commercial reference), and S-SuSMEDDS, respectively. Thus, optimized S-SDM could be a selectable candidate for developing water-insoluble drugs in reduced quantity. © 2020 Elsevier B.V.
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