Optimization of solid self-dispersing micelle for enhancing dissolution and oral bioavailability of valsartan using Box-Behnken design.

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.

Development of Valsartan Floating Matrix Tablets Using Low Density Polypropylene Foam Powder: In vitro and In vivo Evaluation.

The main purpose of the study was to develop valsartan floating tablets (VFT) via non-effervescent technique using low density polypropylene foam powder, carbopol, and xanthan gum by direct compression. Before compression, the particulate powdered mixture was evaluated for pre-compression parameters. The prepared valsartan tablets were evaluated for post-compression parameters, swelling index, floating lag time, in vitro buoyancy studies, and in vitro and in vivo X-ray imaging studies in albino rabbits. The result of all formulations for pre- and post-compression parameters were within the limits of USP. FTIR and DSC studies revealed no interaction between the drug and polymers used. The prepared floating tablets had good swelling and floating capabilities for more than 12 h with zero floating lag time. The release of valsartan from optimized formulation NF-2 showed sustained release up to 12 h; which was found to be non-Fickian release. Moreover, the X-ray imaging of optimized formulation (NF-2) revealed that tablet was constantly floating in the stomach region of the rabbit, thereby indicating improved gastric retention time for more than 12 h. Consequently, all the findings and outcomes have showed that developed valsartan matrix tablets could be effectively used for floating drug delivery system.

Preparation and evaluation of valsartan by a novel semi-solid self-microemulsifying delivery system using Gelucire 44/14.

The aim of the present study was to develop a novel semi-solid self-microemulsifying drug delivery system (SMEDDS) using Gelucire(®) 44/14 as oil with strong solid character to improve the oral bioavailability of poorly soluble drug valsartan. The solubility of valsartan in various excipients was determined, the pseudo-ternary phase diagram was constructed in order to screen the optimal excipients, and DSC analysis was performed to evaluate the melting point of SMEDDS. The optimal drug-loaded SMEDDS formulation was consisted of 30% Gelucire(®) 44/14 (oil), 40% Solutol(®) HS 15 (surfactant), and 30% Transcutol(®) P (cosurfactant) (w/w) with 80 mg valsartan/g excipients. The average droplet sizes of the optimized blank and drug-loaded SMEDDS formulations were 26.20 ± 1.43 and 33.34 ± 2.15 nm, and the melting points of them were 35.6 and 36.8 °C, respectively. The in vitro dissolution rate of optimal semi-solid SMEDDS was increased compared with commercial capsules, resulting in the 2.72-fold and 2.97-fold enhancement of Cmax and AUC0-t after oral administration in rats, respectively. These results indicated that the novel semi-solid SMEDDS formulation could potentially improve the oral bioavailability of valsartan, and the semi-solid SMEDDS was a desirable system than the traditional liquid SMEDDS because it was convenient for preparation, storage and transportation due to semi-solid state at room temperature and melted state at body temperature.