Development, Characterization and in vivo evaluation of Tovaptan solid dispersions via solvent evaporation technique

Ramesh K, Chandra Shekar B, Khadgapathi P, D.V.R.N Bhikshapathi, Renuka K

Abstract


Investigation on in vitro and in vivo behavior of solid dispersions containing Tolvaptan is the focus of the present research work. The effect of various hydrophilic polymers on the aqueous solubility was studied. Kleptose HPB was selected as carrier and solid dispersions were prepared by solvent evaporation technique. Evaluation of solid dispersion for percentage yield, drug content and solubility was most appropriate. Solid dispersions of drug: Kleptose HPB: SLS (1:2:1 ratio) (SE8) shown higher dissolution rate i.e. 96.8 % compared with and pure drug (39.6%) and other formulations.  Differential scanning calorimetry and powder X-ray diffraction performed on solid dispersion showed that Tolvaptan existed in the amorphous form within the solid dispersion formulation fabricated using the solvent evaporation process. Additionally, scanning electron microscopy studies suggested the conversion of crystalline Tolvaptan to an amorphous form. In vivo studies of pure drug and optimized formulation (SE8) were carried out in male Wistar rats and pharmacokinetic parameters   calculated using Kinetica software 2000.  In vivo studies revealed that a marked increase in dissolution and bioavailability was exhibited by optimized Tolvaptan solid dispersion (SE8).  AUC (0-t) was increased more than 2.11 folds, Cmax increased about 2.67 folds and tmax reduced by 1 hour, when compared to the pure drug. Thus, the study has illustrated the potential use of a solid dispersion system for the delivery of a very poorly soluble drug tolvaptan with a better bioavailability. Therefore, the solid dispersions prepared by solvent evaporation method using Kleptose HPB as hydrophilic carrier can be successfully used for improvement of dissolution of Tolvaptan and resulted in faster onset of action as indicated by in vivo studies.


Keywords


Tolvaptan, hydrophilic carriers, solvent evaporation technique, solubility, solid dispersions

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