Design, Optimization, Preparation and Evaluation of Dispersion Granules of Valsartan and Formulation into Tablets

Abstract

The objective of the present work undertaken was to enhance the solubility and dissolution rate of valsartan a poorly water soluble antihypertensive, by preparation of solid dispersion granules which would additionally allow easy compression into tablets. The dispersion granules were prepared using a hot melt granulation technique which involved preparation of a homogenous dispersion of valsartan in gelucire-50/13 melt, followed by its adsorption on to the surface of aeroperl-300pharma, an inert adsorbent. A two-factor, three-level (32) statistical design was implemented to quantitate the influence of gelucire-50/13 and aeroperl-300pharma on the dissolution profile and flow properties of the dispersion granules, where gelucire-50/13 and aeroperl-300pharma were chosen as independent variables, while dissolution and flow properties were chosen as dependent variables. The dispersion granules were characterized for their in-vitro dissolution rate and flow properties. An appropriate statistical model was arrived at and a significantly enhanced dissolution rate and flow properties were exhibited with the optimized formulation. The formulation was further characterized by FTIR, DSC, XRD and SEM analysis. FTIR spectrum revealed some drug excipient interactions. DSC and XRD data indicated the retention of amorphous form of valsartan. SEM confirmed the homogeneity and surface adsorption of the gelucire-50/13 melt on aeroperl-300pharma leading to enhanced surface area and thus dissolution rate. The tablets of optimized dispersion granules were formulated and evaluated. The in-vitro dissolution rate of these tablets was significantly better in comparison with marketed formulation. In conclusion the statistical model enabled us to understand the effects of formulation variables on the dispersion granules of valsartan.

Design and characterization of cefuroxime axetil biphasic floating minitablets

“…The SEM analysis of the samples was performed to investigate the surface morphology and homogeneity of surface of granules. The samples of optimized granules of IR and SR minitablets were sputter coated with gold at room temperature before examination to render the surface of particles electroconductive (Shrivastava et al, 2009). The SEM analysis of the granules was done by Jeol JSM-840 (Tokya, Japan) SEM.…”

Development, Optimization, and Characterization of Solid Self-Nanoemulsifying Drug Delivery Systems of Valsartan Using Porous Carriers

“…Several formulation approaches have already been employed such as inclusion complexes with cyclodextrin, solid dispersions, surfactants (5), lipidic excipients (6), and nanoparticles (7) to enhance the oral bioavailability of valsartan but yielded limited fruition due to their solubility enhancement characteristic alone (8). Lately, self-emulsifying drug delivery systems (SEDDS) are found to be highly promising technique to enhance the oral bioavailability of poorly watersoluble drugs by circumnavigation of the hepatic first-pass effect, metabolism by gut cytochrome-P450 family of isozymes, inhibition of P-gp efflux, protection of drug degradation in the gastric acidic environment and drug absorption through lymphatic pathways (9,10).…”

Improvement of Dissolution Rate of Valsartan by Solid Dispersion System Using D(−) Mannitol

“…Thus, the semicrystalline drug was embedded in the hydrophilic carrier and its solid state properties changed to amorphous one [10]. Previous studies have reported that disappearance of the characteristic endothermic peaks of the valsartan dispersed in Gelucire 50/13 is due to melting of the drug in the matrix [13].…”