Fabrication and evaluation of valsartan–polymer–surfactant composite nanoparticles by using the supercritical antisolvent process

Abstract

The aim of this study was to fabricate valsartan composite nanoparticles by using the supercritical antisolvent (SAS) process, and to evaluate the correlation between in vitro dissolution and in vivo pharmacokinetic parameters for the poorly water-soluble drug valsartan. Spherical composite nanoparticles with a mean size smaller than 400 nm, which contained valsartan, were successfully fabricated by using the SAS process. X-ray diffraction and thermal analyses indicated that valsartan was present in an amorphous form within the composite nanoparticles. The in vitro dissolution and oral bioavailability of valsartan were dramatically enhanced by the composite nanoparticles. Valsartan–hydroxypropyl methylcellulose–poloxamer 407 nanoparticles exhibited faster drug release (up to 90% within 10 minutes under all dissolution conditions) and higher oral bioavailability than the raw material, with an approximately 7.2-fold higher maximum plasma concentration. In addition, there was a positive linear correlation between the pharmacokinetic parameters and the in vitro dissolution efficiency. Therefore, the preparation of composite nanoparticles with valsartan–hydroxypropyl methylcellulose and poloxamer 407 by using the SAS process could be an effective formulation strategy for the development of a new dosage form of valsartan with high oral bioavailability.

Enhanced oral bioavailability of valsartan using a polymer-based supersaturable self-microemulsifying drug delivery system

“…2 In order to enhance the solubility and oral absorption of VST, various formulation approaches, such as solid dispersion, spray-dried emulsion, spray-dried nanosuspension, and supercritical antisolvent process, have been studied. [3][4][5][6] Self-microemulsifying drug delivery systems (SMEDDS) are widely known to overcome low solubility and poor oral absorption of water-insoluble drugs. In the gastrointestinal (GI) tract, they can form oil-in-water (o/w) microemulsions spontaneously, thus allowing rapid dissolution of drugs and enhancing permeation of the drugs across the intestinal membrane.…”

Preparation and Characterization of TPGS‐Colloidal Silica Microparticles for Enhancement of Solubility and Oral Bioavailability of Lercanidipine Hydrochloride

“…18 Similar to that for other drugs with poor water-solubility, the oral bioavailability of lercanidipine hydrochloride can be increased by in vitro dissolution induced by amorphous TPGS-colloidal silica microparticles. Furthermore, it is well known that TPGS may positively affect drug absorption by enhancing the solubility of poorly water-soluble drugs (via micellar solubilization) and the permeability of gastrointestinal epithelial cells, and by inhibiting P-glycoprotein (efflux transporter).…”

Recent advancement of gelatin nanoparticles in drug and vaccine delivery

“…This mechanism has been widely used in liposome and other polymer-mediated gene transfer [159][160][161][162][163]. The electrostatic-bound of DNA can be released from the GNP-DNA complexes in alkaline medium at pH >10 or by the presence of high salt concentrations (>2 mol/L sodium chloride) [84]. Leong et al [164] had studied the in vivo transfection efficiency of GNPs containing the LacZ plasmid in the tibialis anterior muscle of 6-week-old BALB/c mice.…”