Carrier particle mediated stabilization and isolation of valsartan nanoparticles

Abstract

Drug nanoparticles are a promising solution to the challenging issues of low dissolution rates and erratic bioavailability due to their greater surface/volume ratio. The central purpose of this study is to prepare, stabilize and isolate nanoparticles of poorly water-soluble active pharmaceutical ingredients (APIs) into a dried form with the help of clay carrier particles. Isolation of nanoparticles from suspension into the dried state is crucial to avoid the problems of aggregation and Ostwald ripening. In this study nanoparticles of the API valsartan were generated via a reverse antisolvent process at high supersaturations. Montmorillonite (MMT) and protamine functionalized montmorillonite (PA-MMT) were employed for stabilization and isolation of the valsartan (Val) nanoparticles (ca. 50 nm) into a dried form. A high dissolution rate of the resultant solid formulation at high drug loadings (up to 33.3% w/w) was achieved. The dissolution rates of the isolated valsartan nanoparticle carrier composites (dried Val-MMT nanocomposites and dried Val-PA-MMT nanocomposites) were similar to that of freshly prepared suspended valsartan nanoparticles, confirming that the high surface area of the nanoparticles is retained during the adsorption and drying processes. Differential scanning calorimetry and PXRD studies indicated that the valsartan nanoparticles were amorphous when adsorbed onto the carrier particles. The dissolution rates of the Val-MMT and Val-PA-MMT nanocomposites were maintained after 10 months' storage which indicates that no aggregation or solid state transformation of the carrier-stabilized Val nanoparticles had occurred.

Keywords: Carrier particles; Dissolution rate; Drug nanoparticles; High loading; Isolation; Reverse antisolvent precipitation.