Preparation and Evaluation of High Dispersion Stable Nanocrystal Formulation of Poorly Water‐Soluble Compounds by Using Povacoat

In this study, we reported the application of Povacoat®, a hydrophilic polyvinylalcohol copolymer, as a dispersion stabilizer of nanoparticles of poorly water‐soluble compounds. In addition, the influence of aggregation of the nanoparticles on their solubility and oral absorption was studied. Griseofulvin (GF) was used as a model compound with poor water solubility and was milled to nanoparticles by wet bead milling. The dispersion stability of GF milled with Povacoat® or the generally used polymers (polyvinylalcohol, hydroxypropylcellulose SSL, and polyvinylpyrrolidone K30) was compared. Milled GF suspended in Povacoat® aqueous solution with D‐mannitol, added to improve the disintegration rate of freeze‐dried GF, exhibited high dispersion stability without aggregation (D90 = ca. 0.220 μm), whereas milled GF suspended in aqueous solutions of the other polymers aggregated (D90 > 5 μm). Milled GF with Povacoat® showed improved aqueous solubility and bioavailability compared with the other polymers. The aggregation of nanoparticles had significant impact on the solubility and bioavailability of GF. Povacoat® also prevented the aggregation of the various milled poorly water‐soluble compounds (hydrochlorothiazide and tolbutamide, etc.) more effectively than the other polymers. These results showed that Povacoat® could have wide applicability to the development of nanoformulations of poorly water‐soluble compounds. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3772–3781, 2014