Flocculation of Polymer Stabilized Nanocrystal Suspensions to Produce Redispersible Powders

Abstract

Aqueous suspensions of crystalline naproxen nanoparticles, formed by antisolvent precipitation, were flocculated with sodium sulfate, filtered, and dried to form redispersible powders for oral delivery. The particles were stabilized with polyvinylpyrrolidone (PVP K-15) and/or poly(ethylene oxide-b-propylene oxide-b-ethylene oxide) (poloxamer 407). The yield of the drug in the powder was typically 92–99%, and the drug loading was reproducible to within 1–2%. The filtration process increased the drug loading by up to 61% relative to the initial value, as unbound surfactant was removed with the filtrate. Upon redispersion of the dried powder, the average particle size measured by light scattering was comparable to the original value in the aqueous suspension prior to flocculation, and consistent with primary particle sizes observed by scanning electron microscopy (SEM). For 300-nm particles, up to 95% of the drug dissolved in 2 min. The dissolution rate was correlated linearly with the specific surface area calculated from the average particle diameter after redispersion. The redispersion of dried powders was examined as a function of the salt concentration used for flocculation and the surfactant composition and concentration. Flocculation followed by filtration and drying is an efficient and highly reproducible process for the rapid recovery of drug nanoparticles to produce wettable powders with high drug loading and rapid dissolution.

Keywords:

• salt flocculation
• nanoparticles
• naproxen
• antisolvent precipitation
• dissolution

Acknowledgments

The authors would like to gratefully acknowledge the financial support from The Dow Chemical Company (Midland, MI, USA), partial support from the STC Program of the National Science Foundation under Agreement No. CHE-9876674, the Welch Foundation and from the Process Science and Technology Center at the University of Texas.