Recovery of BCS Class II drugs during aqueous redispersion of core–shell type nanocomposite particles produced via fluidized bed coating

Abstract

Incorporation of BCS Class II drug nanoparticles into solid dosage forms entails drying of nanosuspensions as an intermediate step, which can unfortunately lead to loss of their large surface area through size growth and/or agglomeration. Ensuing incomplete nanoparticle recovery and redispersion during dissolution of the solid dosage forms may lead to poor bioavailability. In this study, nanoparticle recovery from nanocomposite microparticles redispersed in water or an aqueous surfactant solution was investigated as a function of various excipients. Nanosuspensions of griseofulvin (GF), considered as a model BCS Class II drug, were prepared by wet media milling and subsequently dried through coating on Pharmatose® carrier particles in a fluidized bed processor. A polymer (hydroxypropyl cellulose, HPC), a surfactant (sodium dodecyl sulfate, SDS), and their combinations at various concentrations were used as stabilizers during milling; mannitol was used as dispersant in one formulation. The core–shell type nanocomposite microparticles obtained from the fluidized bed coating were redispersed in water using various methods of agitation to recover the GF nanoparticles. Particle size analysis, SEM imaging, and dissolution testing were used to elucidate the redispersion phenomenon and its relevance to dissolution. It was found that the presence of SDS was critical to the full recovery of nanoparticles and their dissolution, whereas HPC appeared to have positive yet convoluted effects. The redispersion methods studied had a slight impact on the recovery of nanoparticles when SDS was present either in the formulation or in the redispersion medium (water). Incomplete recovery of the nanoparticles caused relatively poor drug dissolution, signifying the importance of complete redispersion. The HPC–SDS combination resulted in a synergistic effect in the formation of finer nanoparticles as well as in fast redispersion of GF nanoparticles from the nanocomposite microparticles. A similar redispersion response was observed with another BCS Class II drug, phenylbutazone (PHB).