264452 Improved Recovery and Dissolution of Poorly Water-Soluble Drug Nanoparticles From Dried Nanocomposite Microparticles

Wednesday, October 31, 2012: 3:36 PM
Allegheny III (Westin )
Anagha Bhakay, Chemical engineering, New Jersey Institute of Technology, Newark, NJ, Mohammad Azad, Chemical, Biological, and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, NJ, Rajesh N. Dave, Chemical Engineering, New Jersey Institute of Technology, Newark, NJ and Ecevit Bilgili, Chemical, Biological and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, NJ

Incorporation of poorly water-soluble drug nanoparticles into solid dosage forms entails drying of nanosuspensions as an intermediate step, which can lead to loss of their large surface area and may lead to poor bioavailability. In this study, nanoparticle recovery of poorly water soluble drugs from nanocomposite microparticles (NCMPs) redispersed in water was investigated as a function of various excipients. Nanosuspensions of griseofulvin (GF), considered as a model poorly water soluble 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), their combinations at various concentrations and a superdisintegrant (croscarmellose sodium, CCS) were used as stabilizers during milling. The NCMPs obtained from the fluidized bed coating were redispersed in water using various methods of agitation to recover the GF nanoparticles. The redispersion methods studied had a slight impact on the recovery of the nanoparticles when SDS was present in the formulation. The HPC–SDS combination resulted in a synergistic effect in the formation of finer nanoparticles as well as in fast redispersion of the nanoparticles of five different poorly water soluble drugs from the NCMPs. Poor redispersion of the nanoparticles and slower dissolution were observed when SDS was removed from the formulations and addition of dispersants like mannitol also could not recover the GF nanoparticles. However, incorporation of a novel additive such as milled CCS and a mixture of milled/unmilled CCS led to enhanced GF nanoparticle recovery and dissolution rate from surfactant-free NCMPs.

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