Nanoparticles of poorly water-soluble drugs were prepared in suspension via antisolvent precipitation in order to improve their dissolution behaviour. Insoluble, surface-functionalized, micron-range, clay carrier particles were employed for the dual purpose of stabilizing the nanoparticles in suspended state, and facilitating their unhindered isolation to solid state; often a challenging step in nanoparticle production. The carrier particles, which were functionalized with an optimal level of cationic polymer (protamine), attracted negatively-charged nanoparticles to their surface as a uniform and segregated nanoparticle layer, at drug loadings up to 9% w/w. By using carrier particles to stabilise the nanoparticles on their surface, the traditionally used solubilised nanosuspension stabilisers could be eliminated, thus avoiding time-consuming stabiliser screening tests. The carrier particle system facilitated stabilisation of nanoparticles in suspension, isolation of nanoparticles to the solid state via filtration, and preservation of fast nanoparticle-induced dissolution rates of the dried nanoparticle-carrier composites, indicating preservation of their high surface area during drying. The process was validated with two poorly water-soluble BCS Class II drugs, fenofibrate and mefenamic acid, both of which demonstrated negative surface charge in aqueous suspension.
Keywords: Antisolvent precipitation; Bioavailability; Carrier particles; Dissolution rate; Drug nanoparticles; Filtration.
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