Study on formability of solid nanosuspensions during nanodispersion and solidification: I. Novel role of stabilizer/drug property

Few or no attempts have been made so far to understand the feasibility of solid nanosuspension formulation during nanodispersion and solidification in terms of drug properties and stabilizer characterizations. In order to establish a knowledge base about the effect of physicochemical property of drug compounds and stabilizers on solid nanosuspension production during nanodispersion and solidification, a comparative study was firstly performed on 10 different stabilizers at 3 concentrations for 8 structurally different drug compounds. Synthetic polymers (HPMC, PVP K30, CMS-Na and MC) displayed a poor stabilizing performance (10% success rate on average) during nanodispersion, but polymers showed better potential when higher concentrations was applied during freezing and lyophilization. Meanwhile, an effect for the surfactants group was even more pronounced during nanodispersion. However, the solid nanosuspension stabilized by surfactants showed the worst formability potential when be applied in setted concentrations during freezing and lyophilization. From the point of view of drug property, it was found that the surface hydrophobicity and cohesive energy of drug, were responsible for the formability of the solid nanosuspension during nanodispersion and solidification. Wetting index (k) and Delta E were concluded to have a direct correlation on the feasibility of formation of a stable solid nanosuspension, which can give a formulation design strategy from where candidate drugs and stabilizers with a set of properties. (c) 2013 Elsevier B.V. All rights reserved.