Effect of High-Pressure Homogenization on the Formulation of Micro- and Nanocrystals

Specially engineered drug particles can solve solubility and formulation problems, which are major challenges for the pharmaceutical industry. Particle size reduction of poorly water soluble drugs results in increased dissolution rate and higher bioavailability or better processability as demonstrated in previous studies [1, 2]. High-pressure homogenization can be used to decrease particle size, since it induces cavitation forces and causes highly localized increase in temperature and pressure within the fluid, resulting in decrease of particle size and inhibition of agglomeration. The current study is focused on properties inherent to particle engineering as well as methods for production and characterization of microand nanocrystals. The meloxicam, a low molecular weight analgetic for oral administration, exhibits a slow dissolution, therefore, it was formulated as microor nanosized particles by high-pressure homogenization. The samples were freeze-dried and characterized regarding particle size, morphology, structural analyses (DSC, XRPD) and in vitro dissolution rate. The final formulations were free of organic solvent and contained micro(4–8 μm) or nano-sized (400–1000 nm) meloxicam crystals. Meloxicam in vitro dissolution rate was significantly improved and its particle size was found to be dependant on stabilizers used. To conclude, the new meloxicam formulations can potentially expand its application also to alternative administration routes (e. g. pulmonary and intranasal). This work was supported by TÁMOP-Hungary research project: Development of teranostics in cardiovascular, metabolics, and inflammatory diseases (TÁMOP4.2.2-08/1-2008-0013).