Modification of ketoprofen bead structure produced by the spherical crystallization technique with a two-solvent system

Abstract

Poorly-compressible crystals of ketoprofen were agglomerated by the spherical crystallization technique with a two-solvent system (acetone/demineralized water). In order to study a possible modification of particle texture, spherical crystals were formulated with low concentrations of additives. The results showed that the procedure was possible with ethylcellulose, cross-linked PVP and cross-linked CMC, all at a concentration of 1%. However, no spherical beads could be obtained with the water-soluble compounds tested (PVP and Eudragit L100-55®), Eudragit RS100® and colloidal silica. These formulation trials have indicated two main factors with their possible influences: the polymer solubility and viscosity in the solvent/non-solvent system leading to two kinds of nucleation and changes in mass transfer and drug/polymer interactions leading to the formation of reversible complexes or irreversible complexes and possibility of drug release modifications. Moreover, formulations with the methacrylic acid derivatives were found to be incompatible with the operating conditions, in terms of temperatures changes, stirring or residence time. Furthermore, an optimization of the formulation with ethylcellulose yielded a controlled release form with 1% of the polymer, whereas the addition of very low concentrations increased the drug release.