ELSEVIER International Journal of Pharmaceutics 144 (1996) 195 207 international journal of pharmaceutics Modification of ketoprofen bead structure produced by the spherical crystallization technique with a two-solvent system A. Ribardi6re*, P. Tchoreloff, G. Couarraze, F. Puisieux Laboratoire de Physique Pharmaceutique, URA CNRS 1218, Facultd de Pharmacie de Paris-Sud, 5, Rue Jean Baptiste Clement, 92290 Chdtenay- Malabry, France Received 30 May 1996; revised 3 September 1996; accepted 12 September 1996 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 RSI00 ~ 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. Copyright © 1996 Elsevier Science B.V. Ke)'words: Ketoprofen: Particle structure; Polymers; Spherical crystallization; Texture 1. Introduction The direct tableting technique has been success- * Corresponding author. Tel.: + 33 l 46835610; fax: + 33 1 fully applied to numerous drugs on the industrial 46835312: e-mail: ribardie@psisun.u-psud.fr scale. However, when the mechanical properties 0378-5173/96/$15.00 Copyright ~) 1996 Elsevier Science B.V. All rights reserved PII S0378-5173(96)04746- 1