CRYSTALLIZATION CONDITIONS AND PHYSICOMECHANICAL PROPERTIES OF IBUPROFEN-EUDRAGIT(R) S100 SPHERICAL CRYSTAL AGGLOMERATES PREPARED BY THE SOLVENT-CHANGE TECHNIQUE

Spherical crystal agglomeration of ibuprofen was performed in the pres ence of Eudragit(R) S100 using the solvent-change (ethanol-water) meth od and applying different crystallisation conditions such as initial s upersaturation under both increasing and constant drug:polymer ratios and different rates of stirring and cooling. The temperature in the cr ystallisation liquid and water consumption were recorded to determine the effects of polymer presence on crystallisation parameters (drug lo ading efficiency, crystal yield and mean 'apparent crystal growth' rat e) and to correlate them with the physicomechanical properties of the agglomerates. It was found that crystal yield and drug loading efficie ncy are not affected by the crystallisation conditions, while the mean 'apparent crystal growth' rate increases with initial supersaturation ratio and stirring rate; however, the cooling effect is stirring depe ndent, probably due to changes in the nucleation mechanism. The partic le size of agglomerates decreases, while sphericity, surface roughness and intraparticle porosity increase with polymer presence. Also, part icle size and sphericity decrease, while intraparticle porosity increa ses with initial supersaturation. The effects of Eudragit(R) addition on the fundamental particle properties are attributed to the habit and growth rate changes of ibuprofen microcrystals, as well as to their c oating before binding into spherical agglomerates. The stirring rate e ffect on particle size is enhanced by slow cooling, and sphericity bec omes maximal at slow cooling and fast stirring. The size and sphericit y changes due to stirring and cooling are attributed to the polymer bi nding ability and to detachment of small fragments from the agglomerat e surface. Flow or packing behaviour and densification of agglomerates at low compression are determined by the sphericity changes and their yield pressure by the brittleness due to the incorporated polymer. (C ) 1998 Elsevier Science B.V. All rights reserved.