The utilization of surface free-energy parameters for the selection of a suitable binder in fluidized bed granulation

Surface free energy was determined for model substances pentoxyfilline, acy clovir, lactose and binding agents (that were used in the granulation proce ss) hydroxypropilmethyl cellulose (HPMC) and polyvinylpyrrolidone (PVP) wer e determined by contact angle measurements. The methods of Wu, Good-van Oss and Della Volpe were used for solid-surface flee-energy calculation. Sprea ding coefficients (S) were calculated and correlated with granulate propert ies. Granulates consisted of model drug and binding agent, and were produce d in fluid bed granulator Glatt powder coater granulator GPCG1 by means of spraying the colloidal solution of binder on the model substance. Granules contained either 5% or 10% binder. Inverse granules, however, were also pro duced by spraying the model drug (i.e. pentoxyfilline and lactose) on the b inding agent (HPMC, PVP). Particle size distribution, friability, true dens ity. bulk density and tapped density of the granulates were determined. Alt hough many different parameters influence the granule properties, it has be en found that the interactions between the drug and the binder play a very important role. Spreading coefficients were found to be in good correlation with the friability of granulates. Positive spreading coefficient values o f the binder over the model substance correlate well with the low friabilit y of the granules containing lower amount of binder, i.e. 5%. In the group of the same binder, the spreading coefficient values decrease fi om pentoxy filline over lactose to acyclovir. Friability results show that, for the sy stem under consideration, PVP offers certain advantages over the grade of H PMC employed. The increase of the binder amount from 5 to 10% resulted in m ore friable granulates. Lower work of cohesion of the binder (PVP and HPMC) than the work of adhesion between binder and the model substances is consi dered responsible for the higher friability of the granules. The inverse gr anulation process, where the suspension of the model substance was sprayed over the solid binder particles. proved mole efficient with HPMC than with PVP. According to the spreading coefficient results. the binder should spre ad over the drug. However, the kinetics of wetting appears to play an impor tant role in the granulation process. According to these results, the concl usion was made that water wets HPMC much faster than PVP. (C) 2000 Elsevier Science B.V. All rights reserved.