Agglomeration state and migration of drugs in wet granulations during drying

Migration of drugs was studied during drying of wet granules, agglomerated at pendular and funicular state (S-3 and S-4). Granulating liquids of diffe rent viscosity (2.5 and 7.5 mPa s) and drugs and diluents of different solu bility and wettability were employed and correlation was sought between dis tribution of the liquid, wet kneading parameters (torque and liquid consump tion S%), solid-liquid interactions (work of adhesion and spreading coeffic ients) and the migration of drugs. It was found that drug migration, expres sed as CV% of its content, was strongly dependent on the type of diluent. A lso, the type of diluent exerted the strongest effect on torque and liquid consumption during wet kneading and a significant one on moisture content o f the final granulations. Viscosity of the granulating liquid and molecular weight of the binder had no effect on liquid consumption but viscosity had a significant one on drug migration. Significant linear relationships were found between spreading coefficients and the liquid consumption (S%) at th e mid-state of funicular agglomeration (S-3 + S-4)/2 or the torque at the c apillary state S-5. Migration of drug was remarkably lower for drying in th e microwave oven and increased from the pendular (S-3) to the funicular (S- 4) agglomeration state when drying in conventional oven was applied. Linear relationships were found between migration (CV%) and the spreading coeffic ient of liquid on solid, lambda (LS), for the low and the high viscosity le vels of the granulating liquid, with r = 0.965, P = 0.05 and r = 0.901, P = 0.10, respectively. Also, a general linear relationship (r = 0.903 and P = 0.002) accommodating all experimental data was found between migration (CV %) and the ratio lambda (LS)/viscosity. Drug migration increases with solub ility and may become a problem in a range higher than 1 g in 148-400 ml of granulating liquid. (C) 2001 Elsevier Science BN. All rights reserved.