title: Experimental and modelistic approach to explain granulate inhomogeneity through preferential growth.
abstract: Wet granulation of a powder mixture often leads to accumulation of the smallest particles in the large granules. The preferential uptake of these particles results in an inhomogeneous granulate. The aim of this study was to investigate the mechanism of preferential growth. For that purpose the growth of one single granule was followed by adding a droplet of binder liquid to a rotating powder mixture of paracetamol and lactose. The particle sizes of both components were varied. At various time points mass and paracetamol content of the granule was determined. The results showed in all cases that the fine particles have a relatively higher presence in the granule than the coarse particles. These observations were independent of the fact whether the fine particles consists of lactose or paracetamol. During layering growth of the granule, caused by radial penetration of the liquid, fine particles appear to have a higher affinity for growth than coarse particles. It was argued that small particles penetrate the pores of the granule more easily than large particles, leading to the preferential absorption of the fine constituents. A model based on this growth mechanism, was able to predict the experimental results. It was concluded that this non-random growth process underlies the formation of inhomogeneous granules.
authors.affiliation: Department of Pharmaceutics, N.V. Organon, AKZO-NOBEL, Room RK2216, P.O. Box 20, 5340 BH Oss, The Netherlands. kaspar.vandendries@organon.com
authors.forename: Kaspar
authors.initials: K
authors.lastname: van den Dries
authors.forename: Herman
authors.initials: H
authors.lastname: Vromans
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000493:pharmacokinetics; D000465:Algorithms; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding; D005079:Excipients; D007785:Lactose; D008956:Models, Chemical; D010316:Particle Size; D016062:Porosity; D011208:Powders / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet
chemical_list: D018712:Analgesics, Non-Narcotic; D005079:Excipients; D011208:Powders; D000082:Acetaminophen; D007785:Lactose