title: The development of a growth regime map for a novel reverse-phase wet granulation process.
abstract: The feasibility of a novel reverse-phase wet granulation process has been established and potential advantages identified. Granule growth in the reverse-phase process proceeds via a steady state growth mechanism controlled by capillary forces, whereas granule growth in the conventional process proceeds via an induction growth regime controlled by viscous forces. The resultant reverse-phase granules generally have greater mass mean diameter and lower intragranular porosity when compared to conventional granules prepared under the same liquid saturation and impeller speed conditions indicating the two processes may be operating under different growth regimes. Given the observed differences in growth mechanism and consolidation behaviour of the reverse-phase and conventional granules the applicability of the current conventional granulation regime map is unclear. The aim of the present study was therefore to construct and evaluate a growth regime map, which depicts the regime as a function of liquid saturation and Stokes deformation number, for the reverse-phase granulation process. Stokes deformation number was shown to be a good predictor of both granule mass mean diameter and intragranular porosity over a wide range of process conditions. The data presented support the hypothesis that reverse-phase granules have a greater amount of surface liquid present which can dissipate collision energy and resist granule rebound resulting in the greater granule growth observed. As a result the reverse-phase granulation process results in a greater degree of granule consolidation than that produced using the conventional granulation process. Stokes deformation number was capable of differentiating these differences in the granulation process.
authors: Technical Services/Manufacturing Science Division, Eli Lilly & Company, Indianapolis, IN, 46285, USA. Electronic address: wade_jonathan@lilly.com.
authors: Jonathan B
authors: JB
authors: Wade
authors: King's College London, Institute of Pharmaceutical Science, London, SE1 9NH, UK.
authors: Gary P
authors: GP
authors: Martin
authors: Technical Services/Manufacturing Science Division, Eli Lilly & Company, Indianapolis, IN, 46285, USA.
authors: David F
authors: DF
authors: Long
mesh_terms: D004339:Drug Compounding / Q000379:methods*; D017886:Durapatite / Q000737:chemistry*; D010316:Particle Size; D016062:Porosity; D011205:Povidone / Q000737:chemistry*; D011208:Powders / Q000737:chemistry*
chemical_list: D011208:Powders; D017886:Durapatite; D011205:Povidone
keywords: Growth regime map; Intragranular porosity; Reverse-phase granulation; Stokes deformation number; Wet granulation