Mandar V. Dali

The effect of the physical states of binders on high‐shear wet granulation and granule properties: A mechanistic approach towards understanding high‐shear wet granulation process. part I. physical characterization of binders

In this study, the objective is to investigate the effect of the physical state of a binder on wet granulation and granule properties using a binary model system (CaCO(3)-binder), which is essential for understanding the mechanism of wet granulation when binder is added in a dry state. Part I focus on studying the phase behavior or the physical state change of four binders: PVP K12, K29/32, HPC, and HPMC, after exposure to either moisture or liquid water. Their interaction with water was studied by measuring the water sorption of binders and the binary blends of CaCO(3)-binder. Changes in the physical states of the binders at room temperature as a function of water content was monitored via dialysis experiments, and characterized by determining the glass transition temperatures (T(g)) of the binders with water. The results suggest that the PVP binders can absorb more water than the cellulosic binders which is same for binder alone and in the binary blends. PVP K12 undergoes a phase transition from the glassy state to the rubbery/solution state at much lower water content than PVP K29/32 (10% vs. 20%) at room temperature. The phase transition for HPC occurs with 10-15% water based on rheological measurements.

Determination of mass transfer dissolution rate constants from critical time of dissolution of a powder sample

This article presents a method for obtaining mass transfer dissolution rate constants of polydisperse, particulate solids under given hydrodynamic conditions. Oxalic acid, salicylic acid, and phthalimide were recrystallized and classified into various mesh cuts, which were then subjected to dissolution in a USP dissolution apparatus II. Expressions were derived for the anticipated dissolution profiles, and it is shown that cube root plots should show a nick at the point were the smallest particle dissolves. Time and microscopic dimensions then allow calculation of the mass transfer dissolution rate constant.

The Effect of the Physical States of Binders on High-Shear Wet Granulation and Granule Properties: A Mechanistic Approach Toward Understanding High-Shear Wet Granulation Process. Part II. Granulation and Granule Properties

The objective is to provide mechanistic understanding of a preferred wet granulation process that a binder is added in a dry state. Blends of CaCO(3) and binders were prepared and used as model systems, and they were exposed to either 96% RH (rubbery/solution state) or 60% RH (glassy state) at room temperature to control the physical state of the binders, followed by high-shear granulation and particle size measurement. The blends of PVP K12, PVP K29/32, and HPC showed a significant increase in particle size after exposure to 96% RH. An increase of aspect ratio was also observed for the blend of HPC. In contrast, the blends being exposed to 60% RH did not exhibit any increase in particle size or aspect ratio. Regarding the effect of binder molecular weight on the mechanical strength of granules, granules of PVP K29/32 had higher strength than granules of PVP K12. This can be explained using polymer entanglement theory, in which the degree of polymerization (DP) of (N ∼ 440-540) of PVP K29/32 is above the critical value (N(c)  ∼ 300-600) for entanglement; while DP of PVP K12 (N ∼ 20-30) is below it. Finally, a water sorption-phase transition-diffusion induced granule growth model for granulation has been suggested.