The Impact of Shear Stress on Compression-nduced Polymorphic Transformation in Tablets and the Creation of Strategies to Minimize It

Abstract

Our objective was to ascertain the effects of (i) hydrostatic pressure alone and (ii) hydrostatic pressure
combined with shear stress during compaction on the polymorphic transformation (form C / A) of
chlorpropamide, a generic drug. The powder was subjected to pressures ranging from 25 to 150 MPa
using a combination of hydrostatic pressure in a pressure vessel and tablet pressing. The overall quantity
of phase change was determined using powder X-ray diffractometry, and the distribution of phase
composition in tablets was quantified using 2D-XRD. Due to the presence of shear stress during
compaction, which was independent of pressure, the quantity of transformation that took place after
compaction exceeded expectations based on hydrostatic pressure alone. When compressed to 25 MPa,
the radical tablet surface and the core showed vastly different degrees of phase shift. This gradient
became smaller with increasing compression pressure. To mitigate the effects of compression-induced
phase change, four different approaches were considered: a cavity tablet, a ceramic-lined die, a site-
specific lubricant, and a viscoelastic excipient. The ceramic-lined die and site-specific lubrication
effectively decreased the amount of compression-induced phase shift.