Depth Profiling of Compression-Induced Disorders and Polymorphic Transition on Tablet Surfaces with Grazing Incidence X-ray Diffraction

Abstract

The present study proved that grazing incidence X-ray diffraction is a potential novel research tool to reveal crystallographic transformations taking place on the surfaces of the tablets induced, for example, by compression pressure.

Investigation of Solid Phase Composition on Tablet Surfaces by Grazing Incidence X-ray Diffraction

“…To understand variation in the phase transformation at the different regions of the tablets, depth profiling was carried out. In pharmaceutical context, GIXD has been employed previously to study phase transformation during dissolution (31) and compaction (22) and to evaluate effective penetration depth of X-rays in the tablets (32). In the current work, the potential of GIXD was further extended to evaluate the difference in stability of the different solid forms of three model drug substances towards the compaction.…”

“…For indomethacin and chlorpropamide, it has been observed that compaction leads to polymorphic transformation as well as amorphization (19)(20)(21). Compaction-induced amorphization was also observed for carbamazepine form III and tolbutamide form I (22). Two solvates of celecoxib, dimethyl acetamide and dimethyl formamide, have been shown to undergo desolvation during compaction (23).…”

“…The GIXD technique is unique in the sense that it can provide detailed information on the phase composition at the different depths parallel to the tablet surface (22,(30)(31)(32). As the surface is the first part of the tablet that comes into contact with dissolution medium, information on the surface layer is important with respect to the initial dissolution of the tablet.…”

Polymorphism and Solvatomorphism 2006

“…203 These changes were found to be localized on the surfaces of the tablets, and their degree decreased as a function of distance from the tablet surface. Samples of dry chlorpropamide Form-A were subjected to high pressure (5.5 GPa), but no evidence for a phase transition to Form-C could be obtained.…”

Evaluation of Effects of Pharmaceutical Processing on Structural Disorders of Active Pharmaceutical Ingredient Crystals Using Nanoindentation and High-Resolution Total Scattering Pair Distribution Function Analysis

“…During the manufacturing of drug products containing crystalline active pharmaceutical ingredients (APIs), drug crystals are often subjected to unit operations such as milling and compaction. It is well documented that these pharmaceutical processes can generate various types of defects in API crystals . These crystal defects represent regions of higher disorder and higher energy relative to the average overall energy of the crystalline material .…”