Polymorphic Transformation of Indomethacin during Hot Melt Extrusion Granulation: Process and Dissolution Control

Pharmaceutical Research
Ting XuKenneth Morris

Abstract

To study and elucidate the effect of the intensity and duration of processing stresses on the possible solid-state changes during a hot melt extrusion granulation process. Blends of α-indomethacin and PEG 3350 (w/w 4:1) were granulated using various screw sizes/designs on the melt extruder under different temperature regimes. Differential Scanning Calorimetry and X-ray Powder Diffraction were employed for characterization. The dissolution behavior of the pure polymorphs and the resulting granules was determined using in-situ fiber optic UV testing system. An XRPD quantitation method using Excel full pattern fitting was developed to determine the concentration of each constituent (amorphous, α and γ indomethacin and PEG) in samples collected from each functioning zone and in granules. Analysis of in-process samples and granules revealed that higher temperature (≥130°C) and shear stress accelerated the process induced phase transitions from amorphous and/or the α form to γ indomethacin during heating stage. However, rapid cooling resulted in an increased percentage of the α form allowing isolation of the meta-stable form. By determining the conditions that either prevent or facilitate process induced transformations of IMC polymo...Continue Reading

References

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Citations

Feb 14, 2020·Current Pharmaceutical Design·Beiqian TianHongxun Hao
Nov 30, 2018·Pharmaceutical Research·Qi Tony Zhou, Tonglei Li
May 21, 2019·Pharmaceutical Development and Technology·Yuri Ikeuchi-TakahashiHiraku Onishi
Apr 4, 2021·Pharmaceutics·Manali Banerjee, Blair Brettmann

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Methods Mentioned

BETA
X-ray
Differential Scanning Calorimetry

Software Mentioned

Smartlab
Excel
RotaVapor
Smartlab Guidance
Excel Solver
Mercury
PDXL
Smartlab Studio

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