Implementation of transmission NIR as a PAT tool for monitoring drug transformation during HME processing

Abstract

The aim of the work reported herein was to implement process analytical technology (PAT) tools during hot melt extrusion (HME) in order to obtain a better understanding of the relationship between HME processing parameters and the extruded formulations. For the first time two in-line NIR probes (transmission and reflectance) have been coupled with HME to monitor the extrusion of the water insoluble drug indomethacin (IND) in the presence of Soluplus (SOL) or Kollidon VA64 hydrophilic polymers. In-line extrusion monitoring of sheets, produced via a specially designed die, was conducted at various drug/polymer ratios and processing parameters. Characterisation of the extruded transparent sheets was also undertaken by using DSC, XRPD and Raman mapping. Analysis of the experimental findings revealed the production of molecular solutions where IND is homogeneously blended (ascertained by Raman mapping) in the polymer matrices, as it acts as a plasticizer for both hydrophilic polymers. PCA analysis of the recorded NIR signals showed that the screw speed used in HME affects the recorded spectra but not the homogeneity of the embedded drug in the polymer sheets. The IND/VA64 and IND/SOL extruded sheets displayed rapid dissolution rates with 80% and 30% of the IND being released, respectively within the first 20min.

Continuous twin-screw granulation for enhancing the dissolution of poorly water soluble drug

“…Raman mapping (Lee et al, 2011;Islam et al, 2015)was performed using a Jobin/YvonLabRam 320 instrument equipped with an Olympus microscope (Horiba, Japan)…”

Continuous manufacturing via hot-melt extrusion and scale up: regulatory matters

“…[44]. [DE26]Process parameter chart during a scale-up via hot melt-extrusion (HME) [72]. Using the batch monitoring data and process information to predict the quality of the product PAT Level V Feedback control of the process to maintain the quality of the product…”

“…It has been found that, with the increase in screw speed from 50 rpm to 400 rpm (temperature constant) during a scale-up, the torque increased from 8.8 Nm to 12.7 Nm, impacting the resultant SMEC values, which exhibited a significant effect on the state of the extrudates [72]. Similarly, the increasing screw speed favored intense mixing inside the barrel by increasing the pressure (8 bars) and the torque (12.7 Nm).…”

Advanced surface chemical analysis of continuously manufactured drug loaded composite pellets

“…The existence of the single phase homogenous system in all formulations indicates that the drug molecule has been encapsulated within the polymeric matrices. This could also happen due to the molecular interaction as a result of single-phase distribution [30].…”