A Raman Spectroscopic Study of Solid Dispersions and Co-crystals During the Pharmaceutical Hot melt Extrusion Process

Abstract

Process Analytical Technology (PAT) is framed with the objective of the design and development of processes to ensure predefined quality of the product at the end of manufacturing. PAT implementation includes better understanding of process, reduction in production time with use of in-line, at-line and on-line measurements, yield improvement and energy and cost reductions. Hot Melt Extrusion process (HME) used in the present work is proving increasingly popular in industry for its continuous and green processing which is beneficial over traditional batch processing. The present work was focused on applications of Raman spectroscopy as off - line and in - line monitoring techniques as a PAT for production of pharmaceutical solid dispersions and co-crystals. Solid dispersions (SDs) of the anti-convulsant Carbamazepine (CBZ) with two pharmaceutical grade polymers have been produced using HME at a range of drug loadings and their amorphous nature confirmed using a variety of analytical techniques. Off-line and in-line Raman spectroscopy has been shown to be suitable techniques for proving preparation of these SDs. Through calibration curves generated from chemometric analysis in-line Raman spectroscopy was shown to be more accurate than off-line measurements proving the quantification ability of Raman spectroscopy as well as a PAT tool. Pure co-crystals of Ibuprofen-Nicotinamide and Carbamazepine-Nicotinamide have been produced using solvent evaporation and microwave radiation techniques. Raman spectroscopy proved its superiority over off-line analytical techniques such as DSC, FTIR and XRD for co-crystal purity determination adding to its key advantage in its ability to be used as an in-line, non-destructive technique.