Key considerations for optimization of formulation and melt-extrusion process parameters for developing thermosensitive compound

Abstract

The melt-extrusion process is currently applied in the pharmaceutical field in the manufacturing of a variety of dosage forms and formulations, including solid dispersions. Though this technology is considered efficient and continuous, there are potential challenges of which, additional thermal degradation of drug substance because heat stress and shear forces are of a primary concern. This paper attempts to understand the impact of thermal and/or mechanical components of the melt-extrusion process on the stability of a thermosensitive drug substance during scale-up. The overall degradation profile of the drug substance was correlated with the various physical changes made to the extruder as well as the process temperature. The results suggested that the degradation profile of a thermosensitive drug substance could be controlled by proper design of screw assemblies and by optimization of screw rotations per minute, process temperature, and feed rate during development and scale-up.

The utilization of drug–polymer interactions for improving the chemical stability of hot-melt extruded solid dispersions

“…All systems showed a negative free energy of mixing near the melting temperature, with the most negative value for DIF–PVP K30, followed by DIF–PVP VA64, DIF–HPMC and DIF–Soluplus systems sequentially. According to melting theory, the melting of a pure drug occurs at a temperature when the chemical potential of the crystalline drug is equal to that of the molten drug . At a constant pressure, the chemical potential is the partial molar Gibbs free energy.…”

“…Among the various techniques for preparing solid dispersions, hot‐melt extrusion (HME) has stood out with obvious advantages due to its single‐step, simple and organic solvent‐free preparation process, and gained increasing popularity . However, the elevated processing temperature has certainly limited the application of HME for heat‐sensitive drugs, and so far only a few number of studies focused on this problem …”

“…[6][7][8] However, the elevated processing temperature has certainly limited the application of HME for heat-sensitive drugs, and so far only a few number of studies focused on this problem. [9] In many cases, thermal degradation of drug is mainly related to the cumulative exposure to heat, which is a function of temperature and exposing duration. [10] Techniques such as the formation of cocrystal have been utilized to minimize the thermal degradation of drug.…”

Discovering and Developing Molecules with Optimal Drug-Like Properties

“…For instance, Ghosh et al used a statistical design of experiments controlling screw design and assembly, screw RPM, feed rate, and overall process temperature to optimize the degradation of a thermally liable active ingredient (Ghosh et al 2012). The authors were able to limit chemical degradation without the addition of a plasticizer to lower T g .…”

Thermal stability and thermal degradation kinetics of short and long glass fiber reinforced PA10T composites

“…. However, polymers are suffered from thermal, oxidative and light degradation during production and processing, as well as the application and recycling stages . The thermal degradation behavior of polymer composites is an important indicator in determining the maximum service temperature.…”