How does hot melt extrusion complement Quality by Design?
One major paradigm in QbD is the shift from batch to continuous processing. Continuous processing spreads risk out over time, without dramatically decreasing throughput, rather than depending on the success of a single, largescale batch. Such processes are also easier to adjust and control effectively in real time.One continuous processing technology that is receiving considerable attention from the pharma industry is hot melt extrusion (HME). HME combines multiple batched unit operations such as granulation and blending into a single process and, in some cases, may also remove the need for drying materials. HME involves processing polymeric materials above their glass transition temperature (Tg) to effect molecularlevel mixing of thermoplastic binders and/or polymers and actives. The technique is a combination of melting and mechanical granulation, and gives many advantages over batch processes, including highthroughput, dust reduction and high precision. Crucially, it is possible to instantly respond to out of specification results without affecting an entire product run.
Using significantly reduced mixing volumes, HME rapidly homogenises excipients and APIs, while continuously delivering final product. In particular, the technology has been emerging as a way to address poor API stability; it does not create hydrolyic stress during processing and it also negates the need for a drying step. It has also been shown to enhance dissolution properties and bioavailability via preparation of a solid dispersion.1,2 Additionally, it is possible for users to monitor specific HME process parameters such as temperature, the speed of the screws and the gravity feed rate of the component materials, which are all critical to produce a product that is within specification.
How can FT-NIR be used to predict HME component concentrations in real time?
As with many continuous processes, HME can be readily coupled with online Fourier Transform Near Infrared (FT-NIR) spectroscopy. This allows for real time feedback and control (a significant part of PAT and the larger paradigm of QbD) of the chemical composition of the extruded materials, leading to enhanced control of the HME process itself. FTNIR spectroscopy has proven extremely effective as a PAT tool for many applications including tablet content uniformity and online moisture quantification in a fluid bed dryer.3,4 FT-NIR measures the vibrational response of molecules in a sample using a white light source and provides a spectroscopic fingerprint that can be used to distinguish one molecule from another. The innately low absorbances of the technique allows for long pathlength measurements through traditionally infrared-opaque media and NIR light can also be efficiently transmitted through optical fiber, which means the point of analysis can be up to 100 m away from the analyser.
FT-NIR is well suited to monitor and control hot melt extruders as it is rapid without being destructive. FT-NIR also eliminates the need for sample preparation and doesn't require the use of solvents or consumables. It is capable of measuring component concentrations, as well as strict physical properties such as average particle size. It is readily adaptable to any environment through the use of customised probes.