Inline UV/Vis spectroscopy as PAT tool for hot-melt extrusion

Abstract

Hot-melt extrusion on co-rotating twin screw extruders is a focused technology for the production of pharmaceuticals in the context of Quality by Design. Since it is a continuous process, the potential for minimizing product quality fluctuation is enhanced. A typical application of hot-melt extrusion is the production of solid dispersions, where an active pharmaceutical ingredient (API) is distributed within a polymer matrix carrier. For this dosage form, the product quality is related amongst others to the drug content. This can be monitored on- or inline as critical quality attribute by a process analytical technology (PAT) in order to meet the specific requirements of Quality by Design. In this study, an inline UV/Vis spectrometer from ColVisTec was implemented in an early development twin screw extruder and the performance tested in accordance to the ICH Q2 guideline. Therefore, two API (carbamazepine and theophylline) and one polymer matrix (copovidone) were considered with the main focus on the quantification of the drug load. The obtained results revealed the suitability of the implemented PAT tool to quantify the drug load in a typical range for pharmaceutical applications. The effort for data evaluation was minimal due to univariate data analysis, and in combination with a measurement frequency of 1 Hz, the system is sufficient for real-time data acquisition.

Novel Cleaning-in-Place Strategies for Pharmaceutical Hot Melt Extrusion

“…In the regime of higher concentrations, in which the absorption peak was higher than the dynamic range of the detector, a procedure similar to Ref. [27] was performed on a subset of wavelengths. To evaluate the latter regime, an integration of the shoulder of the absorption peak between 300 and 370 nm was proportional to the concentration and, thus, used for the prediction.…”

“…To reduce the CV effort, HME would greatly benefit from in-line processes that assess the cleanliness of the material and equipment. Although ultraviolet-visible (UV–Vis) spectroscopy has been shown to be highly applicable to in-line analyses in HME [ 26 , 27 , 28 , 29 , 30 ], e.g., for monitoring the API content [ 30 ], to date no scientific study has employed UV–Vis spectroscopy to detect the API in terms of cleanliness of a material and/or processing equipment. In addition, it is not certain, if an API-free material that is mainly analysed by in-line techniques such as UV–Vis spectroscopy, can also represent an API-free processing equipment [ 9 ], since contaminated material might be trapped in dead spots of the equipment [ 31 ] and contribute to cross-contamination.…”

An update on the contribution of hot-melt extrusion technology to novel drug delivery in the twenty-first century: part I

“…Wesholowski et al [49] used in-line UV/VIS spectrophotometry as a PAT tool for manufacturing solid dispersions of carbamazepine and theophylline with copovidone. The method was proved to be accurate and repeatable for the formulations tested.…”

Process knowledge discovery tools in compliance with Quality by Design concept.

“…Hot Melt Extrusion, HME). Niemiecki zespół badawczy opisał niestandardowe wykorzystanie spektroskopii UV-Vis jako nieinwazyjnego narzędzia do monitorowania zawartości substancji czynnych w ekstrudatach uzyskanych techniką wytłaczania na gorąco [15].…”