PharmaMV software platform from Perceptive Engineering performs automated dynamic DOE tests
24 January 2018
Hot melt extrusion (HME), a manufacturing technique traditionally used in the plastic and food industries, now attracts significant interest from the pharmaceutical manufacturing sector. Primarily, this is because HME enables the continuous manufacture of a wide variety of dosage formulations, including solid dose form, which is of particular importance for poorly soluble APIs. Other advantages of HME technology include the ability to incorporate inline process analytical technology (PAT) – enabling a quality by design (QbD) approach to continuous manufacturing – and the capacity to process a wide range of excipients, many of which cannot be processed using established manufacturing techniques.
In this work, a set of design of experiment (DOE) tests were carried out and analysed on the HME process using a water-soluble amorphous polymer. The DoE tests consider screw speed and barrel zone temperature as factors and their impact is analysed using a multivariate model. The principal component analysis identifies well-defined clustering associated with different screw speeds and operating temperatures. Furthermore, the statistical analysis also provides information regarding the variations in the material viscosity and its causal effect on the HME motor power/torque. This multivariate analysis demonstrates that the HME process lends itself to critical process monitoring and fault detection, not only in the context of extrudate quality but also for further downstream processing such as milling and 3-D printing of tablets.
AFFINISOL HPMC 15LV HME,2 a water-soluble amorphous polymer with a molecular weight of less than 100kDa, bulk density of 0.42kg/L and D(0,5) of 104.49μm, was used within the HME DoE tests. Hot melt extrusion was carried out using Thermo Fisher Scientific’s Eurolab 16 – a 16mm co-rotating twin-screw extruder (Figure 1). The PharmaMV software platform, from Perceptive Engineering, was connected to the HME unit to perform automated dynamic DOE tests. Process setpoints (eg, zone temperatures and screw speed) were adjusted in line with the DoE factorial table, with the process and analytical data aligned and collated through the PharmaMV platform. To facilitate the DoE trials, a user interface was also developed to control the process with PharmaMV.
Inline PAT tools can also be integrated with the HME process to support a QbD approach to continuous manufacturing. Perceptive Engineering, in collaboration with CMAC, as part of the REMEDIES project has developed a multivariate analysis and monitoring scheme for the pharmaceutical HME process. The scheme monitors various key process/material parameters within the HME, which is important for successful downstream 3-D printing of tablets from the extrudate.
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