Hot melt extrusion technology for continuous manufacturing
Hot melt extrusion (HME), a manufacturing technique traditionally used in the plastic and food industries, is now attracting significant interest from the pharmaceutical manufacturing sector. This is primarily 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.1 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.
Multivariate analysis on the HME process
Formulation development using HME requires an understanding of material properties as the excipient makes its way through the HME barrel…