scholarly journals In-Line UV-Vis Spectroscopy as a Fast-Working Process Analytical Technology (PAT) during Early Phase Product Development Using Hot Melt Extrusion (HME)

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 166 ◽  
Author(s):  
Walkiria Schlindwein ◽  
Mariana Bezerra ◽  
Juan Almeida ◽  
Andreas Berghaus ◽  
Martin Owen ◽  
...  
Keyword(s):  
Product Development ◽  
Feed Rate ◽  
Early Phase ◽  
Hot Melt Extrusion ◽  
Continuous Manufacturing ◽  
Melt Extrusion ◽  
Screw Speed ◽  
Vis Spectroscopy ◽  
Solid Feed Rate ◽  
Hot Melt

This paper displays the potential of an in-line PAT system for early phase product development during pharmaceutical continuous manufacturing following a Quality by Design (QbD) framework. Hot melt extrusion (HME) is used as continuous manufacturing process and UV–Vis spectroscopy as an in-line monitoring system. A sequential design of experiments (DoE) (screening, optimisation and verification) was used to gain process understanding for the manufacture of piroxicam (PRX)/Kollidon® VA64 amorphous solid dispersions. The influence of die temperature, screw speed, solid feed rate and PRX concentration on the critical quality attributes (CQAs) absorbance and lightness of color (L*) of the extrudates was investigated using multivariate tools. Statistical analysis results show interaction effects between concentration and temperature on absorbance and L* values. Solid feed rate has a significant effect on absorbance only and screw speed showed least impact on both responses for the screening design. The optimum HME process conditions were confirmed by 4 independent studies to be 20% w/w of PRX, temperature 140 °C, screw speed 200 rpm and feed rate 6 g/min. The in-line UV-Vis system was used to assess the solubility of PRX in Kollidon® VA64 by measuring absorbance and L* values from 230 to 700 nm. Oversaturation was observed for PRX concentrations higher than 20% w/w. Oversaturation can be readily identified as it causes scattering in the visible range. This is observed by a shift of the baseline in the visible part of the spectrum. Extrudate samples were analyzed for degradation using off-line High-Performance Liquid Chromatography (HPLC) standard methods. Results from off-line experiments using differential scanning calorimetry (DSC), and X-ray diffraction (XRD) are also presented.

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

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 588
Author(s):  
Martin Spoerk ◽  
Ioannis Koutsamanis ◽  
Josip Matić ◽  
Simone Eder ◽  
Carolina Patricia Alva Zúñiga ◽  
...  
Keyword(s):  
Hot Melt Extrusion ◽  
Production Equipment ◽  
Process Equipment ◽  
Melt Extrusion ◽  
Release Formulation ◽  
Sustained Release Formulation ◽  
Cleaning Procedure ◽  
Vis Spectroscopy ◽  
First Time ◽  
Hot Melt

To avoid any type of cross-contamination, residue-free production equipment is of utmost importance in the pharmaceutical industry. The equipment cleaning for continuous processes such as hot melt extrusion (HME), which has recently gained popularity in pharmaceutical applications, necessitates extensive manual labour and costs. The present work tackles the HME cleaning issue by investigating two cleaning strategies following the extrusion of polymeric formulations of a hormonal drug and for a sustained release formulation of a poorly soluble drug. First, an in-line quantification by means of UV–Vis spectroscopy was successfully implemented to assess very low active pharmaceutical ingredient (API) concentrations in the extrudates during a cleaning procedure for the first time. Secondly, a novel in-situ solvent-based cleaning approach was developed and its usability was evaluated and compared to a polymer-based cleaning sequence. Comparing the in-line data to typical swab and rinse tests of the process equipment indicated that inaccessible parts of the equipment were still contaminated after the polymer-based cleaning procedure, although no API was detected in the extrudate. Nevertheless, the novel solvent-based cleaning approach proved to be suitable for removing API residue from the majority of problematic equipment parts and can potentially enable a full API cleaning-in-place of a pharmaceutical extruder for the first time.

scholarly journals Evaluation of Hot-Melt Extrusion and Injection Molding for Continuous Manufacturing of Immediate-Release Tablets

2015 ◽  
Vol 104 (6) ◽  
pp. 1971-1980 ◽  
Author(s):  
Alice Melocchi ◽  
Giulia Loreti ◽  
Maria Dorly Del Curto ◽  
Alessandra Maroni ◽  
Andrea Gazzaniga ◽  
...  
Keyword(s):  
Injection Molding ◽  
Immediate Release ◽  
Hot Melt Extrusion ◽  
Continuous Manufacturing ◽  
Melt Extrusion ◽  
Hot Melt

Hot-Melt Extrusion: a Roadmap for Product Development

2021 ◽  
Vol 22 (5) ◽  
Author(s):  
Marta F. Simões ◽  
Rui M. A. Pinto ◽  
Sérgio Simões
Keyword(s):  
Product Development ◽  
Hot Melt Extrusion ◽  
Melt Extrusion ◽  
Hot Melt

Continuous manufacturing of solid lipid nanoparticles by hot melt extrusion

2014 ◽  
Vol 471 (1-2) ◽  
pp. 153-156 ◽  
Author(s):  
Hemlata Patil ◽  
Vijay Kulkarni ◽  
Soumyajit Majumdar ◽  
Michael A. Repka
Keyword(s):  
Solid Lipid Nanoparticles ◽  
Hot Melt Extrusion ◽  
Lipid Nanoparticles ◽  
Continuous Manufacturing ◽  
Melt Extrusion ◽  
Solid Lipid ◽  
Hot Melt

scholarly journals Development and Validation of an in-line API Quantification Method Using AQbD Principles Based on UV-Vis Spectroscopy to Monitor and Optimise Continuous Hot Melt Extrusion Process

Pharmaceutics ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 150 ◽  
Author(s):  
Juan Almeida ◽  
Mariana Bezerra ◽  
Daniel Markl ◽  
Andreas Berghaus ◽  
Phil Borman ◽  
...  
Keyword(s):  
Quality By Design ◽  
Analytical Procedure ◽  
Design Principles ◽  
Hot Melt Extrusion ◽  
Extrusion Process ◽  
Melt Extrusion ◽  
Accuracy Profile ◽  
Vis Spectroscopy ◽  
Development And Validation ◽  
Hot Melt

A key principle of developing a new medicine is that quality should be built in, with a thorough understanding of the product and the manufacturing process supported by appropriate process controls. Quality by design principles that have been established for the development of drug products/substances can equally be applied to the development of analytical procedures. This paper presents the development and validation of a quantitative method to predict the concentration of piroxicam in Kollidon® VA 64 during hot melt extrusion using analytical quality by design principles. An analytical target profile was established for the piroxicam content and a novel in-line analytical procedure was developed using predictive models based on UV-Vis absorbance spectra collected during hot melt extrusion. Risks that impact the ability of the analytical procedure to measure piroxicam consistently were assessed using failure mode and effect analysis. The critical analytical attributes measured were colour (L* lightness, b* yellow to blue colour parameters—in-process critical quality attributes) that are linked to the ability to measure the API content and transmittance. The method validation was based on the accuracy profile strategy and ICH Q2(R1) validation criteria. The accuracy profile obtained with two validation sets showed that the 95% β-expectation tolerance limits for all piroxicam concentration levels analysed were within the combined trueness and precision acceptance limits set at ±5%. The method robustness was tested by evaluating the effects of screw speed (150–250 rpm) and feed rate (5–9 g/min) on piroxicam content around 15% w/w. In-line UV-Vis spectroscopy was shown to be a robust and practical PAT tool for monitoring the piroxicam content, a critical quality attribute in a pharmaceutical HME process.

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