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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; 10(4)P

Abstract

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.

Authors+Show Affiliations

Leicester School of Pharmacy, De Montfort University, Leicester LE1 9BH, UK. wss@dmu.ac.uk.Leicester School of Pharmacy, De Montfort University, Leicester LE1 9BH, UK. mariana.bezerra@dmu.ac.uk.Leicester School of Pharmacy, De Montfort University, Leicester LE1 9BH, UK. juan.zelayaalmeida@dmu.ac.uk.ColVisTec AG, 12489 Berlin, Germany. a.berghaus@colvistec.de.Insight by Design Ltd., Stevenage SG9 9ST, UK. martin.owen.insight@gmail.com.GMPharma Ltd., Stevenage SG2 8SB, UK. gordon.muirhead@gmpharma.co.uk.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30249025

Citation

Schlindwein, Walkiria, et al. "In-Line UV-Vis Spectroscopy as a Fast-Working Process Analytical Technology (PAT) During Early Phase Product Development Using Hot Melt Extrusion (HME)." Pharmaceutics, vol. 10, no. 4, 2018.
Schlindwein W, Bezerra M, Almeida J, et al. 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;10(4).
Schlindwein, W., Bezerra, M., Almeida, J., Berghaus, A., Owen, M., & Muirhead, G. (2018). In-Line UV-Vis Spectroscopy as a Fast-Working Process Analytical Technology (PAT) during Early Phase Product Development Using Hot Melt Extrusion (HME). Pharmaceutics, 10(4), doi:10.3390/pharmaceutics10040166.
Schlindwein W, et al. 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 Sep 23;10(4) PubMed PMID: 30249025.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In-Line UV-Vis Spectroscopy as a Fast-Working Process Analytical Technology (PAT) during Early Phase Product Development Using Hot Melt Extrusion (HME). AU - Schlindwein,Walkiria, AU - Bezerra,Mariana, AU - Almeida,Juan, AU - Berghaus,Andreas, AU - Owen,Martin, AU - Muirhead,Gordon, Y1 - 2018/09/23/ PY - 2018/05/21/received PY - 2018/09/04/revised PY - 2018/09/11/accepted PY - 2018/9/26/entrez PY - 2018/9/27/pubmed PY - 2018/9/27/medline KW - Kollidon® VA64 KW - Process Analytical Technology (PAT) KW - Quality by Design KW - continuous manufacturing KW - hot melt extrusion (HME) KW - in-line UV-Vis spectroscopy KW - piroxicam JF - Pharmaceutics JO - Pharmaceutics VL - 10 IS - 4 N2 - 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. SN - 1999-4923 UR - https://www.unboundmedicine.com/medline/citation/30249025/In_Line_UV_Vis_Spectroscopy_as_a_Fast_Working_Process_Analytical_Technology__PAT__during_Early_Phase_Product_Development_Using_Hot_Melt_Extrusion__HME__ L2 - http://www.mdpi.com/resolver?pii=pharmaceutics10040166 DB - PRIME DP - Unbound Medicine ER -