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Impact of Hot-Melt Extrusion Processing Conditions on Physicochemical Properties of Amorphous Solid Dispersions Containing Thermally Labile Acrylic Copolymer.
J Pharm Sci. 2020 02; 109(2):1008-1019.JP

Abstract

For successful formulation of amorphous solid dispersions (ASDs) using hot-melt extrusion, it is imperative to understand the effect that heat and shear rate has on the physicochemical properties of the excipient. In this study, we investigated the influence of hot-melt extrusion parameters on solvent-free binary ASDs of ibuprofen (IBU), a model active pharmaceutical ingredient, in methacrylic acid-ethyl acrylate copolymer type A, 1:1, EUDRAGIT® L100-55 (EUD). To evaluate the impact of barrel temperature, screw speed, and residence time on EUD mass average molar mass and IBU release profile, size-exclusion chromatography and dissolution testing were used, respectively. The optimal conditions were established for IBU loadings less than 40 wt. %. For ASD formulations prepared using the ideal variables, spectral and thermal analyses confirmed that, under dry conditions at a temperature of 25°C, IBU remained amorphous during an 18-month storage period. After 28 months, formulations with active pharmaceutical ingredient content above 30 wt. % started to recrystallize. A temperature-composition phase diagram, constructed using melting point depression and glass-transition temperature measurements of IBU-EUD mixtures, correlated well with the long-term physical stability. The effect that minor-to-moderate polymer degradation within the extrudates has on their long-term physical stability and dissolution characteristics is analyzed and discussed.

Authors+Show Affiliations

Department of Physical Chemistry, University of Chemistry and Technology, Prague, Technická 5, 166 28 Prague 6, Czech Republic.Department of Chemical Engineering, University of Chemistry and Technology, Prague, Technická 3, 166 28 Prague 6, Czech Republic.Department of Polymers, University of Chemistry and Technology, Prague, Technická 3, 166 28 Prague 6, Czech Republic.Department of Polymers, University of Chemistry and Technology, Prague, Technická 3, 166 28 Prague 6, Czech Republic.Department of Physical Chemistry, University of Chemistry and Technology, Prague, Technická 5, 166 28 Prague 6, Czech Republic.Department of Physical Chemistry, University of Chemistry and Technology, Prague, Technická 5, 166 28 Prague 6, Czech Republic. Electronic address: fulemm@vscht.cz.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31605688

Citation

Mathers, Alex, et al. "Impact of Hot-Melt Extrusion Processing Conditions On Physicochemical Properties of Amorphous Solid Dispersions Containing Thermally Labile Acrylic Copolymer." Journal of Pharmaceutical Sciences, vol. 109, no. 2, 2020, pp. 1008-1019.
Mathers A, Hassouna F, Malinová L, et al. Impact of Hot-Melt Extrusion Processing Conditions on Physicochemical Properties of Amorphous Solid Dispersions Containing Thermally Labile Acrylic Copolymer. J Pharm Sci. 2020;109(2):1008-1019.
Mathers, A., Hassouna, F., Malinová, L., Merna, J., Růžička, K., & Fulem, M. (2020). Impact of Hot-Melt Extrusion Processing Conditions on Physicochemical Properties of Amorphous Solid Dispersions Containing Thermally Labile Acrylic Copolymer. Journal of Pharmaceutical Sciences, 109(2), 1008-1019. https://doi.org/10.1016/j.xphs.2019.10.005
Mathers A, et al. Impact of Hot-Melt Extrusion Processing Conditions On Physicochemical Properties of Amorphous Solid Dispersions Containing Thermally Labile Acrylic Copolymer. J Pharm Sci. 2020;109(2):1008-1019. PubMed PMID: 31605688.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Impact of Hot-Melt Extrusion Processing Conditions on Physicochemical Properties of Amorphous Solid Dispersions Containing Thermally Labile Acrylic Copolymer. AU - Mathers,Alex, AU - Hassouna,Fatima, AU - Malinová,Lenka, AU - Merna,Jan, AU - Růžička,Květoslav, AU - Fulem,Michal, Y1 - 2019/10/09/ PY - 2019/07/29/received PY - 2019/09/20/revised PY - 2019/10/01/accepted PY - 2019/10/13/pubmed PY - 2019/10/13/medline PY - 2019/10/13/entrez KW - amorphous solid dispersion(s) (ASD) KW - bioavailability KW - extrusion, polymer chemical, degradation KW - formulation KW - glass transition(s) KW - molecular weight KW - phase diagram(s) KW - physical stability KW - solubility SP - 1008 EP - 1019 JF - Journal of pharmaceutical sciences JO - J Pharm Sci VL - 109 IS - 2 N2 - For successful formulation of amorphous solid dispersions (ASDs) using hot-melt extrusion, it is imperative to understand the effect that heat and shear rate has on the physicochemical properties of the excipient. In this study, we investigated the influence of hot-melt extrusion parameters on solvent-free binary ASDs of ibuprofen (IBU), a model active pharmaceutical ingredient, in methacrylic acid-ethyl acrylate copolymer type A, 1:1, EUDRAGIT® L100-55 (EUD). To evaluate the impact of barrel temperature, screw speed, and residence time on EUD mass average molar mass and IBU release profile, size-exclusion chromatography and dissolution testing were used, respectively. The optimal conditions were established for IBU loadings less than 40 wt. %. For ASD formulations prepared using the ideal variables, spectral and thermal analyses confirmed that, under dry conditions at a temperature of 25°C, IBU remained amorphous during an 18-month storage period. After 28 months, formulations with active pharmaceutical ingredient content above 30 wt. % started to recrystallize. A temperature-composition phase diagram, constructed using melting point depression and glass-transition temperature measurements of IBU-EUD mixtures, correlated well with the long-term physical stability. The effect that minor-to-moderate polymer degradation within the extrudates has on their long-term physical stability and dissolution characteristics is analyzed and discussed. SN - 1520-6017 UR - https://www.unboundmedicine.com/medline/citation/31605688/Impact_of_Hot_Melt_Extrusion_Processing_Conditions_on_Physicochemical_Properties_of_Amorphous_Solid_Dispersions_Containing_Thermally_Labile_Acrylic_Copolymer_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-3549(19)30639-2 DB - PRIME DP - Unbound Medicine ER -