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Rivaroxaban polymeric amorphous solid dispersions: Moisture-induced thermodynamic phase behavior and intermolecular interactions.
Eur J Pharm Biopharm. 2019 Dec; 145:98-112.EJ

Abstract

The present study evaluates the physical stability and intermolecular interactions of Rivaroxaban (RXB) amorphous solid dispersions (ASDs) in polymeric carriers via thermodynamic modelling and molecular simulations. Specifically, the Flory-Huggins (FH) lattice solution theory was used to construct thermodynamic phase diagrams of RXB ASDs in four commonly used polymeric carriers (i.e. copovidone, coPVP, povidone, PVP, Soluplus, SOL and hypromellose acetate succinate, HPMCAS), which were stored under 0%, 60% and 75% relative humidity (RH) conditions. In order to verify the phase boundaries predicted by FH modelling (i.e. truly amorphous zone, amorphous-amorphous demixing zones and amorphous-API recrystallization zones), samples of ASDs were examined via polarized light microscopy after storage for up to six months at various RH conditions. Results showed a good agreement between the theoretical and the experimental approaches (i.e. coPVP and PVP resulted in less physically-stable ASDs compared to SOL and HPMCAS) indicating that the proposed FH-based modelling may be a useful tool in predicting long-term physical stability in high humidity conditions. In addition, molecular dynamics (MD) simulations were employed in order to interpret the observed differences in physical stability. Results, which were verified via differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR), suggested the formation of similar intermolecular interactions in all cases, indicating that the interaction with moisture water plays a more crucial role in ASD physical stability compared to the formation of intermolecular interactions between ASD components.

Authors+Show Affiliations

Department of Pharmaceutical Technology, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.Department of Pharmaceutical Technology, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.Department of Pharmaceutical Technology, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.Department of Pharmaceutical Technology, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.Department of Pharmaceutical Technology, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece. Electronic address: pbarmp@pharm.auth.gr.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31698042

Citation

Kapourani, Afroditi, et al. "Rivaroxaban Polymeric Amorphous Solid Dispersions: Moisture-induced Thermodynamic Phase Behavior and Intermolecular Interactions." European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, vol. 145, 2019, pp. 98-112.
Kapourani A, Vardaka E, Katopodis K, et al. Rivaroxaban polymeric amorphous solid dispersions: Moisture-induced thermodynamic phase behavior and intermolecular interactions. Eur J Pharm Biopharm. 2019;145:98-112.
Kapourani, A., Vardaka, E., Katopodis, K., Kachrimanis, K., & Barmpalexis, P. (2019). Rivaroxaban polymeric amorphous solid dispersions: Moisture-induced thermodynamic phase behavior and intermolecular interactions. European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, 145, 98-112. https://doi.org/10.1016/j.ejpb.2019.10.010
Kapourani A, et al. Rivaroxaban Polymeric Amorphous Solid Dispersions: Moisture-induced Thermodynamic Phase Behavior and Intermolecular Interactions. Eur J Pharm Biopharm. 2019;145:98-112. PubMed PMID: 31698042.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rivaroxaban polymeric amorphous solid dispersions: Moisture-induced thermodynamic phase behavior and intermolecular interactions. AU - Kapourani,Afroditi, AU - Vardaka,Elisavet, AU - Katopodis,Konstantinos, AU - Kachrimanis,Kyriakos, AU - Barmpalexis,Panagiotis, Y1 - 2019/11/04/ PY - 2019/08/20/received PY - 2019/10/19/revised PY - 2019/10/22/accepted PY - 2019/11/8/pubmed PY - 2019/11/27/medline PY - 2019/11/8/entrez KW - Amorphous solid dispersions KW - Flory-Huggins lattice theory KW - Molecular dynamics simulations KW - RH-phase diagrams KW - Rivaroxaban KW - Thermodynamic modelling SP - 98 EP - 112 JF - European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V JO - Eur J Pharm Biopharm VL - 145 N2 - The present study evaluates the physical stability and intermolecular interactions of Rivaroxaban (RXB) amorphous solid dispersions (ASDs) in polymeric carriers via thermodynamic modelling and molecular simulations. Specifically, the Flory-Huggins (FH) lattice solution theory was used to construct thermodynamic phase diagrams of RXB ASDs in four commonly used polymeric carriers (i.e. copovidone, coPVP, povidone, PVP, Soluplus, SOL and hypromellose acetate succinate, HPMCAS), which were stored under 0%, 60% and 75% relative humidity (RH) conditions. In order to verify the phase boundaries predicted by FH modelling (i.e. truly amorphous zone, amorphous-amorphous demixing zones and amorphous-API recrystallization zones), samples of ASDs were examined via polarized light microscopy after storage for up to six months at various RH conditions. Results showed a good agreement between the theoretical and the experimental approaches (i.e. coPVP and PVP resulted in less physically-stable ASDs compared to SOL and HPMCAS) indicating that the proposed FH-based modelling may be a useful tool in predicting long-term physical stability in high humidity conditions. In addition, molecular dynamics (MD) simulations were employed in order to interpret the observed differences in physical stability. Results, which were verified via differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR), suggested the formation of similar intermolecular interactions in all cases, indicating that the interaction with moisture water plays a more crucial role in ASD physical stability compared to the formation of intermolecular interactions between ASD components. SN - 1873-3441 UR - https://www.unboundmedicine.com/medline/citation/31698042/Rivaroxaban_polymeric_amorphous_solid_dispersions:_Moisture_induced_thermodynamic_phase_behavior_and_intermolecular_interactions_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0939-6411(19)31289-5 DB - PRIME DP - Unbound Medicine ER -