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Ball-Milling Preparation of the Drug–Drug Solid Form of Pioglitazone-Rosuvastatin at Different Molar Ratios: Characterization and Intrinsic Dissolution Rates Evaluation

Ball-milling using neat grinding (NG) or liquid-assisted grinding (LAG) by varying the polarity of the solvents allowed access to various drug–drug solid forms of pioglitazone hydrochloride (PGZ·HCl) and rosuvastatin calcium (RSV). Using NG, the coamorphous form was formed from the reaction of piogl...

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Autores principales: Muñoz Tecocoatzi, M. Fernanda, Páez-Franco, José C., Rubio-Carrasco, Kenneth, Núñez-Pineda, Alejandra, Dorazco-González, Alejandro, Fuentes-Noriega, Inés, Vilchis-Néstor, Alfredo R., Olvera, Lilian I., Morales-Morales, David, Germán-Acacio, Juan Manuel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9959797/
https://www.ncbi.nlm.nih.gov/pubmed/36839951
http://dx.doi.org/10.3390/pharmaceutics15020630
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author Muñoz Tecocoatzi, M. Fernanda
Páez-Franco, José C.
Rubio-Carrasco, Kenneth
Núñez-Pineda, Alejandra
Dorazco-González, Alejandro
Fuentes-Noriega, Inés
Vilchis-Néstor, Alfredo R.
Olvera, Lilian I.
Morales-Morales, David
Germán-Acacio, Juan Manuel
author_facet Muñoz Tecocoatzi, M. Fernanda
Páez-Franco, José C.
Rubio-Carrasco, Kenneth
Núñez-Pineda, Alejandra
Dorazco-González, Alejandro
Fuentes-Noriega, Inés
Vilchis-Néstor, Alfredo R.
Olvera, Lilian I.
Morales-Morales, David
Germán-Acacio, Juan Manuel
author_sort Muñoz Tecocoatzi, M. Fernanda
collection PubMed
description Ball-milling using neat grinding (NG) or liquid-assisted grinding (LAG) by varying the polarity of the solvents allowed access to various drug–drug solid forms of pioglitazone hydrochloride (PGZ·HCl) and rosuvastatin calcium (RSV). Using NG, the coamorphous form was formed from the reaction of pioglitazone hydrochloride (PGZ·HCl) and rosuvastatin calcium (RSV) in a 2:1 molar ratio. The formation of the expected coamorphous salt could not be corroborated by FT-IR, but DSC data showed that it was indeed a single-phase amorphous mixture. By varying the molar ratios of the reactants, either keeping PGZ·HCl constant and varying RSV or vice versa, another coamorphous form was obtained when a 1:1 molar ratio was employed. In the case of the other outcomes, it was observed that they were a mixture of solid forms coexisting simultaneously with the coamorphous forms (1:1 or 2:1) together with the drug that was in excess. When RSV was in excess, it was in an amorphous form. In the case of PGZ·HCl, it was found in a semicrystalline form. The intrinsic dissolution rates (IDRs) of the solid forms of PGZ·HCl-RSV in stoichiometric ratios (1:1, 2:1, 1:4, 6:1, and 1:10) were evaluated. Interestingly, a synchronized release of both drugs in the dissolution medium was observed. In the case of the release of RSV, there were no improvements in the dissolution profiles, because the acidic media caused the formation of degradation products, limiting any probable modification in the dissolution processes. However, the coamorphous 2:1 form exhibited an improvement of 1.03 times with respect to pure PGZ·HCl. It is proposed that the modification of the dissolution process of the coamorphous 2:1 form was limited by changes in the pH of the media as RSV consumes protons from the media due to degradation processes.
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spelling pubmed-99597972023-02-26 Ball-Milling Preparation of the Drug–Drug Solid Form of Pioglitazone-Rosuvastatin at Different Molar Ratios: Characterization and Intrinsic Dissolution Rates Evaluation Muñoz Tecocoatzi, M. Fernanda Páez-Franco, José C. Rubio-Carrasco, Kenneth Núñez-Pineda, Alejandra Dorazco-González, Alejandro Fuentes-Noriega, Inés Vilchis-Néstor, Alfredo R. Olvera, Lilian I. Morales-Morales, David Germán-Acacio, Juan Manuel Pharmaceutics Article Ball-milling using neat grinding (NG) or liquid-assisted grinding (LAG) by varying the polarity of the solvents allowed access to various drug–drug solid forms of pioglitazone hydrochloride (PGZ·HCl) and rosuvastatin calcium (RSV). Using NG, the coamorphous form was formed from the reaction of pioglitazone hydrochloride (PGZ·HCl) and rosuvastatin calcium (RSV) in a 2:1 molar ratio. The formation of the expected coamorphous salt could not be corroborated by FT-IR, but DSC data showed that it was indeed a single-phase amorphous mixture. By varying the molar ratios of the reactants, either keeping PGZ·HCl constant and varying RSV or vice versa, another coamorphous form was obtained when a 1:1 molar ratio was employed. In the case of the other outcomes, it was observed that they were a mixture of solid forms coexisting simultaneously with the coamorphous forms (1:1 or 2:1) together with the drug that was in excess. When RSV was in excess, it was in an amorphous form. In the case of PGZ·HCl, it was found in a semicrystalline form. The intrinsic dissolution rates (IDRs) of the solid forms of PGZ·HCl-RSV in stoichiometric ratios (1:1, 2:1, 1:4, 6:1, and 1:10) were evaluated. Interestingly, a synchronized release of both drugs in the dissolution medium was observed. In the case of the release of RSV, there were no improvements in the dissolution profiles, because the acidic media caused the formation of degradation products, limiting any probable modification in the dissolution processes. However, the coamorphous 2:1 form exhibited an improvement of 1.03 times with respect to pure PGZ·HCl. It is proposed that the modification of the dissolution process of the coamorphous 2:1 form was limited by changes in the pH of the media as RSV consumes protons from the media due to degradation processes. MDPI 2023-02-13 /pmc/articles/PMC9959797/ /pubmed/36839951 http://dx.doi.org/10.3390/pharmaceutics15020630 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Muñoz Tecocoatzi, M. Fernanda
Páez-Franco, José C.
Rubio-Carrasco, Kenneth
Núñez-Pineda, Alejandra
Dorazco-González, Alejandro
Fuentes-Noriega, Inés
Vilchis-Néstor, Alfredo R.
Olvera, Lilian I.
Morales-Morales, David
Germán-Acacio, Juan Manuel
Ball-Milling Preparation of the Drug–Drug Solid Form of Pioglitazone-Rosuvastatin at Different Molar Ratios: Characterization and Intrinsic Dissolution Rates Evaluation
title Ball-Milling Preparation of the Drug–Drug Solid Form of Pioglitazone-Rosuvastatin at Different Molar Ratios: Characterization and Intrinsic Dissolution Rates Evaluation
title_full Ball-Milling Preparation of the Drug–Drug Solid Form of Pioglitazone-Rosuvastatin at Different Molar Ratios: Characterization and Intrinsic Dissolution Rates Evaluation
title_fullStr Ball-Milling Preparation of the Drug–Drug Solid Form of Pioglitazone-Rosuvastatin at Different Molar Ratios: Characterization and Intrinsic Dissolution Rates Evaluation
title_full_unstemmed Ball-Milling Preparation of the Drug–Drug Solid Form of Pioglitazone-Rosuvastatin at Different Molar Ratios: Characterization and Intrinsic Dissolution Rates Evaluation
title_short Ball-Milling Preparation of the Drug–Drug Solid Form of Pioglitazone-Rosuvastatin at Different Molar Ratios: Characterization and Intrinsic Dissolution Rates Evaluation
title_sort ball-milling preparation of the drug–drug solid form of pioglitazone-rosuvastatin at different molar ratios: characterization and intrinsic dissolution rates evaluation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9959797/
https://www.ncbi.nlm.nih.gov/pubmed/36839951
http://dx.doi.org/10.3390/pharmaceutics15020630
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