Mechanical Activation by Ball Milling as a Strategy to Prepare Highly Soluble Pharmaceutical Formulations in the Form of Co-Amorphous, Co-Crystals, or Polymorphs
Almost half of orally administered active pharmaceutical ingredients (APIs) have low solubility, which affects their bioavailability. In the last two decades, several alternatives have been proposed to modify the crystalline structure of APIs to improve their solubility; these strategies consist of...
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MDPI AG
2022-09-01
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Online Access: | https://www.mdpi.com/1999-4923/14/10/2003 |
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author | Luz María Martínez Jorge Cruz-Angeles Mónica Vázquez-Dávila Eduardo Martínez Paulina Cabada Columba Navarrete-Bernal Flor Cortez |
author_facet | Luz María Martínez Jorge Cruz-Angeles Mónica Vázquez-Dávila Eduardo Martínez Paulina Cabada Columba Navarrete-Bernal Flor Cortez |
author_sort | Luz María Martínez |
collection | DOAJ |
description | Almost half of orally administered active pharmaceutical ingredients (APIs) have low solubility, which affects their bioavailability. In the last two decades, several alternatives have been proposed to modify the crystalline structure of APIs to improve their solubility; these strategies consist of inducing supramolecular structural changes in the active pharmaceutical ingredients, such as the amorphization and preparation of co-crystals or polymorphs. Since many APIs are thermosensitive, non-thermal emerging alternative techniques, such as mechanical activation by milling, have become increasingly common as a preparation method for drug formulations. This review summarizes the recent research in preparing pharmaceutical formulations (co-amorphous, co-crystals, and polymorphs) through ball milling to enhance the physicochemical properties of active pharmaceutical ingredients. This report includes detailed experimental milling conditions (instrumentation, temperature, time, solvent, etc.), as well as solubility, bioavailability, structural, and thermal stability data. The results and description of characterization techniques to determine the structural modifications resulting from transforming a pure crystalline API into a co-crystal, polymorph, or co-amorphous system are presented. Additionally, the characterization methodologies and results of intermolecular interactions induced by mechanical activation are discussed to explain the properties of the pharmaceutical formulations obtained after the ball milling process. |
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institution | Directory Open Access Journal |
issn | 1999-4923 |
language | English |
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publishDate | 2022-09-01 |
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series | Pharmaceutics |
spelling | doaj.art-ccbf8dfc3583441ba5c32bbbb8c18fd52023-11-24T01:53:33ZengMDPI AGPharmaceutics1999-49232022-09-011410200310.3390/pharmaceutics14102003Mechanical Activation by Ball Milling as a Strategy to Prepare Highly Soluble Pharmaceutical Formulations in the Form of Co-Amorphous, Co-Crystals, or PolymorphsLuz María Martínez0Jorge Cruz-Angeles1Mónica Vázquez-Dávila2Eduardo Martínez3Paulina Cabada4Columba Navarrete-Bernal5Flor Cortez6Tecnologico de Monterrey, School of Engineering and Sciences, Ave. Eugenio Garza Sada 2501 Sur, Monterrey 64849, NL, MexicoTecnologico de Monterrey, School of Engineering and Sciences, Ave. Eugenio Garza Sada 2501 Sur, Monterrey 64849, NL, MexicoTecnologico de Monterrey, School of Engineering and Sciences, Ave. Eugenio Garza Sada 2501 Sur, Monterrey 64849, NL, MexicoTecnologico de Monterrey, School of Engineering and Sciences, Ave. Eugenio Garza Sada 2501 Sur, Monterrey 64849, NL, MexicoTecnologico de Monterrey, School of Engineering and Sciences, Ave. Eugenio Garza Sada 2501 Sur, Monterrey 64849, NL, MexicoTecnologico de Monterrey, School of Engineering and Sciences, Ave. Eugenio Garza Sada 2501 Sur, Monterrey 64849, NL, MexicoTecnologico de Monterrey, School of Engineering and Sciences, Ave. Eugenio Garza Sada 2501 Sur, Monterrey 64849, NL, MexicoAlmost half of orally administered active pharmaceutical ingredients (APIs) have low solubility, which affects their bioavailability. In the last two decades, several alternatives have been proposed to modify the crystalline structure of APIs to improve their solubility; these strategies consist of inducing supramolecular structural changes in the active pharmaceutical ingredients, such as the amorphization and preparation of co-crystals or polymorphs. Since many APIs are thermosensitive, non-thermal emerging alternative techniques, such as mechanical activation by milling, have become increasingly common as a preparation method for drug formulations. This review summarizes the recent research in preparing pharmaceutical formulations (co-amorphous, co-crystals, and polymorphs) through ball milling to enhance the physicochemical properties of active pharmaceutical ingredients. This report includes detailed experimental milling conditions (instrumentation, temperature, time, solvent, etc.), as well as solubility, bioavailability, structural, and thermal stability data. The results and description of characterization techniques to determine the structural modifications resulting from transforming a pure crystalline API into a co-crystal, polymorph, or co-amorphous system are presented. Additionally, the characterization methodologies and results of intermolecular interactions induced by mechanical activation are discussed to explain the properties of the pharmaceutical formulations obtained after the ball milling process.https://www.mdpi.com/1999-4923/14/10/2003drugamorphousmillingco-crystalspolymorphsmechanical activation |
spellingShingle | Luz María Martínez Jorge Cruz-Angeles Mónica Vázquez-Dávila Eduardo Martínez Paulina Cabada Columba Navarrete-Bernal Flor Cortez Mechanical Activation by Ball Milling as a Strategy to Prepare Highly Soluble Pharmaceutical Formulations in the Form of Co-Amorphous, Co-Crystals, or Polymorphs Pharmaceutics drug amorphous milling co-crystals polymorphs mechanical activation |
title | Mechanical Activation by Ball Milling as a Strategy to Prepare Highly Soluble Pharmaceutical Formulations in the Form of Co-Amorphous, Co-Crystals, or Polymorphs |
title_full | Mechanical Activation by Ball Milling as a Strategy to Prepare Highly Soluble Pharmaceutical Formulations in the Form of Co-Amorphous, Co-Crystals, or Polymorphs |
title_fullStr | Mechanical Activation by Ball Milling as a Strategy to Prepare Highly Soluble Pharmaceutical Formulations in the Form of Co-Amorphous, Co-Crystals, or Polymorphs |
title_full_unstemmed | Mechanical Activation by Ball Milling as a Strategy to Prepare Highly Soluble Pharmaceutical Formulations in the Form of Co-Amorphous, Co-Crystals, or Polymorphs |
title_short | Mechanical Activation by Ball Milling as a Strategy to Prepare Highly Soluble Pharmaceutical Formulations in the Form of Co-Amorphous, Co-Crystals, or Polymorphs |
title_sort | mechanical activation by ball milling as a strategy to prepare highly soluble pharmaceutical formulations in the form of co amorphous co crystals or polymorphs |
topic | drug amorphous milling co-crystals polymorphs mechanical activation |
url | https://www.mdpi.com/1999-4923/14/10/2003 |
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