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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Main Authors: Luz María Martínez, Jorge Cruz-Angeles, Mónica Vázquez-Dávila, Eduardo Martínez, Paulina Cabada, Columba Navarrete-Bernal, Flor Cortez
Format: Article
Language:English
Published: MDPI AG 2022-09-01
Series:Pharmaceutics
Subjects:
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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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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