Virtual Cocrystal Screening of Adefovir Dipivoxyl: Identification of New Solid Forms with Improved Dissolution and Permeation Profiles
The application of a computational screening methodology based on the calculation of intermolecular interaction energies has guided the discovery of new multicomponent solid forms of the oral antiviral Adefovir Dipivoxyl. Three new cocrystals with resorcinol, orcinol and hydroquinone have been synth...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/11/2310 |
| _version_ | 1797466840526487552 |
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| author | Rafael Barbas Hanan Fael Samuel Lee Rebeca Ruiz Christopher A. Hunter Elisabet Fuguet Clara Ràfols Rafel Prohens |
| author_facet | Rafael Barbas Hanan Fael Samuel Lee Rebeca Ruiz Christopher A. Hunter Elisabet Fuguet Clara Ràfols Rafel Prohens |
| author_sort | Rafael Barbas |
| collection | DOAJ |
| description | The application of a computational screening methodology based on the calculation of intermolecular interaction energies has guided the discovery of new multicomponent solid forms of the oral antiviral Adefovir Dipivoxyl. Three new cocrystals with resorcinol, orcinol and hydroquinone have been synthesized and thoroughly characterized. They show improved dissolution profiles with respect to the single solid form, particularly the cocrystals of orcinol and resorcinol, which have 3.2- and 2-fold faster dissolution rates at stomach conditions (pH 1.5). Moreover, dynamic dissolution experiments that simultaneously mimic both the pH variation along the gastrointestinal tract and the partition into biological membranes show that, in addition to the faster initial dissolution, Adefovir Dipivoxyl also penetrates faster into the organic membranes in the form of resorcinol and orcinol cocrystals. |
| first_indexed | 2024-03-09T18:45:23Z |
| format | Article |
| id | doaj.art-c01151c7f62f4c8da8774c40da48264b |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T18:45:23Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-c01151c7f62f4c8da8774c40da48264b2023-11-24T06:20:09ZengMDPI AGPharmaceutics1999-49232022-10-011411231010.3390/pharmaceutics14112310Virtual Cocrystal Screening of Adefovir Dipivoxyl: Identification of New Solid Forms with Improved Dissolution and Permeation ProfilesRafael Barbas0Hanan Fael1Samuel Lee2Rebeca Ruiz3Christopher A. Hunter4Elisabet Fuguet5Clara Ràfols6Rafel Prohens7Unitat de Polimorfisme i Calorimetria, Centres Científics i Tecnològics, Universitat de Barcelona, Baldiri Reixac 10, 08028 Barcelona, SpainDepartament d’Enginyeria Química i Química Analítica, Universitat de Barcelona, Martí i Franquès 1-11, 08028 Barcelona, SpainPion Inc., Forest Row Business Park, Forest Row, East Sussex RH18 5DW, UKPion Inc., Forest Row Business Park, Forest Row, East Sussex RH18 5DW, UKYusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UKDepartament d’Enginyeria Química i Química Analítica, Universitat de Barcelona, Martí i Franquès 1-11, 08028 Barcelona, SpainDepartament d’Enginyeria Química i Química Analítica, Universitat de Barcelona, Martí i Franquès 1-11, 08028 Barcelona, SpainUnitat de Polimorfisme i Calorimetria, Centres Científics i Tecnològics, Universitat de Barcelona, Baldiri Reixac 10, 08028 Barcelona, SpainThe application of a computational screening methodology based on the calculation of intermolecular interaction energies has guided the discovery of new multicomponent solid forms of the oral antiviral Adefovir Dipivoxyl. Three new cocrystals with resorcinol, orcinol and hydroquinone have been synthesized and thoroughly characterized. They show improved dissolution profiles with respect to the single solid form, particularly the cocrystals of orcinol and resorcinol, which have 3.2- and 2-fold faster dissolution rates at stomach conditions (pH 1.5). Moreover, dynamic dissolution experiments that simultaneously mimic both the pH variation along the gastrointestinal tract and the partition into biological membranes show that, in addition to the faster initial dissolution, Adefovir Dipivoxyl also penetrates faster into the organic membranes in the form of resorcinol and orcinol cocrystals.https://www.mdpi.com/1999-4923/14/11/2310Adefovir Dipivoxylpolyphenolscocrystalcocrystallizationcomputational screeningdissolution rate |
| spellingShingle | Rafael Barbas Hanan Fael Samuel Lee Rebeca Ruiz Christopher A. Hunter Elisabet Fuguet Clara Ràfols Rafel Prohens Virtual Cocrystal Screening of Adefovir Dipivoxyl: Identification of New Solid Forms with Improved Dissolution and Permeation Profiles Pharmaceutics Adefovir Dipivoxyl polyphenols cocrystal cocrystallization computational screening dissolution rate |
| title | Virtual Cocrystal Screening of Adefovir Dipivoxyl: Identification of New Solid Forms with Improved Dissolution and Permeation Profiles |
| title_full | Virtual Cocrystal Screening of Adefovir Dipivoxyl: Identification of New Solid Forms with Improved Dissolution and Permeation Profiles |
| title_fullStr | Virtual Cocrystal Screening of Adefovir Dipivoxyl: Identification of New Solid Forms with Improved Dissolution and Permeation Profiles |
| title_full_unstemmed | Virtual Cocrystal Screening of Adefovir Dipivoxyl: Identification of New Solid Forms with Improved Dissolution and Permeation Profiles |
| title_short | Virtual Cocrystal Screening of Adefovir Dipivoxyl: Identification of New Solid Forms with Improved Dissolution and Permeation Profiles |
| title_sort | virtual cocrystal screening of adefovir dipivoxyl identification of new solid forms with improved dissolution and permeation profiles |
| topic | Adefovir Dipivoxyl polyphenols cocrystal cocrystallization computational screening dissolution rate |
| url | https://www.mdpi.com/1999-4923/14/11/2310 |
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