Co-crystals, Salts or Mixtures of Both? The Case of Tenofovir Alafenamide Fumarates
Tenofovir alafenamide fumarate (TAF) is the newest prodrug of tenofovir that constitutes several drug products used for the treatment of HIV/AIDS. Although the solid-state properties of its predecessor tenofovir disoproxil fumarate have been investigated and described in the literature, there are no...
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| Format: | Article |
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MDPI AG
2020-04-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/12/4/342 |
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| author | Hannes Lengauer Damjan Makuc Damjan Šterk Franc Perdih Arthur Pichler Tina Trdan Lušin Janez Plavec Zdenko Časar |
| author_facet | Hannes Lengauer Damjan Makuc Damjan Šterk Franc Perdih Arthur Pichler Tina Trdan Lušin Janez Plavec Zdenko Časar |
| author_sort | Hannes Lengauer |
| collection | DOAJ |
| description | Tenofovir alafenamide fumarate (TAF) is the newest prodrug of tenofovir that constitutes several drug products used for the treatment of HIV/AIDS. Although the solid-state properties of its predecessor tenofovir disoproxil fumarate have been investigated and described in the literature, there are no data in the scientific literature on the solid state properties of TAF. In our report, we describe the preparation of two novel polymorphs II and III of tenofovir alafenamide monofumarate (TA MF2 and TA MF3). The solid-state structure of these compounds was investigated in parallel to the previously known tenofovir alafenamide monofumarate form I (TA MF1) and tenofovir alafenamide hemifumarate (TA HF). Interestingly, the single-crystal X-ray diffraction of TA HF revealed that this derivative exists as a co-crystal form. In addition, we prepared a crystalline tenofovir alafenamide free base (TA) and its hydrochloride salt (TA HCl), which enabled us to determine the structure of TA MF derivatives using <sup>15</sup>N-ssNMR (<sup>15</sup>N-solid state nuclear magnetic resonance). Surprisingly, we observed that TA MF1 exists as a mixed ionization state complex or pure salt, while TA MF2 and TA MF3 can be obtained as pure co-crystal forms. |
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| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T20:32:04Z |
| publishDate | 2020-04-01 |
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| series | Pharmaceutics |
| spelling | doaj.art-9165c6196f6740e89e97d5328de7b0fe2023-11-19T21:17:52ZengMDPI AGPharmaceutics1999-49232020-04-0112434210.3390/pharmaceutics12040342Co-crystals, Salts or Mixtures of Both? The Case of Tenofovir Alafenamide FumaratesHannes Lengauer0Damjan Makuc1Damjan Šterk2Franc Perdih3Arthur Pichler4Tina Trdan Lušin5Janez Plavec6Zdenko Časar7Sandoz GmbH, Early Stage Development, API Characterization, Biochemiestraße 10, AT-6250 Kundl, AustriaNational Institute of Chemistry, Slovenian NMR Centre, Hajdrihova 19, SI-1001 Ljubljana, SloveniaLek Pharmaceuticals d.d., Sandoz Development Center Slovenia, Verovškova ulica 57, SI-1526 Ljubljana, SloveniaUniversity of Ljubljana, Faculty of Chemistry and Chemical Technology, Večna pot 113, SI-1001 Ljubljana, SloveniaSandoz GmbH, Early Stage Development, API Characterization, Biochemiestraße 10, AT-6250 Kundl, AustriaLek Pharmaceuticals d.d., Sandoz Development Center Slovenia, Verovškova ulica 57, SI-1526 Ljubljana, SloveniaNational Institute of Chemistry, Slovenian NMR Centre, Hajdrihova 19, SI-1001 Ljubljana, SloveniaLek Pharmaceuticals d.d., Sandoz Development Center Slovenia, Verovškova ulica 57, SI-1526 Ljubljana, SloveniaTenofovir alafenamide fumarate (TAF) is the newest prodrug of tenofovir that constitutes several drug products used for the treatment of HIV/AIDS. Although the solid-state properties of its predecessor tenofovir disoproxil fumarate have been investigated and described in the literature, there are no data in the scientific literature on the solid state properties of TAF. In our report, we describe the preparation of two novel polymorphs II and III of tenofovir alafenamide monofumarate (TA MF2 and TA MF3). The solid-state structure of these compounds was investigated in parallel to the previously known tenofovir alafenamide monofumarate form I (TA MF1) and tenofovir alafenamide hemifumarate (TA HF). Interestingly, the single-crystal X-ray diffraction of TA HF revealed that this derivative exists as a co-crystal form. In addition, we prepared a crystalline tenofovir alafenamide free base (TA) and its hydrochloride salt (TA HCl), which enabled us to determine the structure of TA MF derivatives using <sup>15</sup>N-ssNMR (<sup>15</sup>N-solid state nuclear magnetic resonance). Surprisingly, we observed that TA MF1 exists as a mixed ionization state complex or pure salt, while TA MF2 and TA MF3 can be obtained as pure co-crystal forms.https://www.mdpi.com/1999-4923/12/4/342co-crystalsaltpolymorphismssNMRX-ray diffractiontenofovir alafenamide fumarate |
| spellingShingle | Hannes Lengauer Damjan Makuc Damjan Šterk Franc Perdih Arthur Pichler Tina Trdan Lušin Janez Plavec Zdenko Časar Co-crystals, Salts or Mixtures of Both? The Case of Tenofovir Alafenamide Fumarates Pharmaceutics co-crystal salt polymorphism ssNMR X-ray diffraction tenofovir alafenamide fumarate |
| title | Co-crystals, Salts or Mixtures of Both? The Case of Tenofovir Alafenamide Fumarates |
| title_full | Co-crystals, Salts or Mixtures of Both? The Case of Tenofovir Alafenamide Fumarates |
| title_fullStr | Co-crystals, Salts or Mixtures of Both? The Case of Tenofovir Alafenamide Fumarates |
| title_full_unstemmed | Co-crystals, Salts or Mixtures of Both? The Case of Tenofovir Alafenamide Fumarates |
| title_short | Co-crystals, Salts or Mixtures of Both? The Case of Tenofovir Alafenamide Fumarates |
| title_sort | co crystals salts or mixtures of both the case of tenofovir alafenamide fumarates |
| topic | co-crystal salt polymorphism ssNMR X-ray diffraction tenofovir alafenamide fumarate |
| url | https://www.mdpi.com/1999-4923/12/4/342 |
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