Co-crystals, salts or mixtures of both? The case of tenofovir alafenamide fumarates

Lengauer, Hannes (author), Makuc, Damjan (author), Šterk, Damjan (author), Perdih, Franc (author), Pichler, Arthur (author), Trdan Lušin, Tina (author), Plavec, Janez (author), Časar, Zdenko (author)

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 $^{15}$N-ssNMR ($^{15}$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.

• Language: English
• Keywords: co-crystal, salt, polymorphism, X-ray diffraction, ssNMR, tenofovir alafenamide fumarate
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FKKT - Faculty of Chemistry and Chemical Technology; FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2020
• Number of pages: 21 str.
• Numbering: Vol. 12, iss. 4, art. 342
• PID: 20.500.12556/RUL-133367
• UDC: 615
• ISSN on article: 1999-4923
• DOI: 10.3390/pharmaceutics12040342
• COBISS.SI-ID: 1569374
• Publication date in RUL: 24.11.2021

Record is a part of a journal

• Title: Pharmaceutics
• Shortened title: Pharmaceutics
• Publisher: MDPI
• ISSN: 1999-4923
• COBISS.SI-ID: 517949977

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• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 10.04.2020

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• Funder: Other - Other funder or multiple funders
• Funding programme: Lek/Sandoz