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

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

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.

• Jezik: Angleški jezik
• Ključne besede: co-crystal, salt, polymorphism, X-ray diffraction, ssNMR, tenofovir alafenamide fumarate
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FKKT - Fakulteta za kemijo in kemijsko tehnologijo ; FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2020
• Št. strani: 21 str.
• Številčenje: Vol. 12, iss. 4, art. 342
• PID: 20.500.12556/RUL-133367
• UDK: 615
• ISSN pri članku: 1999-4923
• DOI: 10.3390/pharmaceutics12040342
• COBISS.SI-ID: 1569374
• Datum objave v RUL: 24.11.2021

Gradivo je del revije

• Naslov: Pharmaceutics
• Skrajšan naslov: Pharmaceutics
• Založnik: MDPI
• ISSN: 1999-4923
• COBISS.SI-ID: 517949977

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
• Začetek licenciranja: 10.04.2020

Projekti

• Financer: Drugi - Drug financer ali več financerjev
• Program financ.: Lek/Sandoz