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Open AccessArticle

Co-crystals, Salts or Mixtures of Both? The Case of Tenofovir Alafenamide Fumarates

1
Sandoz GmbH, Early Stage Development, API Characterization, Biochemiestraße 10, AT-6250 Kundl, Austria
2
National Institute of Chemistry, Slovenian NMR Centre, Hajdrihova 19, SI-1001 Ljubljana, Slovenia
3
EN-FIST Centre of Excellence, Trg osvobodilne fronte 13, SI-1000 Ljubljana, Slovenia
4
Lek Pharmaceuticals d.d., Sandoz Development Center Slovenia, Verovškova ulica 57, SI-1526 Ljubljana, Slovenia
5
University of Ljubljana, Faculty of Chemistry and Chemical Technology, Večna pot 113, SI-1001 Ljubljana, Slovenia
6
Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, SI-1000 Ljubljana, Slovenia
*
Author to whom correspondence should be addressed.
Pharmaceutics 2020, 12(4), 342; https://doi.org/10.3390/pharmaceutics12040342
Received: 17 March 2020 / Revised: 3 April 2020 / Accepted: 7 April 2020 / Published: 10 April 2020
(This article belongs to the Special Issue Drug Polymorphism and Dosage Form Design)
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 15N-ssNMR (15N-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. View Full-Text
Keywords: co-crystal; salt; polymorphism; ssNMR; X-ray diffraction; tenofovir alafenamide fumarate co-crystal; salt; polymorphism; ssNMR; X-ray diffraction; tenofovir alafenamide fumarate
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MDPI and ACS Style

Lengauer, H.; Makuc, D.; Šterk, D.; Perdih, F.; Pichler, A.; Trdan Lušin, T.; Plavec, J.; Časar, Z. Co-crystals, Salts or Mixtures of Both? The Case of Tenofovir Alafenamide Fumarates. Pharmaceutics 2020, 12, 342.

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