Co-Crystals of the Anti-HIV Drugs Lamivudine and Zidovudine

Abstract

Co-crystal forming abilities of the two anti-HIV drugs lamivudine and zidovudine were studied. A study of five crystal structures was carried out to investigate the general applicability of the retrosynthetic approach in the design of new co-crystals. This analysis of co-crystals and salt structures showed a complete to partial success, and in one case, a total failure to obtain the predicted synthon. Both screening strategies and retrosynthetic methods may be appropriate for the discovery of new active pharmaceutical ingredients co-crystals.

Quasi-enantiomeric single-nucleoside and quasi-racemic two-nucleoside hydrochloride salts and ruthenium complexes of cytidine and 2′,3′-dideoxycytidine analogs unveiling the negligible structure-driving role of the 2′,3′-moieties

“…6 In this sense, multicomponent molecular crystals of active pharmaceutical ingredients (APIs) are widely investigated due to the welcome possibility of manipulating a functional and/or technical feature in association with practical preparation procedures chemically designed without serendipity, higher yield, reproducibility, and purity. 7 Lamivudine (β-L-2′,3′-dideoxy-3′-thiacytidine, 3TC) is an API of the nucleoside reverse transcriptase inhibitor (NRTI) class used against both AIDS (HIV) and hepatitis B (HBV) viruses. It was originally marketed by the pharmaceutical company GlaxoSmithKline under the brand name EPIVIR®.…”

Pharmaceutical Cocrystals: An Overview

“…During dissolution, the functional groups in the drug and conformer interact with each other and form hydrogen bonds [89] . This is most commonly used method for the preparation of cocrystals by researchers [79,94] .…”

Crystal Forms of Anti-HIV Drugs: Role of Recrystallization

“…The cocrystals of efavirenz with 4,4'-bipyridyl and 1,4-cyclohexanedione prepared by recrystallization of their grounded mixture from THF and from a mixture of n-heptane and THF respectively have been reported by Mahapatra et al (Mahapatra et al, 2010). Similarly, the multiple hydrogen bond donor and acceptor groups of lamivudine and zidovudine have been utilized by Bhatt et al for designing their cocrystals (Bhatt et al, 2009). These authors have designed zidovudine cocrystal using retrosynthetic approach where two drug molecules and one molecule of 2,4,6-triaminopyrimidine are held together by a three point synthon which forms basic part of their cocrystal structure (Figure 10).…”