Lamivudine hemihydrate

Abstract

A new lamivudine hydrate, namely, cis-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)pyrimidin-2(1H)-one hemihydrate, C(8)H(11)N(3)O(3)S.0.5H(2)O, has been synthesized and structurally characterized by both powder and single-crystal X-ray diffraction studies. The hemihydrate crystallizes in the Sohnke space group P2(1), with the asymmetric unit comprising four lamivudine and two water molecules. An extensive network of intermolecular hydrogen bonds involving both lamivudine and solvent water molecules generates a three-dimensional supramolecular architecture. The structural data and crystal packing of the present lamivudine hemihydrate are compared with those of other hydrated and anhydrous forms of lamivudine.

Isostructurality and the conformational role of the 2′,3′-moieties in the diversity of lamivudine crystal forms probed in halide salts

“…2b). There is also a relatively close distance between the S3′ and the centroid calculated between these two cytosinium atoms, namely, 3.378(8) Å in the hydrochloride salt and 3.362 (6) Å in the hydrobromide one.…”

“…Crystal engineering of the anti-HIV drug lamivudine has currently provided improvement in its pharmaceutical performance besides getting insights into several branches of nucleoside structural chemistry. [1][2][3][4][5][6][7][8][9][10][11][12][13] Targeting pharmaceutical improvements, the design of crystal structures has produced some salts of active pharmaceutical ingredients showing important improvement in its solubility and purity. 11,14 Furthermore, the ability of nucleosides to assemble base-stacked and base-paired double-stranded helices even without phosphodiester linkages in crystals was demonstrated in three structures of the drug similar to DNA duplexes.…”

Lamivudine Salts with Improved Solubilities

“…In fact, lamivudine can be considered a “promiscuous” drug in terms of the crystallization phenomenon fidelity. This API has a remarkable capability to crystallize in different solid‐state phases 26–32. At least eleven crystal phases are reported for lamivudine: (1) form I, a 0.2 hydrate30; (2) form II, an anhydrous polymorph30; (3) form III, a hemihydrate31; (4) a saccharinate salt26; (5) a maleate salt27; (6) a 3,5‐dinitrosalicylate salt hydrate with 2:1:1 lamivudine–3,5‐dinitrosalicylic acid–H 2 O stoichiometry28; (7) a 4‐quinolinone cocrystal28; (8) a hydrated zidovudine cocrystal with 1:1:1 lamivudine–zidovudine–H 2 O stoichiometry28; (9) a lamivudine duplex with 8:2:2:1:4 lamivudine–maleic acid–HCl–(CH 3 ) 2 CHOH–H 2 O stoichiometry29; (10) a hydrochloride salt anhydrate32; and (11) a hydrochloride salt monohydrate 32.…”

Lamivudine salts with 1,2-dicarboxylic acids: A new and a rare synthon with double pairing motif fine-tuning their solubility

“…[3][4][5][6][7][8][9][10][11] So far, at least fourteen different crystalline structures of lamivudine have been reported: (1) form I, a 0.2 hydrate; 3 (2) form II, an anhydrous polymorh; 3 (3) a saccharinate salt; 4 (4) a 3,5-dinitrosalicylate salt hydrate; 5 (5) a 4-quinolinone cocrystal; 5 (6) a zidovudine cocrystal hydrate; 5 (7) a hydrogen maleate salt; 6 (8) lamivudine duplexes I 7 and (9) II; 8 (10) form III, a hemihydrate; 9 (11) a hydrochloride salt anhydrate 10 and (12) a hydrochloride salt monohydrate; 10 (13) a salicylate salt monohydrate, 11 and (14) a hydrogen phthalate salt. [3][4][5][6][7][8][9][10][11] So far, at least fourteen different crystalline structures of lamivudine have been reported: (1) form I, a 0.2 hydrate; 3 (2) form II, an anhydrous polymorh; 3 (3) a saccharinate salt; 4 (4) a 3,5-dinitrosalicylate salt hydrate; 5 (5) a 4-quinolinone cocrystal; 5 (6) a zidovudine cocrystal hydrate; 5 (7) a hydrogen maleate salt; 6 (8) lamivudine duplexes I 7 and (9) II; 8 (10) form III, a hemihydrate; 9 (11) a hydrochloride salt anhydrate 10 and (12) a hydrochloride salt monohydrate; 10 (13) a salicylate salt monohydrate, 11 and (14) a hydrogen phthalate salt.…”