Soluble Salts and Cocrystals of Clotrimazole

• DOI: 10.1021/acs.cgd.5b00268
• Publication Date: 2015-04-13T15:52:11Z
• Authors: Sudhir Mittapalli; M. K. Chaitanya M...; U. B. Rao Khandav...; Suryanarayana Allu; Ashwini Nangia
• Keywords: Clotrimazole; Cocrystal; Adipic acid

Novel crystalline adducts of clotrimazole with pharmaceutically acceptable coformers were prepared. Five salts and two cocrystals the antimycotic drug (CLT) crystallized carboxylic acid adipic (ADA), 2,5-dihydroxybenzoic (25DHBA), 2,4,6-trihydroxybenzoic (246THBA), p-coumaric (PCA), caffeic (CFA), maleic (MA), suberic (SBA). Molecular overlay diagram in four (CLT–25DHBA, 1:1; CLT–246THBA, CLT–PCA, CLT–CFA–ANI, 1:1:1) CLT–ADA (1:0.5) cocrystal showed conformational flexibility phenyl rings triaryl methane molecule. The X-ray crystal structures are sustained by N+–H···O–/ N–H···O hydrogen bonds. solid-state forms well characterized analyzed PXRD, FT-IR, DSC confirmed single diffraction (except for CLT–MA CLT–SBA adducts). 15N ss-NMR indicated intermolecular proton transfer CLT–MA, chemical shifts consistent salt formation. acidic CLT base selected based on ΔpKa rule 3. Solubility measurements improved solubility a factor 2.9 (CLT–25DHBA), 14.0 (CLT–246THBA), 1.3 (CLT–PCA), 2.8 (CLT–CFA), 22.4 (CLT–MA) 5.0 (CLT–ADA CLT–SBA) compared to 65% EtOH–water.