MS05-P04 Co-crystal forms of the BCS class IV drug sulfamethoxazoleSulfamethoxazole, smz, is an antibiotic which is classified as a Biopharmaceutics Classification System (BCS) class IV, low solubility and low permeability drug. Co-crystal formation has been examined in an attempt to improve solubility. Both ball milling and crystallization from solution have been examined. Ball milling showed that thirteen co-formers gave new crystalline X-ray powder patterns and four gave X-ray amorphous patterns while crystallization from solution gave single crystals of four co-crystals and a salt. The co-formers which gave the co-crystals and the salt have better H-bond acceptors than the sulfonyl oxygens of smz. The 4,4-dipyridyl co-crystal has an interesting high Z’’ structure. It crystallized in space group P1 with four smz and six 4,4’-dipyridyl molecules in the asymmetric unit.The lattice energies of smz and the co-crystals were estimated using the PIXEL program.The dissolution rates of the co-crystals are all lower than smz form I despite the fact that they have lower computed lattice energies than smz form I. It appears that the absence of any hydrogen bond in the smz form I structure with a D…A distance less than 3.2 Å and the presence of stronger hydrogen bonds in the co-crystals with D…A distances close to 2.8 Å is more important in determining dissolution rates than lattice energies.References:
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