Structure and solid-state chemistry of anhydrous and hydrated crystal forms of the trimethoprim-sulfamethoxypyridazine 1:1 molecular complex.
The crystal structure of the equimolar trimethoprim (TMP) and sulfamethoxypyridazine (SMPD) complex in the anhydrous form (TMP. SMPD) and that of the species with 1.5 molecules of water of crystallization (TMP.SMPD.W) are reported in this article. X-ray powder diffraction patterns (both computer generated and experimental) and thermal analytical data from differential scanning calorimetry (DSC) and thermogravimetry useful for the characterization of TMP.SMPD and TMP.SMPD.W are provided. The stability of TMP.SMPD.W, which retains its crystallographic order under 0% relative humidity (RH) conditions at room temperature (22 degrees C) and 20 mmHg, is accounted for in terms of crystal structure and hydrogen bonding. Transformation of TMP.SMPD to the hydrate complex by exposure to approximately 100% RH, suspension in water, and wet granulation, and dehydration of TMP.SMPD.W by thermal treatment and by desiccation with methanol were investigated and tentatively interpreted in terms of crystal properties. Interactions in the physical mixture of TMP and SMPD by grinding, compression, heating, and contact with water were also studied. Water-mediated formation of TMP.SMPD.W by wetting and metastable eutectic melting-mediated formation of TMP.SMPD by heating was demonstrated. Mechanical activation by milling makes the physical mixture prone to solid-state transformation into dimorphic anhydrous cocrystals by supply of thermal energy during a DSC scan.
Bettinetti
G
G
Dipartimento di Chimica Farmaceutica, Università di Pavia, Viale Taramelli 12, I-27100 Pavia, Italy. betti@chifar.unipv.it
Caira
M R
MR
Callegari
A
A
Merli
M
M
Sorrenti
M
M
Tadini
C
C
D003460:Crystallization; D018360:Crystallography, X-Ray; D013421:Sulfamethoxypyridazine / Q000737:chemistry*; D014295:Trimethoprim / Q000737:chemistry*; D014867:Water / Q000737:chemistry
D014867:Water; D014295:Trimethoprim; D013421:Sulfamethoxypyridazine