Salt and Cocrystals Combining Sulfathiazole with Pyrimethamine

Dihydrofolate reductase inhibitors, such as pyrimethamine, are known to have synergistic effects with sulfonamides. Four new solid forms combining pyrimethamine and sulfathiazole, one cocrystal (pyrimethamine-sulfathiazole (1:1)) and three solvated salt cocrystals (in which pyrimethamine and sulfathiazole are in a 1:2 molar ratio), are determined and characterized. Desolvation of the salt cocrystals leads to either a physical mixture of the starting compounds or the formation of the cocrystal (1:1) with an excess of sulfathiazole. The pyrimethamine sulfathiazole binary phase diagram was determined, which reveals that the pyrimethamine-sulfathiazole (1:2) composition point corresponds to a metastable eutectic. Obtaining this metastable eutectic as a pure powder is therefore rather difficult since it converts to a stable mixture of the (1:1) cocrystal + sulfathiazole. The abovementioned drug–drug multicomponent systems are characterized in terms of thermal stability (by TGA/DSC) and solubility. Both pyrimethamine-sulfathiazole (1:1) cocrystal and pyrimethamine-sulfathiazole (1:2) ethanol-solvated salt cocrystal result in an increase of the parent drugs’ solubility

Expedited orthodontics : improving the efficiency of orthodontic treatment through novel technologies /

This volume includes the proceedings of the Forty-First Annual Moyers Symposium, March 8-9, 2014, Ann Arbor, Michigan.Includes bibliographical references.Mode of access: Internet

Impact of age on the performance of the ESC 0/1h-algorithms for early diagnosis of myocardial infarction

Aims We aimed to evaluate the impact of age on the performance of the European Society of Cardiology (ESC) 0/1halgorithms and to derive and externally validate alternative cut-offs specific to older patients. Methods and results We prospectively enrolled patients presenting to the emergency department (ED) with symptoms suggestive of acute myocardial infarction in three large diagnostic studies. Final diagnoses were adjudicated by two independent cardiologists. High-sensitivity cardiac troponin (hs-cTn) T and I concentrations were measured at presentation and after 1 h. Patients were stratified according to age [<55 years (young), ≥55 to <70 years (middle-age), ≥70 years (old)]. Rule-out safety of the ESC hs-cTnT 0/1h-algorithm was very high in all age-strata: sensitivity 100% [95% confidence interval (95% CI) 94.9-100] in young, 99.3% (95% CI 96.0-99.9) in middle-age, and 99.3% (95% CI 97.5- 99.8) in old patients. Accuracy of rule-in decreased with age: specificity 97.0% (95% CI 95.8-97.9) in young, 96.1% (95% CI 94.5-97.2) in middle-age, and 92.7% (95% CI 90.7-94.3) in older patients. Triage efficacy decreased with increasing age (young 93%, middle-age 80%, old 55%, P < 0.001). Similar results were found for the ESC hs-cTnT 0/1h-algorithm. Alternative, slightly higher cut-off concentrations optimized for older patients maintained very high safety of rule-out, increased specificity of rule-in (P < 0.01), reduced overall efficacy for hs-cTnT (P < 0.01), while maintaining efficacy for hs-cTnI. Findings were confirmed in two validation cohorts (n = 2767). Conclusion While safety of the ESC 0/1h-algorithms remained very high, increasing age significantly reduced overall efficacy and the accuracy of rule-in. Alternative slightly higher cut-off concentrations may be considered for older patients, particularly if using hs-cTnI