Solid-state phase transitions initiated by water vapor sorption of crystalline L-660,711, a leukotriene D4 receptor antagonist.
Significant water vapor sorption at room temperature by the crystalline and lyophilized forms of L-660,711, a potent, selective leukotriene D4 receptor antagonist, has been measured and shown to produce increasingly more nonflowing, semisolid masses with increasing relative humidity. Thermal analysis, SEM, powder X-ray diffraction, solid-state NMR, and thermomicroscopic measurements reveal that water vapor sorbed at room temperature converts the crystalline form to a noncrystalline form resembling the lyophilized sample. Evidence is presented to indicate that L-660,711 has surface active properties with a critical micellization concentration of approximately 1 x 10(-4) M and an ability to form thermotropic and lyotropic mesomorphic phases when the crystal is heated above 80 degrees C in the anhydrous state; it is lyophilized from aqueous solution, and it is exposed to relative humidities at and above 12%, at room temperature.
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Merck Frosst Canada Inc., Pointe Claire-Dorval, PQ.
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Zografi
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D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D004355:Drug Stability; D006358:Hot Temperature; D008855:Microscopy, Electron, Scanning; D011422:Propionates / Q000737:chemistry*; D011804:Quinolines / Q000737:chemistry*; D013189:SRS-A / Q000037:antagonists & inhibitors*; D014835:Volatilization; D014867:Water; D014961:X-Ray Diffraction
D011422:Propionates; D011804:Quinolines; D013189:SRS-A; D014867:Water; C059141:verlukast