Physical characterization and activity in vivo of polymorphic forms of 7-chloro-5, 11-dihydrodibenz[b, e][1, 4]oxazepine-5-carboxamide, a potential tricyclic antidepressant.
The biological availability in dogs and humans of 7-chloro-5, 11-dihydrodibenz[b,e][1,4]oxazepine-5-carboxamide, a potential antidepressant drug, was increased when the compound was administered in capsule formulations as micronized drug coated with 1% sodium lauryl sulfate or as a lyophilate with poloxamer 407. This increase with these two formulations had been predicted by dissolution tests in vitro. The lyophilized combination with poloxamer 407 was more soluble in 0.1 N HCl than was the untreated compound. Characterization of the lyophilate by differential thermal analysis, X-ray diffraction, and IR spectroscopy indicated that the increase in solubility was attributable to the formation of a polymorphic from. a polymorph of the compound designated form 8, was prepared. The solubility and dissolution characteristics of the two polymorphic forms, A and B, as well as of the lyophilized combination with poloxamer 407, were determined.
D000328:Adult; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000378:metabolism*; D001682:Biological Availability; D002214:Capsules; D003989:Dibenzoxazepines / Q000008:administration & dosage / Q000378:metabolism*; D004285:Dogs; D005612:Freeze Drying; D006801:Humans; D008297:Male; D011060:Poloxalene; D012995:Solubility; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
D000929:Antidepressive Agents, Tricyclic; D002214:Capsules; D003989:Dibenzoxazepines; D011060:Poloxalene