In vitro and in vivo evaluation of whole and half tablets of sustained-release adinazolam mesylate.
The mechanism of release from sustained-release adinazolam mesylate tablets was assessed by the Higuchi equation and by analysis of drug release profiles through 60% released using the Peppas equation. Computed values of the diffusional exponent, n, ranged from 0.59 to 0.66. Values of n in this range are consistent with a mixed mechanism of release, with diffusion of drug through the hydrated polymer matrix and relaxation of this matrix being the principal processes controlling release. The rate of in vitro drug release was increased for half tablets relative to whole tablets and is attributed to an increase in the surface to volume ratio of half tablets of about 16%. This increase in surface-to-volume ratio of half tablets was reflected by an increase in the constant, k, from the Peppas equation of 20-23% and by an increase in the slope of Higuchi plots of 12-18% for four lots of tablets. In vivo/in vitro relationships from two bioavailability studies were thoroughly evaluated. Using either a linear or a quadratic relationship, an in vivo/in vitro correlation exists for sustained-release adinazolam mesylate tablets.
Skoug
J W
JW
Upjohn Company, Kalamazoo, Michigan 49001.
Borin
M T
MT
Fleishaker
J C
JC
Cooper
A M
AM
D000293:Adolescent; D000328:Adult; D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents / Q000493:pharmacokinetics*; D001569:Benzodiazepines / Q000493:pharmacokinetics*; D001682:Biological Availability; D003692:Delayed-Action Preparations; D006801:Humans; D008297:Male; D012995:Solubility
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D003692:Delayed-Action Preparations; D001569:Benzodiazepines; C039668:adinazolam; C074080:adinazolam mesylate