Abstract
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.
Similar content being viewed by others
REFERENCES
R. A. Lahti, V. H. Sethy, C. Barsuhn, and J. B. Hester. Pharmacological profile of the antidepressant adinazolam, a triazolobenzodiazepine. Neuropharmacology 22:1277–1282 (1983).
J. D. Amsterdam, M. Kaplan, L. Potter, L. Bloom, and K. Rickels. Adinazolam, a new triazolobenzodiazepine, and imipramine in the treatment of major depressive disorder. Psychopharmacology 88:484–488 (1986).
D. Dunner, J. Myers, A. Khan, D. Avery, D. Ishiki, and R. Pyke. Adinazolam—A new antidepressant: Findings of a placebo-controlled, double-blind study in out patients with major depression. J. Clin. Psychopharmacol. 7:170–172 (1987).
R. E. Pyke and H. S. Greenberg. Double-blind comparison of alprazolam and adinazolam for panic and phobic disorders. J. Clin. Psychopharmacol. 9:15–21 (1989).
D. V. Sheehan, A. B. Raj, K. Harnett-Sheehan, S. Soto, and C. P. Lewis. Adinazolam sustained release formulation in the treatment of generalized anxiety disorder. J. Anx. Disorders 4:239–246 (1990).
J. C. Fleishaker and J. P. Phillips. Extent and variability of the first-pass elimination of adinazolam mesylate in healthy male volunteers. Pharm. Res. 8:162–167 (1991).
J. G. Wagner, M. C. Rogge, R. B. Natale, K. S. Albert, and G. J. Szpunar. Single dose and steady-state pharmacokinetics of adinazolam after oral administration to man. Biopharm. Drug Dispos. 8:405–425 (1987).
J. C. Fleishaker, J. P. Phillips, T. C. Smith, and R. B. Smith. Multi-dose pharmacokinetics and pharmacodynamics of adinazolam in elderly subjects. Pharm. Res. 6:379–386 (1989).
H. Lapidus and N. G. Lordi. Drug release from compressed hydrophilic matrices. J. Pharm. Sci. 57:1292–1301 (1968).
J. L. Ford, M. H. Rubinstein, F. McCaul, J. E. Hogan, and P. J. Edgar. Importance of drug type, tablet shape and added diluents on drug release kinetics from hydroxypropylmethylcellulose matrix tablets. Int. J. Pharm. 40:223–234 (1987).
R. W. Korsmeyer, R. Gurny, E. Doelker, P. Buri, and N. A. Peppas. Mechanisms of potassium chloride release from compressed, hydrophilic, polymeric matrices: effect of entrapped air. J. Pharm. Sci. 72:1189–1191 (1983).
K. Padmalatha Devi, K. V. Ranga Rao, et al. Zero-order release formulation of oxprenolol hydrochloride with swelling and erosion Control. Pharm. Res. 6:313–317 (1989).
D. A. Alderman. A review of cellulose ethers in hydrophilic matrices for oral controlled-release dosage forms. Int. J. Pharm. Tech. Prod. Mfr. 5:1–9 (1984).
K. V. Ranga Rao and K. Padmalatha Devi. Swelling controlled-release systems: Recent developments and applications. Int. J. Pharm. 48:1–13 (1988).
J. E. Hogan. Hydroxypropylmethylcellulose sustained release technology. Drug Dev. Ind. Pharm. 15:975–999 (1989).
E. L. Doelker. Water-swollen cellulose derivatives in pharmacy. In N. A. Peppas (ed.), Hydrogels in Medicine and Pharmacy, Vol. II. Polymers, CRC Press, Boca Raton, FL, 1987, Chap. 5.
P. L. Ritger and N. A. Peppas. A simple equation for description of solute release. I. Fickian and non-Fickian release from non-swellable devices in the form of slabs, spheres, cylinders or discs. J. Control. Release 5:23–36 (1987).
P. L. Ritger and N. A. Peppas. A simple equation for description of solute release. II. Fickian and anomalous release from swellable devices. J. Control. Release 6:37–42 (1987).
K. J. Simons, E. M. Frith, and F. E. R. Simons. Dissolution and bioavailability studies of whole and halved sustained-release theophylline tablets. J. Pharm. Sci. 71:505–511 (1982).
V. P. Shah, L. A. Yamamoto, D. Schuirman, J. Elkins, and J. P. Skelly. Analysis of in vitro dissolution of whole vs. half controlled-release theophylline tablets. Pharm. Res. 4:416–419 (1987).
T. A. Moreland, M. E. T. McMurdo, and J. McEwen. Multiple dose comparison of a whole 240 mg verapimil sustained-release tablet with two half tablets. Biopharm. Drug Dispos. 10:311–319 (1989).
R. M. Franz, J. A. Sytsma, B. P. Smith, and L. J. Lucisano. In vitro evaluation of a mixed polymeric sustained release matrix using response surface methodology. J. Control. Release 5:159–172 (1987).
J. C. Fleishaker, J. P. Phillips, and H. S. H. Lau. Effect of food on the bioavailability of adinazolam from a sustained release formulation: Effect of meal timing and lack of dose dumping. Biopharm. Drug Disp. 11:715–727 (1990).
F. Langenbucher and H. Moller. Correlation of in vitro drug release with in vivo response kinetics. Pharm. Ind. 45:629–633 (1983).
J. C. Fleishaker, H. L. Friedman, S. R. Pollock, and T. C. Smith. Clinical pharmacology of adinazolam and N-desmethyladinazolam mesylate after single oral doses of each compound in healthy volunteers. Clin. Pharmacol. Ther. 48:652–664 (1990).
J. G. Wagner and E. Nelson. Per cent absorbed time plots derived from blood level and/or urinary excretion data. J. Pharm. Sci. 52:610–611 (1963).
J. G. Wagner. Pharmacokinetic absorption plots from oral data alone or oral/intravenous data and an exact Loo-Riegelman equation. J. Pharm. Sci. 72:838–842 (1983).
K. Yamaoka, T. Nakagawa, and T. Uno. Application of Akaike's information criterion (AIC) in the evaluation of linear pharmacokinetic equations. J. Pharmacokinet. Biopharm. 6:165–175 (1978).
W. I. Higuchi. Analysis of data on the medicament release from ointments. J. Pharm. Sci. 51:802–804 (1962).
T. Higuchi. Mechanism of sustained action medication. Theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J. Pharm. Sci. 52:1145–1149 (1963).
J. Neter and W. Wasserman. Applied Linear Statistical Models, Richard D. Irwin, Homewood, IL, 1974, Chap. 5.
J. P. Skelly, G. L. Amidon, W. H. Barr, L. Z. Benet, J. E. Carter, J. R. Robinson, V. P. Shah, and A. Yacobi. In vitro and in vivo testing and correlation for oral controlled/modified-release dosage forms. Pharm. Res. 7:975–982 (1990).
J. P. Skelly. Bioavailability of sustained release dosage forms-relationship with in vitro dissolution. In A. Yacobi and E. Halperin-Walega (eds.), Oral Sustained Release Formulations: Design and Evaluation, Pergamon Press, New York, 1988, Chap. 3.
V. W. Steinijans, R. Dietrich, H. Trautmann, R. Sauter, and G. Benedikt. A novel approach to the specification of in vitro dissolution boundaries based on regulatory requirements for bioequivalance. Arzneim.-Forsch/Drug Res. 38:1238–1240 (1988).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Skoug, J.W., Borin, M.T., Fleishaker, J.C. et al. In Vitro and in Vivo Evaluation of Whole and Half Tablets of Sustained-Release Adinazolam Mesylate. Pharm Res 8, 1482–1488 (1991). https://doi.org/10.1023/A:1015834114359
Issue Date:
DOI: https://doi.org/10.1023/A:1015834114359