Abstract
The dissolution and bioavailability of etodolac from capsules exposed to high relative humidity and temperature were compared to those from capsules stored at room temperature (RT). Dissolution of stressed and control capsules was evaluated using a USP basket apparatus at 100 rpm with 900 mL pH 7.5 phosphate buffer (0.05 M) at 37°C. The dissolution of etodolac from capsules exposed to stressed conditions was also evaluated with enzymes (pancreatin, 1%, w/v) added to the dissolution medium. The bioavailability of etodolac from capsules exposed to stressed conditions was compared in both dogs and humans to capsules stored at RT conditions. Capsules, 200 and 300 mg, exposed to stressed conditions failed the dissolution (without enzymes) specification [not less than 85% released (80% Q) in 30 min]. However, upon enzyme addition, all capsules met the specification. The rate and extent of absorption from these 200 and 300 mg etodolac capsules in dogs were equivalent to those from capsules stored at RT conditions that passed the dissolution specification. Similarly, the bioavailability of etodolac from 300 mg capsules that failed the dissolution specification upon exposure to stressed conditions was equivalent to that of control capsules in 24 adult male volunteers. Thus, an in vitro dissolution test with enzymes provides a better indication of stressed capsule performance in vivo.
Similar content being viewed by others
REFERENCES
Elanco Qualicaps, Technical Service Reference Manual (1991).
Guideline for Submitting Documentation for the Stability of Human Drugs and Biologics, Center for Drugs and Biologics, Food and Drug Administration, 1987, pp. 11, 43.
E. M. Marks, D. Tourtellotte, and A. Andux. The phenomenon of gelatin insolubility. Food Tech. 22:1433–1436 (1968).
R. Clark and A. Courts. The chemical reactivity of gelatin. In A. Ward and A. Courts (eds.), The Science and Technology of Gelatin, Academic Press, New York, 1977, pp. 209–247.
K. S. Murthy, N. A. Enders, and M. B. Fawzi. Dissolution stability of hard-shell capsule products. I. The effect of exaggerated storage conditions. Pharm. Tech. 13 (3):72–86 (1989).
K. S. Murthy, R. G. Reisch, Jr., and M. B. Fawzi. Dissolution stability of hard-shell capsule products. II. The effect of dissolution test conditions on in vitro drug release. Pharm. Tech. 13 (6):53–58 (1989).
S. A. H. Khalil, L. M. M. Ali, and M. M. A. Khalek. Effects of aging and relative humidity on drug release. I. Chloramphenical capsules. Pharmazie 29:36–37 (1974).
P. York. The shelf life of some antibiotic preparations stored under tropical conditions. Pharmazie 32:101–104 (1977).
M. Georgarakis, P. Hatzipantou, and J. E. Kountourelis. Effect of particle size, content in lubrication, mixing time and storage relative humidity on drug release from hard gelatin ampicillin capsules. Drug Dev. Ind. Pharm. 14:915–923 (1988).
A. Ludwig and M. Van Ooteghem. Disintegration of hard gelatin capsules. Pharm. Ind. 43:188–190 (1981).
United States Pharmacopeia XXII, Mack, 1989, Sect. 711, pp. 1578–1579.
L. Cosyns, M. Spain, and M. Kraml. Sensitive high performance liquid chromatographic method for the determination of etodolac in serum. J. Pharm. Sci. 72:275–277 (1983).
D. J. Schuirmann. A comparison of the two one-sided tests procedure and the power approach for assessing the equivalence of average bioavailability. J. Pharmacokinet. Biopharm. 15:657–680 (1987).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Dey, M., Enever, R., Kraml, M. et al. The Dissolution and Bioavailability of Etodolac from Capsules Exposed to Conditions of High Relative Humidity and Temperatures. Pharm Res 10, 1295–1300 (1993). https://doi.org/10.1023/A:1018913628568
Issue Date:
DOI: https://doi.org/10.1023/A:1018913628568