Abstract
Purpose. To assess the usefulness of biorelevant dissolution tests in predicting food and formulation effects on the absorption of four poorly soluble, lipophilic drugs.
Methods. Dissolution was studied with USP Apparatus II in water, milk, SIFsp, FaSSIF, and FeSSIF. The in vitro dissolution data were compared on a rank order basis with existing in vivo data for the tested products under fasted and fed state conditions.
Results. All drugs/formulations showed more complete dissolution in bile salt/lecithin containing media and in milk than in water and SIFsp (USP 23). Comparisons of the in vitro dissolution data in biorelevant media with in vivo data showed that in all cases it was possible to forecast food effects and differences in absorption between products of the same drug with the physiologically relevant media (FaSSIF, FeSSIF and milk). Differences between products (both in vitro or in vivo) were less pronounced than differences due to media composition (in vitro) or dosing conditions (in vivo).
Conclusions. Although biorelevant dissolution tests still have issues which will require further refinement, they offer a promisingin vitro tool for forecasting the in vivo performance of poorly soluble drugs.
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REFERENCES
M. C. Meyer, A. B. Straughn, R. M. Mhatre, V. P. Shah, R. L. Williams, and L. J. Lesko. Lack of in vivo/in vitro correlations for 50 mg and 250 mg primidone tablets. Pharm. Res. 15:1085-1089 (1998)
J. B. Dressman, G. L. Amidon, C. Reppas, and V. P. Shah. Dissolution as a prognostic tool for oral drug absorption: immediate release dosage forms. Pharm. Res. 15:11-22 (1998)
E. Galia, E. Nicolaides, D. Hörter, R. Löbenberg, C. Reppas, and J. B. Dressman. Evaluation of various dissolution media for predicting in vivo performance of class I and class II drugs. Pharm. Res. 15:698-705 (1998)
M. D. Johnson, L. K. Campbell, and R. K. Campbell. Troglitazone: review and assessment of its role in the treatment of patients with impaired glucose tolerance and diabetes mellitus. Ann. Pharmacother. 32:337-348 (1998)
C. M. Spencer, and K. L. Goa. Atovaquone. A review of its pharmacological properties and therapeutic efficacy in opportunistic infections. Drugs 50:176-196 (1995)
S. Tamura, S. Miyazaki, K. Tateda, A. Ohno, Y. Ishii, T. Matsumoto, N. Furuya, and K. Yamaguchi. In vivo antibacterial activities of sanfetrinem cilexetil, a new oral tricyclic antibiotic. Antimicrob. Agents Chemother. 42:1858-1861 (1998)
L. Iavarone, M. Bottacini, F. Pugnaghi, C. Morandini, and P. Grossi. Sanfetrinem and sanfetrinem-cilexetil: disposition in rat and dog. Xenobiotica 27:693-709 (1997)
G. L. Amidon, H. Lennernäs, V. P. Shah, and J. R. A. Crison. Theoretical basis for a biopharmaceutics drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm. Res. 12:413-420 (1995)
P. Macheras, M. Koupparis, and C. Tsaprounis. Drug dissolution studies in milk using the automated flow injection serial dynamic dialysis technique. Int. J. Pharm. 33:125-136 (1986)
P. E. Macheras, M. A. Koupparis, and S. G. Antimisiaris. Drug binding and solubility in milk Pharm. Res. 7:537-541 (1990)
Y. Fu, C. Shen, T. Fujita, and C. S. Foote. Photooxidation of troglitazone, a new antidiabetic drug. Photochem. Photobiol. 63:615-620 (1996)
A. T. Florence and D. Attwood. Physicochemical principles of pharmacy (2nd Edition), Macmillan Press Ltd., London, 1988
M. A. Young, S. Lettis, and R. Eastmond. Improvement in the gastrointestinal absorption of troglitazone when taken with, or shortly after food. Br. J. Clin. Pharmacol. 45:31-35 (1998)
P. E. Rolan, A. J. Mercer, B. C. Weatherley, T. Holdich, H. Meire, R. W. Peck, G. Ridout, and J. Posner. Examination of some factors responsible for a food-induced increase in absorption of atovaquone. Br. J. Clin. Pharmacol. 37:13-20 (1994)
E. Galia, C. Hoth, N. Künnen, A. Nöske, R. Schulte, S. Stein, M. Wunderlich, J. Horton, and J. B. Dressman. Comparative in vitro dissolution study of various albendazole products. PharmSci. (Suppl.) 1:S-491 (1998)
P. Walstra, R. Jennes, and H.T. Badings. Dairy chemistry and physics, John Wiley and Sons, New York, 1984
J. Borovicka, W. Schwizer, C. Mettraux, C. Kreiss, B. Remy, K. Asal, J. B. Jansen, I. Douchet, R. Verger, and M. Fried. Regulation of gastric and pancreatic lipase secretion by CCK and cholinergic mechanisms in humans. Am. J. Physiol. 273:G374-G380 (1997)
T. Ono, Y. Takagi, and I. Kunishi. Casein phosphopeptides from casein micelles by successive digestion with pepsin and trypsin. Biosci. Biotechnol. Biochem. 62:16-21 (1998)
G. Miranda and J. P. Pelissier. Kinetic studies of in vivo digestion of bovine unheated skim-milk proteins in the rat stomach. J. Dairy Res. 50:27-36 (1983)
J. S. Fordtran and T. Locklear. Ionic constituents and osmolarity of gastric and small intestinal fluids after eating. Am. J. Dig. Dis. 11:503-521 (1966)
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Nicolaides, E., Galia, E., Efthymiopoulos, C. et al. Forecasting the In Vivo Performance of Four Low Solubility Drugs from Their In Vitro Dissolution Data. Pharm Res 16, 1876–1882 (1999). https://doi.org/10.1023/A:1018959511323
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DOI: https://doi.org/10.1023/A:1018959511323