Abstract
A biopharmaceutic drug classification scheme for correlating the in-vitro drug product dissolution and in-vivo bioavailability for IR products was proposed by Amidon et al (1995). The classification arose from drug dissolution and absorption models which identified the key parameters controlling drug absorption as the dimensionless numbers; the Absorption number (An ), the Dissolution number (Dn) and the Dose number (Do). This led to a biopharmaceutic classification of drugs into four groups, the establishment of a basis for determining the conditions under which in-vitro-in-vivo (IVIV) correlation’s are expected and the use of the classification to set drug bioavailability standards for IR products. These developments raise the issue of whether the biopharmaceutic classification has relevance to ER products. In contrast to IR products, drugs selected for ER products should have good gastrointestinal (GI) permeability and an extended site of absorption. However their permeability(Papp) may change depending on the site. Solubility(Cs), effective fluid volume and hence Do may also vary with site. Of particular relevance to both permeability and solubility is the degree of ionization of the drug. Residence time at each site, pH changes and the potential for drug degradation at different sites, the latter resulting in a restricted absorption window, will influence the time frame over which an IVIV relationship is possible. Of the drugs available in ER dosage forms ∼ 63% are bases, 15% acids and the remainder either unionizable or small inorganic ions. Acidic drugs will tend to have lower solubility’s high up in the gastrointestinal tract (GIT), with solubility increasing down the GIT. In contrast with increased ionization permeability should fall. Thus with acids, as the dosage form moves to a more alkaline environment down the GIT, absorption may change from dissolution control to membrane control depending on the pKa of the drug. In contrast bases will loose solubility with transit down the GIT, but become more permeable; absorption becoming more dissolution/release controlled or in ex- treme cases solubility controlled in the latter stages of the absorption phase. In the light of the above considerations a modified biopharmaceutic classification is proposed for ER products.
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References
Amidon, G.L., Lennernas, H. Shah, V.P. and Crison, J.P., Pharm. Res. 12, 413–420 (1995).
Rudman, A and Williams, R.L. Guidance for Industry Immediate Release Solid Dosage Forms. CDER Nov. 1995.
Federal Register. 60, 21638-21643.
Sinko, P.J. Leesman, G.D., and Amidon, G.L. Pharm. Res. 8, 979–988 (1991).
Oh, D.M., Curl, R.L. and Amidon, G.L. Pharm. Res. 10, 264–270 (1993).. Ho, N.F.H., Merkle, H.P. and Higuchi, W.I. Drug Devel. & Ind. Pharm. (1111-1184) (1983).
Higuchi, W.I. & Hiestand, E.N., J.Pharm. Sci., 52, 67–71(1963).
Physicians Desk Reference, 50th Ed, Medical Economics Company, N.J., 1996.
Davis, S.S., Hardy, J.G. and Fara, J.W Gut, 27, 886-892(1986)
Hardy, J.G., Wilson, CG. and Wood, E., J.Pharm. Pharmac, 37, 874–877 (1985).
Steed K.P., Wilson C.G., and Washington, N. Ch. 6 in Physiological Pharmaceutics, Biological Barriers to Drug Absorption, Ed. Wilson, C.G. and Washington N., 1989, Ellis Horwood Ltd., Series in Pharmaceutical Technology, Chichester
Ho, N.F.H., Park, J.Y., Morozowich, W. and Higuchi, W.I., Chapter 8 in Design of Biopharmaceutical Properties through Prodrugs and Analogues Ed. B. Roche A.Ph.A. 1977.
Soergel, K.H., Gastroenterology, 105, 1247–1249 (1993).
Kramer, W.G., J.Clin. Pharmacol. 34, 1218–1221(1994).
Fischer, W., Boertz, A. Davis, S.S., Khosla, R., Caawello, W., Sandrock, K., Cordes, G. Pharm. Res., 4, 480–485(1987)
Wilson C.G. in drug Delivery to the Gastrointestinal Tract. Chapter 13, Eds., J.G. Hardy, S.S. Davis and C.G. Wilson, Ellis Horwood Ltd., Series in Pharmaceutical Technology, Chichester, p. 161, 1989.
Uch, A.S. & Dressman, J.B. In Formulation of poorly — Available Drugs For Oral Administration, Minutes, Ed. P. Couvrer, D. Duchene and I. Kalles, Editions de Santé, p. 152, Paris 1996.
Ramtoola, Z. and Corrigan O.I., Drug Devel. and Ind. Pharm., 15, 2359–2374(1989).
Fara, J.W., Colonic drug absorption and metabolism. Ch. 10, 103-112. in Novel Drug Delivery and its Therapeutic Applications. Ed. Prescott, JE & Nimmo, WS 1989 Wiley &Sons Ltd.
Dunne, A., Corrigan, O.I., Bottini P.B. and Geoghegan, E.J. Proc. 2nd European Congress of Biopharmaceutics and Pharmacokinetics. Volume 1., 421–427,(1984).
Wagner, J.G. and Nelson, E., J. Pharm. Sci 1963.
Devane J., unpublished.
Barr, W. H., Zola, E.M., Candler, E.L. Hwang, S.M., Tendolkar, A.V., Shamburek, R. Parker, B. Hilty M.D., Clin.Pharmacol. Therap. 56, 279–85 (1994).
Peh, K.K., Ph. D. Thesis, Universiti Sains Malaysia, 1996.
Devane, J. unpublished.
Godbillon, J., Gerardin, A. Richard, J. Leroy, D. and Moppert, J., Br. J. Clin. Pharmac. 19, 213–2185, (1985).
Bradbrook, D. John, V.A. Morrison, P.J. Rogers, H.J. & Spector, R.G., Br. J. Clin Pharmac. 19, 163s–169s (1985).
Corrigan, O.I., Dunne, A., McLoughlin, H. Geoghegan, E., Killian, C.A. and Panoz, D.E. Controlled Release Delivery Systems, Chapter 10, 163–167, Ed Roseman, T.J. and Mansdorf, S.Z., Marcel Dekker, Inc. (1983).
Fagerholm, U. and Lennernas, H., Eu. J. Pharm. Sci. 3, 247–253(1995).
Corrigan, O.I. Drug Devel. Ind. Pharm 18, 695–708, (1992).
Levy, G. J.Mond.Pharm. 3 237–254(1967).
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Corrigan, O.I. (1997). The Biopharmaceutic Drug Classification and Drugs Administered in Extended Release (Er) Formulations. In: Young, D., Devane, J.G., Butler, J. (eds) In Vitro-in Vivo Correlations. Advances in Experimental Medicine and Biology, vol 423. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-6036-0_9
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