The fundamental variables of the biopharmaceutics classification system (BCS): a commentary.

Based on in vitro solubility and in vivo permeability drugs can be divided into four groups: class 1 (high permeability, high solubility, HP:HS), class 2 (high permeability, low solubility, HP:LS), class 3 (low permeability, high solubility, LP:HS), and class 4 (low permeability, low solubility, LP:LS) (Amidon et al., 1995; Amidon, G.L., Lennernas, H., Shah, V.P., Olson, J.R., 1995. Pharm. Res. 12, 413-420). The high permeability boundary has been suggested to be 70% (Walter et al., 1996; Walter, E., Janich, S., Roessler, B.J., Hilfinger, J.H., Amidon, G., 1996. J. Pharm. Sci. 85, 1070-1076) or 90% (Hussain et al., 1997; Hussain, A.S., Kaus, L.C., Lesko, L.J., Williams, R.L., 1997. Eur. J. Pharm. Sci. 5 (Suppl. 2), S43-S44), and more recently was compromised by the FDA to 80% human intestinal absorption (Hussain, A.S., 1998. Information presented at the BCS and in vitro-in vivo correlations workshop. Frankfurt/M., Germany, March 1998). The biopharmaceutics classification system (BCS) is now being considered by the FDA to develop new regulatory guidance for bioequivalence studies (Hussain, 1998; Lesko, 1997; Lesko, L.J., 1997. Eur. J. Pharm. Sci. 5 (Suppl. 2), S42). Both properties, solubility and permeability, are being considered as fundamental to define the rate and extent of absorption of the active ingredient of a drug product. However, since both these properties are dependent ones, it may be questioned whether these are indeed sufficiently 'fundamental' or should be further unravelled.