Soluble drugs, poorly bioavailability

R. H. Muller, C. Jacobs, and 0. Kayser. DissoCubes—A novel formulation for poorly soluble and poorly bioavailable drugs, in Michael J. Rathbone, Jonathan Hadgraft, and Machael S. Roberts (eds.), Drugs and the Pharmaceutical Sciences, Vol. 126 Modified-Release Drug Delivery Technology. New York Marcel Dekker, 2003, pp. 139-149. 

For highly permeable, poorly soluble drugs given in lower doses, the dissolution rate rather than the saturation solubility is the limiting factor. An increase in dissolution rate due to in vivo solubilization mediated by food intake could theoretically be obtained, but this situation is not always found in vivo. For example, food does not affect the rate and extent of bioavailability for candesartan cilexitil, a very poorly soluble compound [78], An in vitro dissolution and solubility study of this compound in simulated intestinal media provided a potential explanation it was revealed that the solubility was increased as a function of bile concentration as expected, whereas the dissolution rate was not increased by the higher bile concentrations being representative for the fed state (see Fig. 21.14). Thus, although... 

Serajuddin, A.T.M., Sheen, P, Mufson, D., Bernstein, D.F., and Augustine, M.A., Physicochemical basis of increased bioavailability of a poorly water-soluble drug following oral administration as organic solutions, /. Pharm. Sci., 77, 325, 1988. 

Another method of improving bioavailability for these poorly soluble drugs is to prepare an amorphous formulation, since an amorphous form allows fasterdissolution of the drug in comparison to its corresponding crystalline form. An amorphous formulation is prepared by incorporating the... 

Oral bioavailability of poor water-soluble drugs can be improved by enhancement of the dissolution rate and/or apparent solubility (via supersaturation in the gastrointestinal Luids). 

Joshi, H. N., R. W. Tejwani, M. Davidovich, V. P. Sahasrabudhe, M. Jemal, M. S. Bathala, S. A. Varia, and A. T. M. Serajuddin. 2004. Bioavailability enhancement of a poorly water-soluble drug by solid dispersion in polyethylene glycol-polysorbate 80 mixtdnfc. J. Pharm. 269 251-258. 

For many poorly soluble drugs, the dissolution rate best reLects the bioavailability of the compound (Juncher and Raaschou, 1957 Benge et al., 1977). Indeed, solubility might affect absorption only to the extent that it affects the dissolution rate. Since absorption is a dynamic process, the solubility of a drug might be of limited consequence if the absorption rate is so rapid that solubility is not attained in the biological Luid. The dissolution rate in this instance would be critical since it could establish the effective absorption rate (Berge et al., 1977). 

The dependence of dissolution rate to speciLc surface area is the basis for pursuing particle size reduction as a method of increasing the bioavailability of poorly water-soluble drugs. 

Chaumeil, J. C. (1998) Micronization A method of improving the bioavailability of poorly soluble drugs, Methods Find. Exp. Clin. Pharmacol., 20 211-215. 

FIGURE 18.1 Advantages of a solid dispersion formulation, as compared to conventional capsule or tablet formulations, for enhancing dissolution rate, and consequent bioavailability of poorly water-soluble drugs. (From Serajuddin A. T. M. 19991 Pharm ScB8 1058-1066. With permission.)... 

Vasanthavada, M. and A. T. M. Serajuddin. Lipid-based self-emulsifying solid dispersidripid-n Based Formulations for Oral Drug Delivery Enhancing the Bioavailability of Poorly Vteter-Soluble Drugs, ed. D. J. Flauss, 149-183. New York Informa Healthcare. 

Serajuddin, A. T. M., P. C. Sheen, D. Mufson. D. F. Bernstein, and M. A. Augustine. 1988. Effect of vehicle amphiphilicity on the dissolution and bioavailability of a poorly water-soluble drugs from solid dispersionsJ Pharm Sci77 414-417. 

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