Dissolution rate-limited absorption

G. Levy, J. R. Leonards, and J. A. Procknal, Development of in vitro dissolution tests which correlate quantitatively with dissolution rate-limited drug absorption in man, J. Pharm. Sci., 54, 1719-1722 (1966). K. A. Javaid and D. E. Cadwallader, Dissolution of aspirin from tablets containing various buffering agents, J. Pharm. Sci., 61, 1370-1373 (1972). 

The intrinsic dissolution rate is the rate of mass transfer from the solid phase to the liquid phase. Information on the intrinsic dissolution rate is important in early drug product development. It has been suggested that drugs with intrinsic dissolution rates of less than 0.1 mg/(min cm2) will have dissolution rate-limited absorption, while drugs with intrinsic dissolution rates greater than 0.1 mg/ (min cm2) are unlikely to have dissolution rate problems. 

The physiologically based model developed by Willman et al. [53, 54], for the prediction of both rat and human Fibs, was shown to be predictive for the human situation if passively transported compounds were studied. In their study, they used a semiempirical formula for the prediction of human permeability trained with a set of 119 passively transported drugs that did not show solubility or dissolution rate-limited absorption. 

When a drug is more rapidly or completely absorbed from solution, it is very likely that its absorption will be dissolution rate limited. 

For formulating poor water-soluble compounds, use of cosolvent(s) is one of the simplest and common approach. The approach is also widely used in the early development phase, as limited information is available for the molecule. The approach also allows overcoming dissolution rate limited drug absorption. In addition, solubilized formulations are greatly popular with pediatric, geriatric, and patients with swallowing difculties. 

While employing this approach for enhancing oral bioavailability of poorly soluble drugs, in which drug absorption is dissolution-rate limited, the following considerations must be taken into account ... 

As discussed above, the rate-limiting step in the oral absorption of Class II drug substances is likely to be the in vivo dissolution [23-25]. For Class II dissolution rate limited drugs, hence, if in vivo dissolution can be estimated in vitro, an in vitro-in vivo correlation may be established. As discussed in Section 3.5, such media have been developed, and an adequate IVIVC was shown for number of Class II drugs. However, due to the numerous in vivo parameters involved, it appears that more research is needed to develop uniform dissolution media reflecting in vivo dissolution conditions, to establish an adequate IVIVC, and to asses the risk of bioinequivalence [86, 88], In addition, the relationship between the hydrodynamics in the currently available dissolution tests and the actual in vivo situation is not adequately characterized and might interfere to obtain the correlation. 

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