Biopharmaceuticals rate-limiting

Fig. 7.5. The Biopharmaceutics Classification System (BCS) provides a scientific basis for predicting intestinal drug absorption and for identifying the rate-limiting step based on primary biopharmaceutical properties such as solubility and effective intestinal permeability (Pefr). BCS serves as a product control instrument. The BCS divides drugs into four different classes based on their solubility and...

Ideally such a formulation should be universally applicable. This was achieved by the invention of the drug nanocrystals. " With the nanocrystals one went one step beyond micronization in fact to "nanonization". Drug nanocrystals dissolve very fast and thus they can overcome oral bioavailability problems in which the dissolution velocity is the rate limiting step for absorption (e.g. drugs of class II of the Biopharmaceutical Classification System (BCS)). Meanwhile five products for oral administration are on the market. Because of their small size drug nanocrystals can also be injected intravenously. With a size below 1 fim, typically between 200-600 nm, they are much smaller than the smallest blood capillaries being in the range of 5-6 tm. Intravenous products are under development. 

The purpose of Level A correlations is to define a direct relationship between in vitro and in vivo data so that measurement of the in vitro dissolution rate alone is sufficient to determine the biopharmaceutical fate of the dosage form. IVIVCs should be sought as early as possible during the dosage form development (a priori correlations). In some cases, formulation has been undertaken rapidly and correlations sought on the finished product from subsequent in vitro tests. The predictive power of these correlations (a posteriori correlations) is thus limited, and they require additional validation. 

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