Drug product bioavailability

Characterisation Typical data that may be provided to describe the physical and chemical characteristics of the drug substance are shown in Figure 6.3. The description of the drug product should include the recipe detailing all the other ingredients (excipients) that are used to formulate the final product. It is vital to provide adequate data on the dissolution behaviour of the drug product, as the reviewer may wish to tie this in with pharmacokinetic or bioavailability data submitted in the other modules. 

Amidon, G. L., Lennemas, H., Shah, V. P., Crison, J. R. A. A theoretical basis for a biopharmaceutic drug classification the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm. Res. 1995, 12, 413 20. 

For this calculation, it is unnecessary to assume that Vd and/or kei are the same for the two studies. It is only necessary that fe be the same in both studies. This is usually a valid assumption unless the drug undergoes a significant amount of first-pass metabolism in the gut wall or liver following oral administration or a significant amount of decomposition at an intra muscular (IM) injection site. When this occurs, the availability of the extravascular dosage form may appear to be low, but the fault will not lie with the formulation. The bioavailability will be a true reflection of the therapeutic efficacy of the drug product, and reformulation may not increase bioavailability. 

Bioavailability studies are frequently carried out for the sole purpose of comparing one drug product... 

The topic of generic bioequivalence pertains to the relative bioavailability of different versions of the same drug product, all of which may be available in the marketplace at the same time. Thus, if we continue our consideration of the example introduced in the previous section of this chapter, let us suppose that the innovator did obtain approval to market F3. Initially F3 was the only product available in the marketplace. However, when the relevant patents held by the innovator have expired, other pharmaceutical... 

BCS Class II Low-solubility, high-permeability drugs. The bioavailability of products containing these compounds is likely to be dissolution-rate limited. For this reason, a correlation between in vivo bioavailability and in vitro dissolution rate (IVIVC) may be observed. 

According to a biopharmaceutic expert, the term bioavailability may be defined as the rate and extent to which the ingredient is absorbed from the drug product into the body or to the site of action. It is measured by blood, serum or plasma levels or from urinary excretion data. 

It has now been established beyond any reasonable doubt that quality of a drug product cannot simply be ensured by inspection or analysis, but a control system has to be built into, from the very beginning of manufacture of a drug. Besides effective quality control measures exercised in every aspects of production including environment, screening of raw materials, process controls, intermediate shelf-life of finished products the most important aspect is to assess the bioavailability of the active principle. 

---