Tablet testing bioavailability studies

This is the place to start, since most often, analytical chemists are trying to help solve someone else s problem. We need to define the solute and its matrix as well as the nature of the analytical problem. For example, in the world of pharmaceuticals, there are raw material identification and purity determinations, in-process testing, dosage-form determinations, content uniformity, dissolution testing, stability studies, bioavailability, pharmacokinetics, and drug metabolism, to name a few. Each of these analytical problems has its own specific requirements. The matrix can be a raw material, granulation, tablet, capsule, solution, lotion, cream, syrup, dissolution medium, blood serum, urine, or various body tissues and fluids. Similar definitions can be described for virtually any industrial area and problem set. These definitions will help select sample preparation, separation, and detection techniques. 

Product bioavailability is mentioned, especially where it is low. Where there are differences between the formulations tested for bioavailability during the development process and the formulation to be marketed, there is considerable discussion of the data provided on the bioequivalence of the different products and/or formulations. This is particularly so where, for example, early clinical studies were undertaken with capsules but the marketed dosage form is to be a tablet. Bioequivalence data and pharmacokinetic data (e.g., in crossover studies) and comparative dissolution studies are usually reported. This is particularly significant where the different strengths of the final products are not achieved by using different quantities of the same granulate formulation. Process optimization may also be addressed in such cases. 

The relative bioavailability of different enteric diclofenac products was investigated with normal and artificially decreased gastric acidity [63], Only one generic product was found to be fully bioequivalent. Comparison with in vitro studies concluded that the general test on enteric-coated tablets according to Ph.Eur. did not detect any difference between the four products. A modified dissolution test without mechanical stress gave an indication on differences in the lag time of the different products. 

Two tablet formulations containing crystalline drug substance and 35 % amorphous solid dispersion were evaluated in humans. The results show substantial enhancement (1.7 fold) in the bioavailability of the drug and improved PK variability (Coefficient of Variation (CV) 80 % 18 %) with the tablet made with amorphous solid dispersion (Roche in-house data). The results from this study illustrate the utility of dissolution test conditions that are carefully chosen to simulate physiological conditions (i.e., biorelevant) when applied to testing of a poorly water-soluble weak base and the potential for improved absorption through amorphous formulation technologies. 

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