Dr M. AI-Saket, Jordan

The Drug Directorate at the Ministry of Health in Jordan is aware of the importance of bioequivalence studies as an essential requirement for drug registration to increase trade and the number of locally produced drugs. In 1986, the Drug Directorate adopted a policy of requesting bioequivalence studies for the following categories: sustained release products, enteric coated products, and low dissolution profile products.

In 1998, the Drug Directorate began implementation of regulations as a prerequisite to drug registration. The therapeutic efficacy of pharmaceutical formulations is governed by factors related to both the in vitro dissolution characteristics of the drug, and its in vivo bioavailablity. This inherent interdependency within the drug-patient biosystem is the major concern underlying the importance of in vitro/in vivo correlation studies.

The dissolution rate of a specific dosage form is essentially an arbitrary parameter that is very dependent on the methodology utilized in generating data. Changes in the type of apparatus, dissolution medium, agitation speed, etc., can modify dramatically the dissolution pattern. Therefore, unless it is demonstrated experimentally that the in vitro dissolution behaviour reflects the in vivo performance in humans, the data can be of no relevant value in predicting or passing any judgement on the clinical effectiveness of a drug product. In other words, the bioavailability implications of dissolution should never be accepted on faith; rather they must be proven through carefully designed in vitro/in vivo correlation studies.

Dissolution tests are usually used for the development of a new product, to assist with the determination of bioequivalence, and to assist in choosing a formulation. They may also serve to evaluate whether more clinical studies are needed to assess product bioavailabilty when no correlation exists. In general, it has been noted that for immediate release dosage forms a good level of correlation has been reported and the dissolution profiles were predictive of human bioavailability in many cases. For sustained release dosage forms the problem is much more complex.

In summary, there is a real need to develop dissolution tests that better predict in vivo performance of drug products. This could be achieved if the conditions in the gastrointestinal tract were successfully reconstructed in in vitro systems. The development of prognostic in vitro tests should lead not only to a reduction in the work needed for formulation development, but also in the number and size of clinical studies required, as well as to more meaningful quality assurance tests.