Marcela Wiater, Dagmara Hoc, Jadwiga Paszkowska, Grzegorz Garbacz

Hydrodynamics and mechanical stresses in pharmacopoeial and noncompendial dissolution testing
2020-06-12

The first and an essential step of medication’s path inside the human body is a dissolution of an active pharmaceutical ingridient. A dissolution of oral dosage forms occurs as a result of physicochemical and mechanical stresses which are found in gastrointestinal tract. This results in dissolution of the API, which becomes ready for the next step - absorption. In recent years, diversity and variability of digestive tract parameters has been understood better due to the advances in the research methods that allowed quantification of forces, mechanical stresses and pH gradients acting therein. Dissolution tests are conducted in order to determine the impact of biorelevant factors on the dosage form. These tests are a basic tool for the preclinical prediction of formulations behaviour in gastrointestinal tract, as well as for the quality control and to ensure formulations invariability after technological alterations in production. Pharmacopeia describes the standard procedure of dissolution tests. However, in the light of the research of actual conditions occurring in gastrointestinal tract the compendial methods appear to not fully reflect the hydrodynamic and mechanical stresses. This results in the lack of discriminatory power of pharmacopoeial dissolution tests, whereas differences between formulations occur in vivo. To face the need, simulators for the whole or partial gastrointestinal tract are constructed. These are advanced devices that enable the determination of the impact of the pH gradient, mechanical stresses and forces, enzymes secretion and many others, on the dosage form. The operation of a number of those simulators successfully predicts the behaviour of medication in vivo, which is an indispensable support during the formulation development. In the article there are described the mechanical and hydrodynamic gastrointestinal stresses, hydrodynamics of the most popular pharmacopoeial apparatus and non compendial gastrointestinal simulators, with regard to their ability to mimic biorelevant hydrodynamics.

Keywords: dissolution, gastrointestinal tract, hydrodynamics, mechanical stress, simulation.

© Farm Pol, 2020, 76 (4): 210–221