In order to achieve an adequate estimate of in vivo release behavior for solid dosage forms, the relevant physiological conditions, in addition to the physico-chemical properties of a drug substance and its formulation, should be taken into serious consideration during the development of a biorelevant dissolution testing system. Specifically, the biorelevant dissolution method should be able to simulate the in vivo environment where the majority of the drug is released from the formulation. In principle, the design of such a system should, at minimum, account for the following factors to reflect the physiological conditions in the GI tract:
1. pH Conditions
2. Key aspects of the composition of the GI contents (e.g., osmolarity, ionic strength, surface tension, bile salts, and phospholipids)
3. Volume of the GI contents
4. Transit times
5. Motility pattern
6. Dosing conditions (e.g., administered with food)
To reflect the effect of these factors on the drug release, it is important to utilize the dissolution media that mimic the conditions in the GI tract and the apparatus that can simulate the dynamic environment that the dosage form experiences in the GI tract. Thus, in comparison to dissolution methods used for QC, which at best simulate pH effects and/or osmolality on the drug release under in vivo conditions, biorelevant dissolution media are generally more complex and are often not suitable for the purpose of QC.
Prior to the discussion of biorelevant dissolution methods, it is important to first review the concept and application of the in vitro-in vivo correlation and the importance of the BCS on the biorelevant dissolution testing development. The biorelevant dissolution media, apparatus and test conditions will be discussed with emphasis on their relevance to the physiological factors, including the pH, composition of the GI fluids, volume, GI hydrodynamics/motility, and food effect. The remaining challenges regarding the future development of biorelevant dissolution testing will also be highlighted.
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