Biorelevant dissolution testing and physiologically based absorption modeling to predict in vivo performance of supersaturating drug delivery systems

Supersaturating drug delivery systems (SDDS) enhance the oral absorption of poorly water-soluble drugs by achieving a supersaturated state in the gastrointestinal tract. The maintenance of a supersaturated state is decided by the complex interplay among inherent properties of drug, excipients and physiological conditions of gastrointestinal tract. The biopharmaceutical advantage through SDDS can be mechanistically investigated by coupling biopredictive dissolution testing with physiologically based absorption modeling (PBAM).

However, the development of biopredictive dissolution methods possess challenges due to concurrent dissolution, supersaturation, precipitation, and possible redissolution of precipitates during gastrointestinal transit of SDDS. In this comprehensive review, our effort is to critically assess the current state-of-knowledge and provide future directions for PBAM of SDDS. The review outlines various methods used to retrieve physiologically relevant values for input parameters like solubility, dissolution, precipitation, lipid-digestion and permeability of SDDS. SDDS-specific parameterization includes solubility values corresponding to apparent physical form, dissolution in physiologically relevant volumes with biorelevant media, and transfer experiments to incorporate precipitation kinetics.

Interestingly, the lack of experimental permeability values and modification of absorption flux through SDDS possess the additional challenge for its PBAM. Supersaturation triggered permeability modifications are reported to fit the observed plasma concentration-time profile. Hence, the experimental insights on good fitting with modified permeability can be potential area of future research for the development of in vitro methods to reliably predict oral absorption of SDDS.

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Article information: Samarth D Thakore, Arvind Sirvi, Vikram C Joshi, Sanjali S Panigrahi, Arijita Manna, Ridhima Singh, Abhay T Sangamwar, Arvind K Bansal, Biorelevant dissolution testing and physiologically based absorption modeling to predict in vivo performance of supersaturating drug delivery systems, International Journal of Pharmaceutics, Volume 607, 2021. https://doi.org/10.1016/j.ijpharm.2021.120958.