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The formulation developments and the in vivo assessment of Biopharmaceutical Classification System (BCS) class II drugs are challenging due to their low solubility and high permeability in the human gastrointestinal (GI) tract. Since the pH change in the GI environment influences the drug dissolution of BCS class IIa and IIb drugs but not for IIc drugs, the incorporation of the human GI characteristics into the in vitro dissolution system may not be crucial for BCS class IIc drugs to predict their bioperformance. An absorptive compartment in dissolution apparatus would be important to predict bioperformance of BCS class IIc drugs due to their physicochemical characteristics, low solubility and high permeability. In this study, an absorptive compartment (biphasic system) was introduced to a gastrointestinal simulator (GIS) and USP dissolution apparatus II for the evaluation of in vivo prediction for BCS class IIc drugs. Those in vitro systems with the biphasic phase were evaluated for the prediction of in vivo dissolution of BCS class IIc drugs, donepezil and danazol, and subsequent absorption. For the evaluation of in vivo dissolution of BCS class IIc drugs, simpler dissolution apparatus, USP II, with the absorptive phase might be adequate a dissolution method to predict in vivo.

The “3rd International Symposium on BA/BE of Oral Drug Products – Biopharmaceutics meets Galenics (BA/BE 2018)” was held during 11–12th of October 2018 at INFARMED, the Portuguese regulatory medicines agency, in Lisbon, Portugal. Summary of this meeting and perspective/directions of biopharmaceutical researches are discussed in this opinion paper.

The discovery pipelines in pharmaceutical companies are highly populated with poorly soluble compounds, demanding for an appropriate solution to overcome this problem. Generating supersaturated concentrations for these drugs in the gastrointestinal (GI) tract has been put forward as a promising strategy to assure sufficient systemic exposure after oral intake of the drug. Numerous publications have shown to which extent supersaturating dosage forms can create supersaturated concentrations by testing these formulations in in vitro dissolution models. The obtained dissolution profiles can serve as a valuable input for computational software programs to simulate the systemic outcome of the drug. To improve our fundamental knowledge and understanding of the impact of supersaturation/precipitation on oral absorption, attempts have been made to develop biopredictive in vitro dissolution systems such as the Gastrointestinal Simulator (GIS), the dissolution/permeation system, and the biphasic test system. Moreover, aspiration studies in humans have been performed throughout the years to measure simultaneously GI and systemic concentrations of the drug in order to directly envisage the impact of supersaturation on systemic exposure. This manuscript aims to provide a comprehensive review with respect to the predictive power of in vitro tools towards the in vivo performance of supersaturating dosage forms. Different case studies will be thoroughly presented where a plethora of supersaturating formulations was tested applying a biopredictive setting. Recent investigations on liquid-liquid phase separation of supersaturated solutions, which makes comprehension of the dissolution process of supersaturating dosage forms extremely challenging, are also discussed.