Establishing experimental parameters for biphasic transfer in vitro lipolysis model

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery
• Biopharmaceutics

Background:

• Lipid-based formulations (LBFs) enhance oral drug bioavailability but standard in vitro lipolysis assays have limitations.
• Existing assays lack absorptive sinks and dynamic pH changes, reducing predictive accuracy for in vivo performance.
• Simulating gastrointestinal transit is crucial for understanding drug release from LBFs.

Purpose of the Study:

• To develop a biphasic in vitro lipolysis model that incorporates an absorptive sink.
• To simulate dynamic gastrointestinal transit using pH-transition approaches.
• To enhance the predictive power of in vitro digestion models for LBF performance.

Main Methods:

• Developed a biphasic model with a decanol layer as an absorptive sink.
• Employed two dynamic pH-transition methods: biphasic GI-transfer and biphasic pH-shift.
• Utilized nilotinib-loaded LBFs to test the model, assessing media composition and lipase effects.

Main Results:

• Digestion with porcine pancreatin or Palatase increased nilotinib in the aqueous phase, reducing partitioning into the decanol sink.
• A readily dispersible LBF showed decreased nilotinib permeation in the GI-transfer model due to better solubilization.
• A poorly dispersible LBF performed better in the pH-shift model, with higher drug levels in the decanol layer.

Conclusions:

• Established conditions for evaluating LBF lipolysis during dynamic pH transitions with an absorptive sink.
• The advanced model offers insights into digestion- and pH-mediated supersaturation during LBF digestion.
• This model has the potential to increase the predictive relevance of in vitro digestion assays for LBFs.