A novel microdialysis-dissolution/permeation system for testing oral dosage forms: A proof-of-concept study

Area of Science:

• Biopharmaceutical Sciences
• Drug Delivery Systems
• Analytical Chemistry

Background:

• Accurate assessment of oral drug formulations requires understanding both dissolution and permeation kinetics.
• Conventional methods for sampling drug concentrations can disturb the process and lack temporal resolution.
• Distinguishing between molecularly dissolved and apparently dissolved drug species is crucial for biopharmaceutical evaluation.

Purpose of the Study:

• To develop and validate a novel microdialysis-dissolution/permeation (M-D/P) system for biopharmaceutical assessment of oral drug formulations.
• To simultaneously quantify dissolution and permeation kinetics under physiologically relevant conditions.
• To demonstrate the advantages of the M-D/P system over conventional direct sampling methods.

Main Methods:

• Development of a microdialysis-dissolution/permeation (M-D/P) system integrating a diffusion chamber, microdialysis unit, and biomimetic Permeapad®.
• Utilizing hydrocortisone (HCS) as a model drug and buffer/fasted state simulated intestinal fluids (FaSSIF) as dissolution media.
• Simultaneous measurement of molecularly dissolved drug in the dissolution compartment and permeated drug in the acceptor compartment over time.

Main Results:

• The M-D/P system successfully profiled dissolution and permeation of hydrocortisone in both buffer and FaSSIF.
• The M-D/P system sampling showed minimal disturbance to the permeation process.
• The system effectively differentiated molecularly dissolved from apparently dissolved hydrocortisone in FaSSIF, offering advantages in labor and temporal resolution over conventional methods.

Conclusions:

• The novel M-D/P system is a promising tool for biopharmaceutical assessment of oral drug formulations.
• It provides a simple, routine method for researchers to comprehend the interplay between dissolution and permeation.
• This system aids in improved oral formulation screening and ultimate dosage form assessment.