Using biorelevant dissolution to obtain IVIVC of solid dosage forms containing a poorly-soluble model compound

Area of Science:

• Pharmacokinetics and Drug Development
• Biopharmaceutical Sciences
• Formulation Science

Background:

• Predicting in vivo drug absorption from in vitro dissolution is crucial for drug development.
• Poorly soluble compounds present challenges in achieving reliable dissolution profiles.
• Biorelevant dissolution media (BDM) aim to mimic physiological conditions.

Purpose of the Study:

• To evaluate the utility of selected biorelevant dissolution media (BDM) in predicting in vivo drug absorption.
• To compare dissolution profiles in various BDM simulating fasted and fed states.
• To establish an in vitro-in vivo correlation (IVIVC) for drug absorption.

Main Methods:

• Dissolution profiles of a poorly soluble model compound in different BDM were analyzed.
• An in vivo dog study was conducted to obtain plasma absorption data.
• Non-linear regression software was used to develop IVIVC models.

Main Results:

• All tested media differentiated between formulations, with formulation A performing best.
• Fed state BDM (BDM 3) with high bile salt (BS) and lipolysis product (LP) levels showed the best prediction.
• IVIVC models achieved prediction errors below 10% for Cmax and AUC.

Conclusions:

• Appropriate selection and use of biorelevant dissolution media are critical for accurate in vitro-in vivo correlation.
• Physiologically relevant media containing BS and LP show significant potential for formulation and early drug development.
• This study highlights the importance of BDM in predicting drug absorption and optimizing formulation strategies.