Relative Bioavailability Assessment of Solid Forms by An Artificial Stomach and Duodenum Apparatus

Area of Science:

• Pharmacokinetics and Drug Metabolism
• Materials Science and Engineering
• Pharmaceutical Sciences

Background:

• Predicting oral drug bioavailability is crucial for pharmaceutical development.
• Solid-state properties significantly influence the bioavailability of poorly soluble compounds.
• The artificial stomach and duodenum (ASD) model offers a potential in vitro method for assessing drug performance.

Purpose of the Study:

• To evaluate the predictive capability of the artificial stomach and duodenum (ASD) model for in vivo bioavailability.
• To investigate the influence of different solid forms of a poorly soluble compound (BI-639667) on its bioavailability.
• To assess the correlation between in vitro dissolution profiles and in vivo outcomes.

Main Methods:

• Tested a poorly soluble compound, BI-639667, in solution and four different solid forms (suspensions).
• Evaluated dissolution performance using the artificial stomach and duodenum (ASD) apparatus.
• Determined in vivo bioavailability of BI-639667 in rats for comparison.
• Correlated in vitro dissolution data with in vivo bioavailability results.

Main Results:

• The rank order of bioavailability predicted by the ASD model closely matched the in vivo results in rats.
• The observed bioavailability order was: solution > salicylic acid cocrystal > malate salt > maleate salt > monohydrate.
• The ability of solid forms to maintain supersaturation correlated with bioavailability, highlighting the importance of dissolution performance.

Conclusions:

• The artificial stomach and duodenum (ASD) model demonstrates strong predictive power for in vivo drug bioavailability.
• ASD testing is a valuable tool for characterizing the dissolution performance of different solid forms.
• Utilizing the ASD model can aid in the rational selection of solid forms during tablet formulation development.