Mechanistic Basis of Cocrystal Dissolution Advantage.

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Physical Chemistry

Background:

• Cocrystal development is driven by potential improvements in drug solubility and dissolution rates.
• Carbamazepine (CBZ) and its cocrystals (CBZ-SAC, CBZ-SLC) are investigated for their dissolution behaviors.
• Understanding dissolution mechanisms is crucial for optimizing drug delivery.

Purpose of the Study:

• To mechanistically analyze and compare the dissolution of carbamazepine and its cocrystals.
• To derive a mathematical model describing the dissolution advantage of cocrystals.
• To investigate the influence of pH and micellar solubilization on dissolution.

Main Methods:

• Mass transport analyses were employed to study dissolution.
• A mathematical equation was derived to quantify the dissolution advantage.
• Effective diffusivity of carbamazepine and its cocrystals was measured under varying conditions.

Main Results:

• The dissolution advantage of cocrystals was defined as the product of solubility and diffusivity advantages.
• Effective diffusivity of carbamazepine was found to be lower than its cocrystals in the presence of surfactants.
• Cocrystals can exhibit a dissolution advantage and thermodynamic stability under specific conditions.

Conclusions:

• Cocrystal dissolution advantage is influenced by both solubility and diffusivity.
• Improved drug diffusivity from dissolved cocrystals can enhance dissolution, even for less soluble cocrystals.
• Mass transport models provide valuable insights for cocrystal selection and formulation development.