Baicalein-nicotinamide cocrystal with enhanced solubility, dissolution, and oral bioavailability

Area of Science:

• Pharmaceutical Science
• Drug Delivery
• Materials Science

Background:

• Baicalein (BE) is a promising natural compound with therapeutic potential.
• Poor solubility and low oral bioavailability limit the clinical application of BE.
• Cocrystallization is a strategy to improve drug properties.

Purpose of the Study:

• To investigate the effect of preparation methods on baicalein-nicotinamide (BE-NCT) cocrystal formation.
• To analyze the intermolecular interactions within the BE-NCT cocrystal.
• To demonstrate the simultaneous enhancement of solubility, dissolution, and oral bioavailability of BE via cocrystallization.

Main Methods:

• Cocrystallization of baicalein (BE) and nicotinamide (NCT) using three different preparation methods.
• Characterization of cocrystals using differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD).
• In vitro assessment of solubility and dissolution rates.
• In vivo pharmacokinetic studies in rats to evaluate oral bioavailability (Cmax and AUC).

Main Results:

• Three preparation methods yielded BE-NCT cocrystals with similar DSC thermograms and XRPD patterns.
• BE-NCT cocrystal exhibited significantly improved solubility and dissolution compared to crystalline BE.
• BE-NCT cocrystal demonstrated a 2.49-fold higher Cmax and 2.80-fold higher AUC in rats.
• The oral bioavailability enhancement by BE-NCT cocrystal surpassed that of previously reported BE nanocrystals.

Conclusions:

• BE-NCT cocrystallization effectively enhances the solubility, dissolution, and oral bioavailability of baicalein.
• The developed BE-NCT cocrystal offers a promising approach for improving BE's therapeutic efficacy.
• This study provides foundational knowledge for the future development of baicalein into efficacious drug products.