Zoomlab™-guided co-crystal engineering of nilotinib for improved dissolution

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery
• Materials Science

Background:

• Nilotinib (NH) is a BCS Class IV drug with poor solubility and permeability, limiting its efficacy for chronic myelogenous leukemia (CML).
• Co-crystallization is a promising strategy to enhance the solubility and dissolution of poorly soluble drugs.

Purpose of the Study:

• To improve nilotinib solubility and dissolution via co-crystallization using computational and experimental methods.
• To develop a stable and effective nilotinib co-crystal formulation for enhanced drug delivery.

Main Methods:

• Utilized BASF's ZoomLab™ platform for rational coformer selection based on solubility parameter difference (Δδv).
• Co-crystallized nilotinib with pyroglutamic acid (PG) using liquid-assisted grinding (LAG).
• Characterized the co-crystal using PXRD, DSC, FTIR, and SEM; assessed solubility, wettability, dissolution, and stability.

Main Results:

• Identified pyroglutamic acid as a suitable coformer with an optimal Δδv threshold of 5 MPa^0.5.
• Confirmed the formation of Nilotinib-Pyroglutamic acid co-crystal (NH-PGCC) with enhanced wettability and a 3.23-fold increase in solubility.
• Achieved 75% drug release in 15 minutes with the optimized NH-PGCC capsule, outperforming marketed formulations, and demonstrated good stability over 6 months.

Conclusions:

• Successfully demonstrated the utility of ZoomLab™ for coformer prediction and formulation development.
• Nilotinib-pyroglutamic acid co-crystal offers a viable approach for enhancing the solubility and dissolution of nilotinib.
• The developed co-crystal formulation shows potential for improved therapeutic outcomes in CML patients.