Physicochemical characterization, solubilization, and stabilization of 9-nitrocamptothecin using pluronic block...

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Physical Chemistry

Background:

• 9-nitrocamptothecin (9NC) exhibits poor aqueous solubility and hydrolytic instability, limiting its therapeutic efficacy.
• Understanding the solid-state properties and physicochemical characteristics of 9NC is crucial for developing effective drug delivery systems.

Purpose of the Study:

• To investigate the solid-state properties and physicochemical characteristics of 9-nitrocamptothecin (9NC).
• To understand the molecular and bulk level factors contributing to 9NC's poor aqueous solubility and hydrolytic instability.
• To evaluate the potential of pluronic copolymers in enhancing 9NC solubility and stability.

Main Methods:

• Characterization of 9NC bulk drug substance, including morphology and melting point.
• Assessment of 9NC hydrolysis across a range of pH values.
• Solubility studies of 9NC in deionized water and acidic media.
• Evaluation of pluronic copolymers (P123, F127, F68) for enhancing 9NC solubility.
• Thermodynamic stability assessment of drug-loaded pluronic micelles.

Main Results:

• 9NC is a nonhygroscopic crystalline solid with a melting point of 264°C.
• 9NC hydrolysis occurs above pH 4, with complete conversion to carboxylate above pH 8.
• Total 9NC solubility in deionized water is <5 μg/mL; in acidic media, it's ~2.5 μg/mL.
• Pluronic copolymers P123, F127, and F68 increased 9NC solubility by 13-, 8-, and 5-fold, respectively.
• Pluronic F127 demonstrated the highest hydrolytic protection efficacy for 9NC.

Conclusions:

• Pluronic copolymers significantly enhance the aqueous solubility of 9-nitrocamptothecin.
• Pluronic F127 offers superior hydrolytic protection for 9NC, suggesting its potential for improved drug delivery formulations.
• Further research into pluronic-based 9NC formulations could overcome existing delivery challenges.