Polymorphic transformation of antibiotic clarithromycin under acidic condition

Area of Science:

• Pharmaceutical Sciences
• Solid-State Chemistry
• Materials Science

Background:

• Clarithromycin (CAM) is a vital macrolide antibiotic for treating bacterial infections, including Helicobacter pylori.
• Understanding the polymorphic transformations of CAM is crucial for drug formulation and stability.
• The behavior of CAM form II crystals under acidic conditions remains poorly understood.

Purpose of the Study:

• To investigate the polymorphic transformation of Clarithromycin (CAM) form II crystals in acidic environments.
• To elucidate the transformation pathway and kinetics of CAM under varying pH conditions.
• To determine the mechanism of formation for new CAM crystal forms.

Main Methods:

• X-ray powder diffraction was employed to analyze crystal structure changes.
• CAM form II crystals were exposed to hydrochloric acid solutions to induce transformation.
• The Hancock-Sharp equation was utilized to analyze the transformation kinetics and mechanism.

Main Results:

• CAM form II crystals transformed into a gel, then to an unstable form A, and finally to stable form B hydrochloride salts.
• The transformation mechanism for form B was identified as three-dimensional growth of nuclei.
• Transformation rates were quantified, showing that at 37 °C, 95% conversion of form A to form B occurred within 0.69 to 3.79 hours across pH 1.5 to 3.4.

Conclusions:

• The polymorphic transformation of Clarithromycin (CAM) form II to form B via gel and form A is pH-dependent.
• This transformation mechanism suggests potential implications for CAM formulations with prolonged gastric residence time.
• The study provides critical insights into CAM solid-state stability under acidic conditions relevant to gastrointestinal environments.