Polymorphic Conversion of Furosemide after Crystallization in Aqueous Polymeric Solution: Crystallite Analysis Using...

Area of Science:

• Pharmaceutical Sciences
• Materials Science

Background:

• Furosemide (FUR) is a critical loop diuretic with poor water solubility and known polymorphic variations (forms I, II, III, amorphous).
• Controlling polymorphism is essential for improving drug dissolution and bioavailability.

Purpose of the Study:

• To investigate the crystallization of furosemide (FUR) using aqueous polymeric solutions.
• To evaluate the effect of crystallite properties on polymorphic transformation and dissolution rates.

Main Methods:

• Furosemide crystals were prepared using aqueous solutions of HPMC, CMC, MC, or PVA as non-solvents.
• Characterization involved FTIR, XRD, DSC, crystallite size analysis (Scherrer, Williamson-Hall), and in vitro dissolution studies.
• Stability was assessed under accelerated conditions (40 °C/75% RH).

Main Results:

• FTIR, XRD, and DSC confirmed the formation of specific polymorphic forms (Form I and Form II).
• Crystallite size was reduced, dislocation density increased, indicating enhanced structural imperfections.
• All prepared crystals exhibited significantly improved dissolution profiles compared to pure furosemide.
• Stability studies confirmed the retention of respective polymorphic forms under accelerated conditions.

Conclusions:

• Aqueous polymeric solutions are effective for producing stable polymorphic forms of furosemide.
• The crystallization process leads to enhanced dissolution and improved drug properties.