Physicochemical characterization of spray-dried phenylbutazone polymorphs

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Physical Chemistry

Background:

• Phenylbutazone exhibits polymorphism, impacting its dissolution and bioavailability.
• Traditional recrystallization methods have limitations in accessing all polymorphic forms.

Purpose of the Study:

• To investigate spray-drying as a method for phenylbutazone recrystallization.
• To characterize novel crystalline forms of phenylbutazone, particularly form epsilon.
• To evaluate the dissolution properties of different phenylbutazone polymorphs.

Main Methods:

• Spray-drying of phenylbutazone from methylene chloride solution.
• Characterization using X-ray powder diffractometry, differential thermal analysis, IR spectrophotometry, scanning electron microscopy, and hot-stage photomicroscopy.
• Dissolution testing in simulated intestinal fluid.

Main Results:

• Three crystalline forms (delta, beta, epsilon) were prepared by varying spray-drying temperatures.
• Form epsilon, a novel polymorph, was successfully synthesized, which is unobtainable via recrystallization.
• Form epsilon demonstrated significantly higher solubility and excellent in vitro availability compared to other forms.

Conclusions:

• Spray-drying is an effective technique for controlling phenylbutazone polymorphism.
• The novel epsilon polymorph offers superior dissolution properties, potentially enhancing therapeutic efficacy.
• Drying temperature in spray-drying critically influences the resulting crystalline form and its properties.