Crystallinity and dissolution rate of tolbutamide solid dispersions prepared by the melt method

Area of Science:

• Pharmaceutical Sciences
• Materials Science

Background:

• Solid dispersions enhance drug solubility and bioavailability.
• Melt method is a common technique for preparing solid dispersions.
• Cooling rate can influence the physical state of drug-carrier systems.

Purpose of the Study:

• To investigate the effect of cooling rate on solid dispersions prepared by the melt method.
• To characterize the solid-state properties of tolbutamide-urea and tolbutamide-polyethylene glycol 6000 dispersions.
• To determine the optimal conditions for forming amorphous solid dispersions.

Main Methods:

• Preparation of solid dispersions using the melt method.
• Varying cooling rates (rapid vs. slow) during dispersion preparation.
• Characterization using X-ray diffraction (XRD) and scanning electron microscopy (SEM).

Main Results:

• Slow-cooled tolbutamide-urea dispersions showed no crystallinity, indicating amorphous solid formation.
• Rapidly cooled tolbutamide-urea dispersions exhibited urea crystallinity and no drug peaks in XRD, suggesting molecular dispersion.
• Both rapid and slow cooling of tolbutamide-polyethylene glycol 6000 dispersions resulted in physical mixtures, as shown by XRD.

Conclusions:

• Cooling rate significantly influences the solid-state properties of tolbutamide-urea solid dispersions.
• Urea is a suitable carrier for forming amorphous tolbutamide via the melt method with controlled cooling.
• Polyethylene glycol 6000 did not facilitate amorphous solid dispersion formation with tolbutamide under the studied conditions.