Solid dispersions containing ursolic acid in Poloxamer 407 and PEG 6000: A comparative study of fusion and solvent methods

• Solvent and fusion methods produced solid dispersions of ursolic acid in PEG 6000 and Poloxamer 407.
• Drugs in solid dispersions by the solvent method were converted from a crystalline to amorphous form.
• Hydrogen bolding between drug and carriers could be detected for solid dispersions by the solvent method.
• Fusion method caused polymorphic change in ursolic acid.
• Solid dispersions with Poloxamer 407 by the solvent method improved solubility and dissolution rate of ursolic acid.

Ursolic acid is a molecule with several therapeutic applications not yet commercially explored because of its bioavailability-limiting water insolubility. To avoid this drawback, solid dispersions containing ursolic acid have been employed to increase water solubility. The influence of hydrophilic carriers, PEG 6000 and Poloxamer 407, and the method of preparation, fusion and solvent, were studied for ursolic acid in this work. The solid dispersions and physical mixtures were characterized by particle size, scanning electron microscopy, fourier transform infrared spectroscopy, X-ray diffractometry, differential scanning calorimetry, hot stage microscopy, water solubility and dissolution profile. Results showed that both methods and polymers used for solid dispersion preparation resulted in homogeneous powders, but the surfactant Poloxamer 407 enhanced the ursolic acid solubility in solid dispersions better than PEG 6000. With Poloxamer 407, both methods enabled complete dissolution of ursolic acid in phosphate buffer; however the solid dispersion showed higher solubility when prepared by the solvent method compared to the fusion method, 689.47 μg/mL and 328.52 μg/mL, respectively. For comparison, the physical mixture solubility was 248.17 μg/mL. The better results achieved with the solvent method were attributed to smaller particle size, amorphic conversion of ursolic acid from its less soluble crystalline state and hydrogen bond formation between drug and carrier, whereas there was a polymorphic change caused by the fusion method. Results indicated that the solid dispersion prepared by the solvent method is an adequate approach to increasing ursolic acid solubility and dissolution, a very important step toward the development of a pharmaceutical dosage form containing ursolic acid.

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