Development of eplerenone nano sono-crystals using factorial design: enhanced solubility and dissolution rate via anti solvent crystallization technique

Abstract

Objective

The purpose of this work was to improve EP solubility by using a sono-crystalization approach to reduce particle size and hence, increase the dissolution rate. Significance Eplerenone (EP) is an antagonist of the aldosterone receptor and is used for the treatment of hypertension and chronic heart failure. EP was classed as biopharmaceutical classification (BCS) class II because of its poor solubility and high permeability, which retards dissolution rate and drug absorption, and decreases bioavailability.

Methods

Three-factors and two-level (2³) multifactorial design have been employed to study the effect of independent variables which are drug concentration; (X1), stabilizer type (X2), and stabilizer concentration (X3) on responses; saturated solubility of EP in distilled water (Y1), saturated solubility in acidic media pH 1.2 (Y2), particle size (Y3), and polydispersity index, PDI (Y4). Also, they were characterized by Fourier transformed infrared spectroscopy (FTIR), Powder X-ray diffraction (PXRD), Differential scanning calorimetry (DSC), and yield percentage. The optimum formula was further subjected to an in-vitro release study.

Results

The optimized formulation showed a saturated solubility of EP as 1.29, and 1.86 (mg/ml) in distilled water and acidic media (pH 1.2) respectively. Also, the particle size of 133 nm, and PDI of 0.824 with a small percentage of the difference between the observed and predicted values. Ninety-one percent of EP was released within 10 min., and it was completely released within 45 min. with a significantly higher release rate compared to raw drug.

Conclusion

This work resulted in a satisfactory enhancement of solubility and dissolution rate which, is suitable for further in-vivo analysis.

Graphical Abstract

Keywords:

• Eplerenone
• sono-crystalization
• antisolvent technique
• dissolution rate
• full factorial design

Acknowledgment

The authors gratefully thank October University for Modern Sciences and Arts for the great support during carrying out this research work.

Author contributions

All authors contributed equally to the experimental phase, and during writing the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study got no support from any government, commercial, or nonprofit organization.