A stable hydrocortisone nanosuspension for improved dissolution: Preparation, characterization and in vitro...

Area of Science:

• Pharmaceutical Sciences
• Materials Science

Background:

• Drug nanosuspensions are increasingly utilized for drug delivery.
• Hydrocortisone, a water-insoluble drug, presents challenges in achieving therapeutic concentrations.
• Enhancing solubility and dissolution is crucial for improving the efficacy of poorly soluble drugs.

Purpose of the Study:

• To prepare a hydrocortisone nanosuspension using wet milling.
• To evaluate the impact of nanonization on hydrocortisone's solubility, dissolution rate, and bioavailability.
• To assess the physical stability of the hydrocortisone nanosuspension.

Main Methods:

• Wet milling technique was employed to create hydrocortisone nanosuspensions.
• Particle size, zeta potential, and particle shape were characterized.
• Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) were used to analyze crystallinity.
• Solubility, dissolution rate, and in vivo bioavailability (AUC 0-9h) were determined.
• Physical stability was assessed at room temperature over 24 months.

Main Results:

• Hydrocortisone nanosuspensions exhibited a particle size of 290 nm ± 9 nm with a narrow particle size distribution (PDI = 0.17).
• Solubility of hydrocortisone increased by approximately 2.9-fold (875µg/ml ± 2.5) after nanonization.
• Dissolution rate was substantially enhanced, with >97% dissolved within 10 minutes compared to raw hydrocortisone (22.3%) and commercial tablets (50%).
• In vivo studies showed a significantly higher AUC 0-9h for hydrocortisone nanosuspensions (31.50±2.50) compared to hydrocortisone solution (14.85±3.25).
• The nanosuspension demonstrated physical stability at room temperature for 24 months.

Conclusions:

• Wet milling is an effective method for producing hydrocortisone nanosuspensions with improved physicochemical properties.
• Nanonization significantly enhances the saturation solubility and dissolution rate of hydrocortisone.
• The developed hydrocortisone nanosuspension formulation leads to improved bioavailability and exhibits good physical stability.