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

Pak J Pharm Sci. 2017 Sep;30(5):1635-1643.

Abstract

Drug nanosuspensions have gained tremendous attraction as a platform in drug delivery. In the present work, a nanosuspension was prepared by a wet milling approach in order to increase saturation solubility and dissolution of the water insoluble drug, hydrocortisone. Size of the generated particeles was 290 nm ± 9 nm having a zeta potential of -1.9 mV ± 0.6 mV. Nanosized particles were found to have a rod shape with a narrow particle size distribution (PDI =0.17). Results of differential scanning calorimetry and X-ray diffraction analyses revealed minor modifications of crystallinity of hydrocortisone following the milling process. Solubility of hydrocortisone was enhanced by nanonization to 875µg/ml ±2.5, an almost 2.9-fold compared to the raw hydrocortisone. Moreover, the nanosuspension formulation substabtially enhanced the dissolution rate of hydrocortisone where >97% of the hydrocortisone was dissolved within 10 minutes opposed to 22.3% for the raw 50% for the raw hydrocortisone and the commercial tablet, respectively. The bioavailability study resulted in AUC 0-9h for HC nanosuspensions (31.50±2.50), which is significantly (p<0.05) higher compared to the AUC 0-9h (14.85±3.25) resulted for HC solution. The nanosuspension was physically stable at room temperature for 24 months.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Biological Availability
  • Calorimetry, Differential Scanning
  • Crystallography, X-Ray
  • Drug Compounding
  • Drug Liberation
  • Drug Stability
  • Hydrocortisone / administration & dosage
  • Hydrocortisone / chemistry*
  • Hydrocortisone / pharmacokinetics
  • Injections, Intraocular
  • Male
  • Microscopy, Electron, Scanning
  • Microscopy, Electron, Transmission
  • Nanoparticles*
  • Nanotechnology
  • Pharmaceutical Solutions
  • Rabbits
  • Solubility
  • Technology, Pharmaceutical / methods

Substances

  • Pharmaceutical Solutions
  • Hydrocortisone