Enhanced transdermal permeation and anti-inflammatory potential of phospholipids complex-loaded matrix film of umbelliferone: Formulation development, physico-chemical and functional characterization

Eur J Pharm Sci. 2019 Apr 1:131:23-38. doi: 10.1016/j.ejps.2019.02.006. Epub 2019 Feb 5.

Abstract

In the present study, umbelliferone - phospholipids complex - loaded matrix film (UPLC - MF) was developed with a goal of improving transdermal permeation and anti-inflammatory potential of umbelliferone (UMB). Umbelliferone - phospholipids complex (UPLC) was prepared using solvent evaporation method. UPLC-MF was prepared by simple and reproducible solvent casting method. Prepared UPLC and UPLC-MF were both physico-chemically characterized by Fourier transforms infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), powder x-ray diffraction (PXRD), proton nuclear magnetic resonance spectroscopy (1H NMR), weight variation, thickness, tensile strength, folding endurance, % elongation, moisture content and uptake Functional characterization of UPLC and UPLC-MF was carried out by solubility analysis, in vitro dissolution, diffusion, and ex vivo permeation via dialysis and biological membrane. UPLC - MF was also evaluated for in vivo anti-inflammatory activity using carrageenan-induced Albino rat paw model. Design-based optimal values for formulation and process variables of UPLC were observed to be 1:1.78, 50 °C and 2 h, respectively. Physico-chemical characterization confirmed the formation of the complex and the film. UPLC demonstrated a higher aqueous solubility (~11-fold), compared to pure UMB. Rate and extent of dissolution of UMB from UPLC was enhanced significantly to that of pure UMB. Compared to UMB-MF, the diffusion and permeation rate of UMB from UPLC-MF enhanced significantly. The UPLC - MF improved the anti-inflammatory potential of UMB by significant enhancement of edema inhibition (%), compared to UMB-MF. The obtained results showed that the present combined formulation system could be employed as a promising strategy for improving transdermal permeation of UMB.

Keywords: In vivo anti-inflammatory potential; Phospholipids; Solubility; Transdermal permeation; Umbelliferone.

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Anti-Inflammatory Agents / chemistry
  • Drug Carriers / administration & dosage*
  • Drug Carriers / chemistry
  • Drug Compounding
  • Drug Liberation
  • Edema / drug therapy
  • Female
  • Male
  • Phospholipids / administration & dosage*
  • Phospholipids / chemistry
  • Rats, Hairless
  • Rats, Wistar
  • Skin / metabolism
  • Skin Absorption*
  • Solubility
  • Umbelliferones / administration & dosage*
  • Umbelliferones / chemistry

Substances

  • Anti-Inflammatory Agents
  • Drug Carriers
  • Phospholipids
  • Umbelliferones