Exploring the co-loading of lidocaine chemical forms in surfactant/phospholipid vesicles for improved skin delivery

J Pharm Pharmacol. 2015 Jul;67(7):909-17. doi: 10.1111/jphp.12385. Epub 2015 Feb 3.

Abstract

Objectives: The present study was aimed at targeting the skin to deliver lidocaine loaded in surfactant/phospholipid vesicles tailored for improved local delivery. The influence of different formulation parameters was explored to maximise drug efficacy.

Methods: The vesicles were prepared using a mixture of soy lipids (Phospholipon 50) and a surfactant with penetration-enhancing properties (Oramix CG110, Labrasol, Labrafac PG or Labrafac CC), and loaded with lidocaine. The formulations were analysed in detail by cryo-TEM, SAXS, Turbiscan Lab, and tested in permeation experiments through new born pig skin, as a function of the chemical form and concentration of lidocaine (i.e. free base or salt, 12.5 or 25 mg/ml).

Key findings: Small, spherical vesicles with good entrapment efficiency and exceptional long-term stability were produced. The lamellar organisation was affected by either the surfactant or the lidocaine form used. Permeation studies highlighted that the co-incorporation of lidocaine base + hydrochloride allowed the achievement of a superior deposition in the skin layers, especially when surfactant vesicles were used, as their content was presumably saturated with the maximum amount of loadable anaesthetic.

Conclusions: The proposed systems based on surfactant/phospholipid vesicles co-loaded with both lidocaine forms are an effective approach for improving its local delivery.

Keywords: accelerated stability; lamellar structure; lidocaine; skin delivery; surfactant/phospholipid vesicle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Chemistry, Pharmaceutical / methods
  • Drug Carriers / administration & dosage
  • Drug Carriers / chemistry
  • Drug Stability
  • Glycerides / administration & dosage
  • Glycerides / chemistry
  • Lidocaine / administration & dosage*
  • Lidocaine / chemistry*
  • Permeability
  • Phospholipids / administration & dosage*
  • Phospholipids / chemistry*
  • Skin / metabolism*
  • Skin Absorption / physiology
  • Surface-Active Agents / administration & dosage*
  • Surface-Active Agents / chemistry*
  • Swine

Substances

  • Drug Carriers
  • Glycerides
  • Phospholipids
  • Surface-Active Agents
  • Labrasol
  • Lidocaine