Preparation and characterization of lidocaine HCl-loaded proniosome gels with skin penetration enhancers

Abstract

The present study investigated the effect of incorporating two types of skin penetration enhancers, Transcutol® and d-limonene, in a proniosome gel (PNG) containing 1% w/w lidocaine HCl as a model drug. Different PNG formulations were prepared by coacervation phase separation technique using Span 60®, soy lecithin, cholesterol as the main vesicle ingredients with varying concentrations of Transcutol® (5%, 10%, 20%, 30%) and d-limonene (5%, 10%). The PNGs obtained were light to dark brown semisolid with pseudoplastic flow behavior. The niosomes obtained from the hydration of PNGs showed almost spherical shapes under a scanning electron microscope. The vesicle size, size distribution, zeta potential, and entrapment efficiency (EE) varied depending on the types and concentrations of the enhancers. The in vitro skin permeation and disposition of all PNGs and control formulations were performed on porcine ear skin. The results showed that using 20% Transcutol® in PEG base provided the highest skin permeation flux of lidocaine HCl (81.42 ± 5.00 μg/cm2/h). However, T20 PNGs containing 20% Transcutol® provided the highest skin disposition (419.23 ± 87.52 mg/g skin) which was significantly higher than from 20% Transcutol® in PEG base. Therefore, T20 PNG could be a good carrier for enhancing the drug disposition in the skin. An inverse relationship was observed between the flux and EE of each PNG (R2 0.7749). The results indicate that the optimal concentration of Transcutol® and its effect on EE could contribute to the flux of lidocaine HCl across the skin. The skin permeation enhancing effect of hydrated T20 niosome was investigated. It could enhance lidocaine HCl permeation at a higher penetration-enhancement ratio (ER) than its precursor PNG (ER 4.25 ± 0.54 vs 1.45 ± 0.13-fold compared with PEG base), indicating the effect of its niosome form which facilitated the skin permeation of lidocaine HCl. Furthermore, T20 PNG exhibited good stability after storage at room temperature for three months. The results suggested that the types and concentrations of the penetration enhancers in PNGs could affect their niosomal characteristics and skin penetration-enhancing effect. Thus, these should be carefully considered in formulation development.