Biocompatible lidocaine and prilocaine loaded-nanoemulsion system for enhanced percutaneous absorption: QbD-based optimisation, dermatokinetics and in vivo evaluation

Abstract

Barrier properties of the skin and physicochemical properties of the drugs are the main hiccups in delivering local anaesthetic molecules topically. The present work endeavours for systematic optimisation and evaluation of nanoemulsions (NEs) of local anaesthetic drugs, lidocaine and prilocaine, employing the systematic approach of Quality by Design. A 3³ Box–Behnken design was employed for systematic optimisation of the factors obtained from screening studies employing Plackett–Burman design and risk assessment studies. The superior permeation rates, and higher concentrations of the drugs in skin layers from the optimised NE carriers, were achieved in permeation and dermatokinetic studies, when compared to marketed cream. Furthermore, rapid onset of action was demonstrated by the NE system in rabbit eye corneal reflex model and biocompatibility was confirmed from the absence of any marked skin change(s) in the normal skin histology. The developed NE systems demonstrated it as a promising carrier for topical delivery of lidocaine and prilocaine.

• Dermatokinetic modelling
• formulation by design
• local anaesthetic
• phospholipid
• skin bioavailability
• submicron emulsion
• transdermal

Acknowledgements

The authors are thankful to M/s IPCA Labs Ltd. Ratlam, India for generously providing the gift samples of lidocaine and prilocaine, while to M/s BASF, Germany and M/s Phospholipid GmbH, Nattermannallee, Germany, for the ex gratis supply of poloxamer 407 and phospholipids, respectively.

Declaration of interest

Financial grants obtained from University Grants Commission (UGC), New Delhi are gratefully acknowledged. The authors report no declarations of interest.