Topical delivery of local anesthetics has been an area of interest for researchers considering the barrier properties of skin and unfavorable physicochemical properties of drugs. In the present study, efforts have been made to modify the in vivo efficacy of eutectic mixture of lidocaine and prilocaine by exploiting the phospholipid modified microemulsion based delivery systems. The strategic QbD (D-optimal mixture design) enabled systematic optimization approach, after having obtained the isotropic area of interest by ternary phase diagram, has resulted into the system with most desirable attributes. Latter include nano-scale, globular structures with an average size of 40.6 nm, as characterized by TEM and DLS. The optimized microemulsion systems in gel dosage forms revealed the better permeability over commercial cream (CC) through abdominal rat skin. Enhancement in the flux from MOPT-NMP gel was 3.22-folds for prilocaine and 4.94-folds for lidocaine, in comparison to that of CC. This enhanced skin permeability is very well reflected in the in vivo studies, wherein intensity and duration of action was augmented significantly. The skin compliance of the optimized formulation was revealed in histopathological studies. The overall benefit relating to efficacy and safety-compliance could be correlated to the uniqueness of the carriers, composed of phospholipids and other components. Hence, the developed phospholipid-microemulsion based gel formulation has been proposed as more useful alternative for the topical delivery of lidocaine and prilocaine.

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 3(3) 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.

Background: Psoriasis, a recurrent, chronic inflammatory disorder of skin, is a common problem in middle age and elderly people. Thymoquinone (TQ), a lipid soluble benzoquinone is the major active ingredient of volatile oil of Nigella sativa (NS), possesses good anti-psoriatic activity. However, its hydrophobicity, poor aqueous solubility, and photosensitive nature obstructs its development. Therefore, in the present research work, ethosomal vesicles (EVs) loaded with TQ were assessed for its anti-psoriatic potential employing mouse-tail model. Methods: TQ-loaded EVs were prepared by cold method, and characterized for various essential attributes, viz. particle size, morphology, percent drug entrapment, flexibility, rheological and textural analysis, and skin absorption. The optimized formulation was finally evaluated for anti-psoriatic activity on Swiss albino mice employing mouse-tail model for psoriasis. Results: The spherical shaped vesicles were in the nanosize range, and had high flexibility. The EVs incorporated hydrogel was rheologically acceptable and resulted in substantial TQ retention in the skin layers. The % anti-psoriatic drug activity was observed to be substantially better in the case of TQ-loaded ethosomal gel vis-à-vis plain TQ, NS extract, and marketed formulation. Conclusions: The promising outcomes of the current studies ratify the superiority of TQ-loaded phospholipid-based vesicular systems for the management of psoriasis over other studied test formulations. This study, thus open promising avenues for topical application of TQ in the form of EV hydrogel.