Bromocriptine Nanoemulsion-Loaded Transdermal Gel: Optimization Using Factorial Design, In Vitro and In Vivo Evaluation

Abstract

Bromocriptine mesylate (BCM), a dopaminergic agonist administered orally, exhibits retarded bioavailability owing to poor absorption and extreme first-pass metabolism. The objective of the current study was to develop, characterize, and statistically optimize BCM nanoemulsion (BCM-NE) loaded into a gel (BCM-NE gel) to evaluate its potential for improved permeation of BCM through the transdermal route, thereby improving its pharmacokinetic profile. BCM-NE was prepared by o/w spontaneous emulsification method and the effects of different formulation variables on the critical attributes of NE like globule size were investigated by implementing factorial design. The optimized formulation exhibited a mean globule size of 160 ± 6.5 nm, zeta potential of − 20.4 ± 1.23 mV, and drug content of 99.45 ± 1.9%. Ex vivo permeation studies across rat skin exhibited a significant enhancement in permeation, i.e., enhancement ratio (ER) of ~ 7.4 and 5.86 for BCM-NE and BCM-NE gel, respectively, when compared with aqueous BCM suspension gel. In vivo pharmacokinetic studies performed in rats demonstrated a higher and prolonged drug release of BCM from BCM-NE gel when compared to oral aqueous BCM suspension. The AUC0–t for BCM-NE gel and BCM suspension was found to be 562.54 ± 77.55 and 204.96 ± 51.93 ng/ml h, respectively. The relative bioavailability (%F) of BCM was shown to be enhanced 274% by BCM-NE gel. Histopathological studies demonstrated the safety and biocompatibility of the developed system. All the above results proved that the BCM-NE gel could be a superior and patient-compliant alternative to oral delivery in the management of PD.