Background: HQ is used for hyper-pigmentation treatment using conventional creams and
gels. These formulations show various disadvantages like poor skin permeation, allergic reactions, and
repeated use and decreasing patient compliance.
Objectives: The present work involved formulation, statistical optimization, and characterization of
Nanostructured Lipid Carriers (NLCs) for efficient topical delivery of hydroquinone (HQ) for hyperpigmentation
Methods: The NLCs were optimized exploring Box–Behnken Design (BBD) using three independent
variables and two dependent variables. Formulation having the minimum size and maximum drug entrapment
was considered as optimized formulation. The optimized formulation was evaluated for drug
release followed by its freeze-drying. The freeze-dried formulation was subjected to Differential Scanning
Calorimetry (DSC) analysis, X-Ray Diffraction (XRD) analysis, and Fourier Transform-Infrared
spectroscopy (FT-IR) analysis. Furthermore, NLCs based gel was prepared by using Carbopol 934 as a
gelling agent. NLCs based gel was evaluated for skin permeation, skin retention, and skin distribution
(through confocal microscopic analysis) using pig ear skin.
Results: Optimized NLCs showed smaller particle size [(271.9 ± 9) nm], high drug entrapment [(66.4 ±
1.2) %], tolerable polydispersity index (PDI) (0.221 ± 0.012), and zeta potential [(-25.9 ± 1.2) mV]. The
FT-IR analysis revealed excellent compatibility between HQ and other excipients. The Carbopol 934
gel containing NLCs showed high transdermal flux [(163 ± 16.2) μg/cm2/h], permeability coefficient
(0.0326 ± 0.0016), and skin permeation enhancement ratio (3.7 ± 0.4) compared to marketed cream of
HQ. The results of confocal microscopic (CLSM) analysis revealed the accumulation of optimized
NLCs in the lower epidermal layers of skin.
Conclusion: NLCs based gel was considered effective in the topical delivery of HQ to treat hyperpigmentation
due to high skin permeation, skin retention, and prolonged release of HQ.