Formulation and assessment of hydroxyzine HCL solid lipid nanoparticles by dual emulsification technique for transdermal delivery

Biomed Pharmacother. 2021 Nov:143:112130. doi: 10.1016/j.biopha.2021.112130. Epub 2021 Sep 21.

Abstract

Hydroxyzine HCL (HHCL) is an antihistamine, used for the treatment of allergic skin conditions. The purpose of this study was to achieve a dual phase drug delivery rate across the intact skin, to enhance HHCL permeation through the stratum corneum, to assess the peripheral H1-antihistaminic activity and the extent to which HHCL was systemically absorbed from transdermal gel loaded with solid lipid nanoparticles (SLNs), as well as to avoid its extreme bitterness. According to 23 factorial design, eight formulations of HHCL-SLNs were prepared by the double emulsification method. Lipid type (XA), surfactant concentration (XB) and co-surfactant concentration (XC) were the independent variables. All formulations were characterized for their surface morphology, particle size, entrapment efficiency and in-vitro drug release study. The optimized formula that provides greater desirability was then incorporated into the transdermal gel. In addition, the efficacy of the developed gel was tested in-vivo using 2,4-Dinitrochlorobenzene induced atopic dermatitis as lesion model in mice. F4 showed an average diameter 111 nm ± 0.03, zeta potential - 30 MV ± 2.4 and EE 75.2% ± 4.4. TEM images showed spherical, smooth morphology with uniform particles distribution. In-vivo study demonstrated potent antipruritic efficacy of transdermal gel in atopic dermatitis such as induced lesions compared to HHCL gel. Hence, HHCL solid lipid nanoparticles transdermal gel may be considered as potential for delivery of HHCL and alternatively to traditional oral use.

Keywords: Atopic dermatitis; Hydroxyzine HCL (HHCL); Solid lipid nanoparticles (SLNs); Transdermal gel; W/O/W type double emulsification method.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Antipruritics / administration & dosage*
  • Antipruritics / chemistry
  • Antipruritics / metabolism
  • Dermatitis, Atopic / immunology
  • Dermatitis, Atopic / metabolism
  • Dermatitis, Atopic / prevention & control*
  • Disease Models, Animal
  • Drug Carriers*
  • Drug Compounding
  • Drug Liberation
  • Gels
  • Histamine H1 Antagonists / administration & dosage*
  • Histamine H1 Antagonists / chemistry
  • Histamine H1 Antagonists / metabolism
  • Hydroxyzine / administration & dosage*
  • Hydroxyzine / chemistry
  • Hydroxyzine / metabolism
  • Lipids / chemistry*
  • Male
  • Mice
  • Nanoparticles*
  • Nanotechnology
  • Rats
  • Skin / metabolism*
  • Skin Absorption*
  • Surface Properties

Substances

  • Antipruritics
  • Drug Carriers
  • Gels
  • Histamine H1 Antagonists
  • Lipids
  • Hydroxyzine