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Keywords:

  • drug–cyclodextrin complexation;
  • haloperidol;
  • skin permeability;
  • surface tension;
  • wettability

Abstract

Objectives The aim of this work was to study the effect of surface tension and contact angle on the permeation of haloperidol across human skin using cyclodextrin derivatives.

Methods Surface tension and contact angle of randomly methylated β-cyclodextrin (RM β-CD) and hydroxypropyl β-cyclodextrin (HP β-CD) solutions were measured. Haloperidol solubility and molecular modelling were carried out using the two cyclodextrin derivatives. In-vitro skin permeation was carried out using human skin models.

Key findings The highest increase in drug solubility was observed when the drug was in solution with pH 5 when compared to non-ionised solution, resulting in a 128-fold increase in the intrinsic solubility of the drug. Surface tension measurements indicate a surface-active effect for RM β-CD and HP β-CD. Contact angle measurements showed that vehicles with higher skin wettability increased the contact of the drug with the skin surface and therefore resulted in higher drug permeation across human epidermis.

Conclusions It is concluded that transdermal flux of a drug through the skin may be optimised by controlling surface tension, drug solubility and skin wettability.