Influence of Piroxicam: Hydroxypropyl-Beta-Cyclodextrin Complexation on the in vitro Permeation and Skin Retention of Piroxicam

Abstract

The interactions between piroxicam (Px) and hydroxypropyl-β-cyclodextrin (HPβCD) were thoroughly investigated both in solution and the solid state. The solubility studies have demonstrated the formation of a Px:HPβCD inclusion complex with 1:1 stoichiometry. The addition of propylene glycol to the medium produced less stable complexes, revealing the fact of this co-solvent probably acting as a competing agent. Equimolecular Px:HPβCD solid systems were prepared using the co-precipitation method and then fully characterized by X-ray diffractometry, infrared spectra and differential scanning calorimetry. A topical gel formulation containing Px, as inclusion complex with HPβCD, was developed in order to study the influence of Px complexation on its release rate and skin percutaneous permeation. The formation of Px:HPβCD complexes did not increase either Px release from the vehicle or its skin permeation. However, Px complexation with HPβCD allowed the incorporation of a higher quantity of Px into the gel, which resulted in a considerable increase in the Px released and permeated. Skin pretreatment with different HPβCD solutions, followed by the application of control gel, showed no enhancing capacity. The amount of Px retained in the skin, after pretreatment experiments, was found to be very similar to that obtained without skin pretreatment and was observed to be related to flux values through the skin.