Influence of piroxicam: hydroxypropyl-beta-cyclodextrin complexation on the in vitro permeation and skin retention of piroxicam.
The interactions between piroxicam (Px) and hydroxypropyl-beta-cyclodextrin (HPbetaCD) were thoroughly investigated both in solution and the solid state. The solubility studies have demonstrated the formation of a Px:HPbetaCD 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:HPbetaCD 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 HPbetaCD, was developed in order to study the influence of Px complexation on its release rate and skin percutaneous permeation. The formation of Px:HPbetaCD complexes did not increase either Px release from the vehicle or its skin permeation. However, Px complexation with HPbetaCD 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 HPbetaCD 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.
Doliwa
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A
Centro Galénico, Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Navarra, Pamplona, España.
Santoyo
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S
Ygartua
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P
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000465:Algorithms; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003505:Cyclodextrins; D005079:Excipients; D066298:In Vitro Techniques; D008297:Male; D010894:Piroxicam / Q000493:pharmacokinetics*; D051381:Rats; D012869:Skin Absorption; D012995:Solubility; D013055:Spectrophotometry, Infrared; D047392:beta-Cyclodextrins
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003505:Cyclodextrins; D005079:Excipients; D047392:beta-Cyclodextrins; D010894:Piroxicam; D000073738:2-Hydroxypropyl-beta-cyclodextrin