Interaction of tenoxicam with cyclodextrins and its influence on the in vitro percutaneous penetration of the drug.
Solid complexes of tenoxicam (TEN) with cyclodextrins (CDs), in a 1:1 molar ratio, were obtained by the coprecipitation method and characterized by x-ray diffractometry, infrared spectroscopy, and differential scanning calorimetry. The binding capacity of the CDs with TEN was also demonstrated in aqueous solution and in water-propylene glycol mixtures. The purpose of this study was to determine the effect of CDs on the in vitro percutaneous penetration of TEN from carbopol gels, taking into account the role of the CD cavity size and the nature of the substituents. The effect of pretreatment was studied too. In vitro permeation experiments were carried out on Franz diffusion cells using cellulose nitrate membranes and abdominal rat skin. In these results, the release rates of the drug scarcely decreased when the CDs were added, probably because of a lower concentration of the free drug and an increased gel viscosity. However, it was also found that CDs, particularly gamma-CD and M-beta-CD, can improve slightly TEN absorption through the skin. Pretreatment studies with CDs, however, provided no effects on TEN permeation, but lag time was markedly reduced, suggesting a faster partitioning of TEN into the skin. Therefore, the use of pretreatment with CDs would be interesting when a quick action of the drug is desired.
Larrucea
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E
Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Navarra, 31080 Pamplona, Spain. larrucea@unav.es
Arellano
A
A
Santoyo
S
S
Ygartua
P
P
D000180:Acrylic Resins; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D002152:Calorimetry, Differential Scanning; D003505:Cyclodextrins / Q000494:pharmacology*; D004337:Drug Carriers; D004347:Drug Interactions; D008297:Male; D010894:Piroxicam / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D011145:Polyvinyls / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012869:Skin Absorption / Q000187:drug effects*; D014961:X-Ray Diffraction
D000180:Acrylic Resins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003505:Cyclodextrins; D004337:Drug Carriers; D011145:Polyvinyls; D011480:Protease Inhibitors; C006912:carboxypolymethylene; D010894:Piroxicam; C032801:tenoxicam