The difficulties for a photolabile drug in topical formulations: the case of diclofenac.
Topical commercial formulations containing diclofenac (DC) were submitted to photostability tests, according to the international rules, showing a clear degradation of the drug. The degradation process was monitored by applying the multivariate curve resolution technique to the UV spectral data from samples exposed to stressing irradiation. This method was able to estimate the number of components evolved as well as to draw their spectra and concentration profiles. Three photoproducts (PhPs) were resolved by the analysis of photodegradation kinetics, according to two consecutive reactions with a mechanism postulated as DC>PhP₁>PhP₂ and PhP₃. Photodegradation rate of DC in gel was found to be very fast, with a residual content of 90% only after 3.90 min under a radiant exposure of 450 Wm(-2). Because of a very slow skin uptake of DC, a prolonged time of exposure to light could lead to a significant decrease of drug available or the uptake of undesired photoproducts. New gel formulations were designed to increase the photostability of DC by incorporating chemical light-absorbers or entrapping the drug into cyclodextrin. Drug photostability resulted increased significantly in comparison with that of the commercial formulations. The gel containing the light-absorbers such as octisilate, octyl methoxycinnamate and a combination thereof showed a residual DC of 90% up to 12.22 min, 13.75 min and 15.71 min, respectively, under the same irradiation power. The best results were obtained by incorporating the drug in β-cyclodextrin with a degradation of 10% after 25.01 min of light exposure.
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, CS, Italy. Electronic address: giuseppina.ioele@unical.it.
Giuseppina
G
Ioele
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, CS, Italy.
Michele
M
De Luca
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, CS, Italy.
Lorena
L
Tavano
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, CS, Italy.
Gaetano
G
Ragno
D065638:Absorption, Radiation; D000279:Administration, Cutaneous; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry / Q000528:radiation effects*; D002626:Chemistry, Pharmaceutical; D002934:Cinnamates / Q000737:chemistry; D004008:Diclofenac / Q000008:administration & dosage / Q000737:chemistry / Q000528:radiation effects*; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D005782:Gels; D007700:Kinetics; D016018:Least-Squares Analysis; D008956:Models, Chemical; D015999:Multivariate Analysis; D010782:Photolysis; D012459:Salicylates / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods; D047392:beta-Cyclodextrins / Q000737:chemistry
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002934:Cinnamates; D005079:Excipients; D005782:Gels; D012459:Salicylates; D047392:beta-Cyclodextrins; D004008:Diclofenac; C103422:2-ethylhexyl salicylate; C118580:octylmethoxycinnamate
Cyclodextrin; Diclofenac; Gel formulation; Light-absorbers agents; Photodegradation; Photostabilization