Photostability and solubility improvement of β-cyclodextrin-included tretinoin

In this work, we investigated the influence of beta-cyclodextrin on the photostability of tretinoin and compared the photo-chemical stability of tretinoin, either in methanol or complexed with beta-cyclodextrin, when exposed both to UV and fluorescent light. The physico-chemical characterization of tretinoin-beta-cyclodextrin complexes, prepared by the freeze-drying process, using different tretinoin:beta-cyclodextrin molar ratios (1:1 and 1:3), was carried out in solution by phase solubility studies, H-1-NMR spectroscopy, and in solid state by infrared spectroscopy (FT-IR); these analyses confirmed the existence of an inclusion compound. Solubility study results showed that tretinoin solubility was enhanced by inclusion in beta-cyclodextrin as a function of increasing concentrations of beta-cyclodextrin in aqueous solution at different pH values (i.e., 3.0, 5.5, and 7.0). Moreover, the complexation of the tretinoin with beta-cyclodextrin effectively protected the photolabile drug and reduced the degradation of tretinoin induced by UV and fluorescent light, improving its photo-chemical stability in comparison with free drug in methanol. Indeed, dissolved tretinoin in methanol degraded very quickly and completely, while beta-cyclodextrin-included tretinoin decomposition was delayed and, after 30 days under UV exposure, the percentage of remaining drug was about 20-25% (depending on the tretinoin concentration). The photodegradation of tretinoin in methanol under fluorescent light was slower: after 5 days of irradiation it reached a photostationary state and intact tretinoin remained constant (6.6%). In conclusion, the beta-cyclodextrin complexation always led to a reduction of degradation, depending on the tretinoin:beta-cyclodextrin molar ratio and on the drug concentration (0.2 mg/ml or 0.4 mg/ml).