Photostability and solubility improvement of beta-cyclodextrin-included tretinoin

In this work, we investigated the influence of bcyclodextrin on the photostability of tretinoin and compared the photo-chemical stability of tretinoin, either in methanol or complexed with b-cyclodextrin, when exposed both to UV and fluorescent light. The physico-chemical characterization of tretinoin-b-cyclodextrin complexes, prepared by the freeze-drying process, using different tretinoin:b-cyclodextrin molar ratios (1:1 and 1:3), was carried out in solution by phase solubility studies, 1HNMR 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 b-cyclodextrin as a function of increasing concentrations of b-cyclodextrin in aqueous solution at different pH values (i.e., 3.0, 5.5, and 7.0). Moreover, the complexation of the tretinoin with b-cyclodextrin effectively protected the photolabile drug and reduced the degradation of tretinoin induced by UV and fluorescent light, improving its photochemical stability in comparison with free drug in methanol. Indeed, dissolved tretinoin in methanol degraded very quickly and completely, while b-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 b-cyclodextrin complexation always led to a reduction of degradation, depending on the tretinoin:b-cyclodextrin molar ratio and on the drug concentration (0.2 mg/ml or 0.4 mg/m