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Photostability and solubility improvement of β-cyclodextrin-included tretinoin

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Abstract

In this work, we investigated the influence of β-cyclodextrin on the photostability of tretinoin and compared the photo-chemical stability of tretinoin, either in methanol or complexed with β-cyclodextrin, when exposed both to UV and fluorescent light. The physico-chemical characterization of tretinoin-β-cyclodextrin complexes, prepared by the freeze-drying process, using different tretinoin:β-cyclodextrin molar ratios (1:1 and 1:3), was carried out in solution by phase solubility studies, 1H-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 β-cyclodextrin as a function of increasing concentrations of β-cyclodextrin in aqueous solution at different pH values (i.e., 3.0, 5.5, and 7.0). Moreover, the complexation of the tretinoin with β-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 β-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 β-cyclodextrin complexation always led to a reduction of degradation, depending on the tretinoin:β-cyclodextrin molar ratio and on the drug concentration (0.2 mg/ml or 0.4 mg/ml).

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Authors and Affiliations

  1. Dipartimento Farmaco Chimico Tecnologico, Università di Cagliari, Via Ospedale 72, 09124, Cagliari, Italy

    Carla Caddeo, Maria Manconi, Donatella Valenti & Chiara Sinico

  2. Istituto di Chimica Organica “A. Marchesini”, Università di Milano, Via Venezian 21, 20133, Milano, Italy

    Elena Pini

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  1. Carla Caddeo
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  2. Maria Manconi
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  3. Donatella Valenti
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  4. Elena Pini
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  5. Chiara Sinico
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Correspondence to Chiara Sinico.

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Caddeo, C., Manconi, M., Valenti, D. et al. Photostability and solubility improvement of β-cyclodextrin-included tretinoin. J Incl Phenom Macrocycl Chem 59, 293–300 (2007). https://doi.org/10.1007/s10847-007-9326-z

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  • DOI: https://doi.org/10.1007/s10847-007-9326-z

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