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A water-soluble prodrug of cyclosporine A for ocular application: A stability study
|Published in||European Journal of Pharmaceutical Sciences. 2005, vol. 26, no. 1, p. 124-129|
|Abstract||UNIL088 is a water-soluble prodrug of cyclosporine A (CsA) developed for topical eye delivery. Such a prodrug has to fulfil two paradoxical requirements as it must be rapidly hydrolysed under physiological conditions but also retain a long shelf-life in aqueous media. This study has been conducted to explore the stability of UNIL088 formulated as an eyedrop solution. The stability study of the prodrug was performed over a pH range of 5–7 at 20 °C and at various ionic strengths. The molecule was more stable at pH 5 than at pH 7 with conversion rate constant of 3.2 × 10−3 and 26.0 × 10−3 days−1, respectively. The effect of temperature was studied at four different temperatures and activation energy was determined. Conversion of UNIL088 followed a pseudo-first-order kinetic with an activation energy of 79.4 kJ mol−1. Due to its low solubility, CsA generated precipitated in the solution. The average size of CsA precipitates, determined by photon spectroscopy, was 0.22 and 1.08 μm at 7 and 14 days, respectively. The hydrolysis mechanism was partially elucidated by identification of the intermediate pSer-Sar-CsA.|
|Keywords||Cyclosporine A — Prodrug — Stability — Solubility — Conversion mechanism — Shelf-life — Precipitation — Administration — Topical — Chromatography — High Pressure Liquid — Drug Stability — Hydrogen-Ion Concentration — Hydrolysis — Immunosuppressive Agents — Mass Spectrometry — Ophthalmic Solutions — Particle Size — Photons — Spectrum Analysis — Temperature|
|Research group||Groupe Gülaçar|
|LALLEMAND, Frédéric et al. A water-soluble prodrug of cyclosporine A for ocular application: A stability study. In: European Journal of Pharmaceutical Sciences, 2005, vol. 26, n° 1, p. 124-129. doi: 10.1016/j.ejps.2005.05.003 https://archive-ouverte.unige.ch/unige:3262|