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Scientific article
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English

A water-soluble prodrug of cyclosporine A for ocular application: A stability study

Published inEuropean journal of pharmaceutical sciences, vol. 26, no. 1, p. 124-129
Publication date2005
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
Citation (ISO format)
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
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Article (Published version)
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Identifiers
ISSN of the journal0928-0987
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