Accelerated photostability study of tretinoin and isotretinoin in liposome formulations

Abstract

The photodegradation of retinoic acids, tretinoin and isotretinoin, in ethanol and liposomes was studied. The light irradiation was performed according to the conditions suggested by the ICH Guideline for photostability testing by using a Xenon lamp within a wavelength range of 300–800 nm. The photodegradation process was monitored by UV spectrophotometry. In ethanol solution, tretinoin and isotretinoin undergo complete isomerization just within a few seconds of light exposure to give 13- cis and 9- cis isomers, respectively. The 13- cis isomer from tretinoin undergoes in turn a slow isomerization to the same 9- cis isomer. Both retinoic acids incorporated in liposome complexes showed an increased stability in comparison to the ethanol solutions. In particular for tretinoin, a residual concentration of 60% was still present after a light irradiance of 3470 kJ/m 2, by means of a 250 W/m 2 light power for 240 min, versus a residual value of just 8% measured at the same time in ethanol solution. Moreover, the isomerization rate in liposomes resulted reduced for isotretinoin and practically irrelevant for tretinoin. The degradation rate was found to be dependent on the drug concentration. The better stability of the tretinoin in liposome complex was supposed to be related to its higher incorporation value due to the linear structure of the molecule.