Photodegradation of retinoic acids in liposomes by UV spectrophotometry and GC/MS

Photodegradation of retinoic acids, as tretinoin, isotretinoin and 9-cis tretinoin, in ethanol and liposomes has been studied. The light irradiation has been performed according to the conditions suggested by the ICH Guideline for photostability testing, by using a light cabinet equipped with a Xenon lamp. Samples have been irradiated in a  range between 300 and 800 nm, by means of a glass filter, according to the ID65 standard of ICH rules; the radiant power was maintained to 250 W/m2. The photodegradation process has been monitored by spectrophotometry and GC/MS. In ethanol solutions, tretinoin and isotretinoin resulted completely degraded after 8 and 4 hours of light exposure, respectively. On the contrary, 9-cis tretinoin appeared as the most stable molecule, showing a 16% residual concentration after an irradiation time of 4 hours. An isomeric transformation of the studied retinoic acids was supposed by means of UV and GC/MS spectra. Photostability of the studied retinoic acids when included in liposomes has been herein monitored. The formulations tested have shown a high degree of protection, considerably increasing drugs stability. The residual concentration detected in the inclusion complex with liposomes resulted 20 and 32% for isotretinoin and 9-cis tretinoin, respectively, while a very good value of 60% was found for tretinoin, after a light exposure of 8 hours. Since the degradation rate was found to be dependent on drug concentration, the higher stability of the tretinoin-liposome complex was supposed to be caused by the higher incorporation of this drug, probably due to its linear structure.