SUPRAMOLECULAR SYSTEMS FOR PHOTOSENSITIVE ANTIHYPERTENSIVE DRUGS

The use of light-protective wrapping has recently been replaced by the economically more viable method of using formulations incorporating suitable drugs. In this approach, photosensitive drugs are protected from light damage during preparation or administration. The design of photoprotective pharmaceutical systems presents the twofold advantage to keep unaltered the drug concentration, in order to produce a suited therapeutic efficacy, and at the same time to avoid the formation of photoproducts, that should showing toxic effects. Supramolecular "host-guest" inclusion of drugs presents another approach in solving the problem of light-sensitive drugs. Many studies have reported reduced drug degradation in cyclodextrin or liposome based supramolecular systems. The interaction of cylodextrins with labile compounds can retard drug degradation or have no effect on drug molecules reactivity. Liposomes have considerable potential in, for instance, dermatology as a result of the enhanced percutaneous penetration of photosensitive compounds like retinoic acids. Eleven 1,4-dihydropyridine antihypertensives have been included in supramolecular systems: cyclodextrin and liposomes. The development of inclusion complexes presenting both stability to light and availability for oral administration, as alternative to the solid forms is the mean goal of this study. The studied drugs easily undergo photodegradation, most frequently to nitro- and nitroso-pyridine derivatives, which have no therapeutic effect. Photodegradation tests were performed by means of a Xenon lamp irradiation (simulating the sun spectrum), in accordance with the ICH guidelines (International Conference on Harmonization). Due to the marked photosensitivity, all the studied drugs are formulated as tablets, whereas only one liquid formulation containing Nimodipine is available. For liposomal complexes the photostability was demonstrated to be function of the amount of drug entrapped. The drugs with a low molecular weight and high hydrophilicity were more easily included in liposomes. Instead, the molecular volume of the drug was the first factor in drug entrapment in cyclodextrin. The incorporation in cyclodextrin reached a mean drug recovery of more than 90% after 30 min of light exposure. In particular, cyclodextrin complexes showed a clear photostability for Amlodipine, Felodipine, Nisoldipine and Nitrendipine.