Desing of drug photoprotective systems based on supramolecular matrices

Photostability of drugs is an emerging topic in the pharmaceutical research of the last years and new compounds are frequently added to the list of photolabile drugs. The design of photo-protective systems is essential in the process of drug registration. Recent studies on the drug photostabilization are focalized on the formulation of drugs in supramolecular systems, known as host-guest systems and characterized by the ability to entrap the drug involving only noncovalent bonding interactions. The most known supramolecular aggregates studied as photo-protective carriers are Liposomes and Cyclodextrins. An in-depth study about the photoprotective ability of supramolecular systems for eleven 1,4-dihydropyridine antihypertensives has been performed. These drugs easily undergo photodegradation, most frequently to nitro- and nitroso-pyridine derivatives, which have no therapeutic effect. Due to the marked photosensitivity, all the studied drugs are at the moment formulated as tablets, whereas only one liquid formulation containing Nimodipine is available. The mean goal of this study was the development of cyclodextrin and liposome complexes presenting both stability to light and availability for oral administration, as alternative to the solid forms. The photodegradation process was performed by means of a Xenon lamp irradiation, in accordance with the ICH guidelines for photostability testing, and monitored by spectrophotometry. The exposure to light of the drugs in solution indicated a high light-sensitivity for all of them. In particular, Lacidipine, Manidipine, Nifedipine and Nimodipine reached a 50% degradation level in less than five minutes. In contrast, the solid form of all the drugs demonstrated an effective stability to light. The inclusion in liposomes showed a photostabilization similar to that recorded for the commercial solid formulations for Felodipine, Amlodipine, Nitrendipine, Nimodipine and Nicardipine. In contrast, the inclusion of the other drugs did not give analogous satisfactory results. Photostability was demonstrated to be function of the amount of drug entrapped. Liposome inclusion resulted favoured for drugs with a low molecular weight and high hydrophilicity. The incorporation in cyclodextrin reached a mean drug recovery of more then 90% after 30 min of light exposure. In particular, cyclodextrin complexes showed a clear photostability for Amlodipine, Felodipine, Nisoldipine and Nitrendipine. The major factor in drug entrapment in cyclodextrin was the molecular volume of the drug.