PHOTOSTABILITY DETERMINATION OF COMMERCIALLY AVAILABLE NIFEDIPINE ORAL DOSAGE FORMULATIONS

Nifedipine (NIF), a 1,4-dihydropyridine calcium channel antagonist, undergoes photodegradation to dehydronifedipine (DNIF) upon exposure to ultraviolet (UV) light and to the nitroso analogue of dehydronifedipine (NDNIF) when exposed to sunlight. NIF photodegradation products do not contribute to clinical activity, thus the content of NIF must remain uniform between equipotent formulations. Large differences in light stability between bioequivalent NIF products could potentially result in the therapeutic failure of unstable preparations. Consequently, if large photostability differences do exist between NIF preparations, product substitution may not be warranted. The light stability of 10 intact immediate- or controlled-release oral NIF formulations, obtained from several European and North American manufacturers, was studied using direct continuous artificial sunlight exposure extending over a 12-week period. The content of both NIF and NDNIF for each product was measured to determine the extent of photodecomposition using a specific and sensitive reversed-phase high pressure liquid chromatographic (HPLC) method. In addition, NIF photodegradation was measured using both pure NIF powder and methanolic NIF solution to determine the effectiveness of the artificial sunlight source used in this study. After 12 weeks of artificial sunlight exposure, less than 3% of NDNIF (w/w initial NIF content) was present in each of the 10 tested dosage forms. Photodegradation was greater than 10% (w/w initial NIF content) in similar to 5-10 min (mean t(1/2) = 31 min), and in similar to 24 h (mean t(1/2) = 7.7 days) of artificial sunlight exposure for methanolic NIF solution and pure NIF powder samples; respectively. Therefore, the tested NIF formulations all appear to be-photostable up to at least 12 weeks of continuous artificial sunlight exposure, compared with pure NIF powder and methanolic NIF solution. It is concluded that if therapeutic failures or pharmacodynamic differences between the tested NIF formulations were observed, photoinstability as a major contributory factor would be unlikely.