PHOTOSTABILITY DETERMINATION OF COMMERCIALLY AVAILABLE NIFEDIPINE ORAL DOSAGE FORMULATIONS

Nifedipine (NIF), a 1,4-dihydropyridine calcium channel antagonist, un dergoes photodegradation to dehydronifedipine (DNIF) upon exposure to ultraviolet (UV) light and to the nitroso analogue of dehydronifedipin e (NDNIF) when exposed to sunlight. NIF photodegradation products do n ot contribute to clinical activity, thus the content of NIF must remai n 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, pr oduct substitution may not be warranted. The light stability of 10 int act immediate- or controlled-release oral NIF formulations, obtained f rom several European and North American manufacturers, was studied usi ng direct continuous artificial sunlight exposure extending over a 12- week period. The content of both NIF and NDNIF for each product was me asured to determine the extent of photodecomposition using a specific and sensitive reversed-phase high pressure liquid chromatographic (HPL C) method. In addition, NIF photodegradation was measured using both p ure NIF powder and methanolic NIF solution to determine the effectiven ess of the artificial sunlight source used in this study. After 12 wee ks of artificial sunlight exposure, less than 3% of NDNIF (w/w initial NIF content) was present in each of the 10 tested dosage forms. Photo degradation 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 solut ion and pure NIF powder samples; respectively. Therefore, the tested N IF formulations all appear to be-photostable up to at least 12 weeks o f continuous artificial sunlight exposure, compared with pure NIF powd er and methanolic NIF solution. It is concluded that if therapeutic fa ilures or pharmacodynamic differences between the tested NIF formulati ons were observed, photoinstability as a major contributory factor wou ld be unlikely.