کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1223454 | 967891 | 2007 | 7 صفحه PDF | دانلود رایگان |
The chemical stability of montelukast (Monte) in solution and in its solid state was studied. A simultaneous measurement of Monte and its degradation products was determined using a selective HPLC method. The HPLC system comprised a reversed phase column (C18) as the stationary phase and a mixture of ammonium acetate buffer of pH 3.5 and methanol (15:85 v/v) as the mobile phase. The UV detection was conducted at 254 nm.Monte in solution showed instability when exposed to light leading to the formation of its cis-isomer as the major photoproduct. The rate of photodegradation of Monte in solution exposed to various light sources increases in the order of; sodium < neon < tungsten < daylight < UV (254 nm). The extent of photodegradation was influenced by solvent type, where Monte was found to be most stable in 70% methanol. In solid state, Monte showed more than 20% decrease in its potency after exposure to daylight for 1 week. Also unpacked Monte chewable tablets, exposed to daylight for 2 weeks, showed a decrease of about 10% with the formation of Monte S-oxide as a major photoproduct. On the other hand, Monte film-coated tablets either unpacked or in its immediate pack showed excellent stability under the same condition. The thermal stress testing study of Monte in solutions at 65 °C showed that it is highly stable in NaOH solution, while it degrades rapidly in both acidic and H2O2 solutions. The major degradation product in the latter solvent was Monte S-oxide and it was also detected as a major degradation product in Monte tablet dosage form during the incubation at 40°C/75% RH for 6 months. Findings of this study have helped to understand the stability behavior of Monte and to establish the critical parameters, which may affect its analysis and manufacturing activities.
Journal: Journal of Pharmaceutical and Biomedical Analysis - Volume 45, Issue 3, 5 November 2007, Pages 465–471