Effect of light and heat on the stability of montelukast in solution and in its solid state

• Published in: Journal of pharmaceutical and biomedical analysis 2007-11, Vol.45 (3), p.465-471
• Main Authors: Al Omari, Mahmoud M., Zoubi, Rufaida M., Hasan, Enas I., Khader, Tariq Z., Badwan, Adnan A.
• Format: Article
• Language: English
• Subjects: Acetates - chemistry; Analysis; Analytical, structural and metabolic biochemistry; Anti-Asthmatic Agents - chemistry; Biological and medical sciences; Buffers; Chemical stability; Chromatography, High Pressure Liquid; Drug Stability; Fundamental and applied biological sciences. Psychology; General pharmacology; Hot Temperature; HPLC; Hydrogen-Ion Concentration; Light; Medical sciences; Molecular Structure; Montelukast; Oxidation; Pharmacology. Drug treatments; Photodegradation; Quinolines - chemistry; Solutions; Solvents - chemistry; Tablets
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2007.07.014

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 H 2O 2 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.