title: Effect of light and heat on the stability of montelukast in solution and in its solid state.
abstract: 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 degrees 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 degrees 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.
authors: The Jordanian Pharmaceutical Manufacturing Company, Naor, Jordan. momari@jpm.com.jo
authors: Mahmoud M
authors: MM
authors: Al Omari
authors: Rufaida M
authors: RM
authors: Zoubi
authors: Enas I
authors: EI
authors: Hasan
authors: Tariq Z
authors: TZ
authors: Khader
authors: Adnan A
authors: AA
authors: Badwan
mesh_terms: D000085:Acetates / Q000737:chemistry*; D018927:Anti-Asthmatic Agents / Q000737:chemistry*; D002021:Buffers; D002851:Chromatography, High Pressure Liquid; D003521:Cyclopropanes; D004355:Drug Stability; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D008027:Light; D015394:Molecular Structure; D011804:Quinolines / Q000737:chemistry*; D012996:Solutions; D012997:Solvents / Q000737:chemistry; D013440:Sulfides; D013607:Tablets
chemical_list: D000085:Acetates; D018927:Anti-Asthmatic Agents; D002021:Buffers; D003521:Cyclopropanes; D011804:Quinolines; D012996:Solutions; D012997:Solvents; D013440:Sulfides; D013607:Tablets; C093875:montelukast