SOLID STATE COMPATIBILITY STUDIES BETWEEN MONTELUKAST SODIUM AND LEVOCETIRIZINE

摘要

Objective: The aim of this research is to evaluate montelukast (MNT)-levocetirizine (LVZ) incompatibility when they gather in one solid dosage form. Methods: Both drugs and their binary mixture (2:1) (MNT-LVZ) were subjected to the following condition: 25°C/60% RH and 40°C/75% RH for 14 weeks. Samples were withdrawn and analyzed using stability-indicating high-performance liquid chromatography (HPLC) method at time intervals (0, 1, 4, 14 weeks). Further investigations were carried out using differential scanning calorimeter (DSC), Fourier transform infrared (FTIR), and X-ray powder diffraction (XRPD) Result: On the basis of HPLC results, the degradation percentage of both drugs in binary mixtures was <10% indicating no chemical interaction; this was confirmed by all FTIR results except new band 668 cm?1 appeared in the spectrum of the mixture after storing 14 weeks at 40°C/75% RH, revealing possible hydrogen bond formed in the mixture. DSC and XRPD revealed possible physical interaction including phase transformation (release the acid form of montelukast and basic form of levocetirizine and sodium chloride in the medium); this may affect dissolution rate and bioavailability. Conclusion: The results obtained from this research gave an evidence to formulate MNT and LVZ in stable fixed-dose combination for the effective treatment of allergic diseases