Abstract
Purpose
This study aimed to elucidate the compatibility between levocetirizine dihydrochloride (LCZ) and montelukast sodium (MTL) and to improve their stability through the complexation of LCZ with ion-exchange resins (IERs).
Methods
Compatibility studies between LCZ and MTL were conducted under stress conditions. LCZ-IER complexes (LICs) were prepared via a batch method to prevent interactions with MTL and reduce the acidity and bitterness of LCZ. The physicochemical properties, pH, in vitro taste, and release profiles of the resultant LICs were investigated. The effect of LICs on the stability of the LCZ and MTL was evaluated based on the content of related substances.
Results
Discoloration was observed in the physical mixture of LCZ and MTL, and the contents of LCZ- and MTL-related substances increased. The increase in the content of MTL-related substances was particularly noticeable. LICs with different LCZ-to-IER ratios were prepared, and regardless of the ratio, LCZ was loaded into the IER via intermolecular interactions. Due to the change from LCZ to LICs, the unpleasant taste and acidity of LCZ was effectively reduced without retarding the release of LCZ. In addition, the content of LCZ- and MTL-related substances was significantly reduced, which attributed to the change in the salt form of the LCZ and the absence of LCZ to the surface of LICs.
Conclusion
The incompatibility between LCZ and MTL was elucidated quantitatively and resolved by the complexation of LCZ and IER. This finding may provide a promising approach for formulation design composed of incompatible drugs such as LCZ and MTL.
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Acknowledgements
This work was supported by Korea Initiative for fostering University of Research and Innovation Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (No. 2020M3H1A1077095).
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Park, HR., Seok, S.H. & Park, ES. Complexation of levocetirizine with ion-exchange resins and its effect on the stability of powder mixtures containing levocetirizine and montelukast. J. Pharm. Investig. 53, 377–388 (2023). https://doi.org/10.1007/s40005-022-00604-9
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DOI: https://doi.org/10.1007/s40005-022-00604-9