Solid-State NMR Characterization of Mefloquine Resinate Complexes Designed for Taste-Masking Pediatric Formulations

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Analytical Chemistry

Background:

• Mefloquine (MQ) is an essential antimalarial drug.
• Pediatric administration of MQ is challenging due to its bitter taste, leading to poor adherence.
• Taste-masking strategies are necessary for effective pediatric mefloquine formulations.

Purpose of the Study:

• To develop a taste-masked mefloquine formulation using an ion-exchange resin.
• To investigate the complex formation between mefloquine and the ion-exchange resin.
• To evaluate the in vitro taste-masking efficiency of the mefloquine-resin complex.

Main Methods:

• Solid-state 13C cross-polarization magic angle spinning (CPMAS) NMR spectroscopy was used to characterize the mefloquine-resin (MQ-R) mixtures.
• Chemical shift and relaxation measurements (T1ρH) were employed to monitor complex formation and interactions.
• Impedimetric electronic tongue equipment was utilized to assess the in vitro taste-masking efficacy.

Main Results:

• CPMAS NMR demonstrated changes in chemical shifts and dynamics, indicating MQ-R complex formation.
• Proton relaxation measurements (T1ρH) showed a significant decrease in MQ carbons within MQ-R complexes (100-200 ms to 20-50 ms).
• Electronic tongue confirmed the taste-masking efficiency of the resinate in vitro.
• A 1:1 complex formation between mefloquine and the cationic resin was evidenced.

Conclusions:

• Binding mefloquine to an ion-exchange resin is an effective strategy for taste-masking.
• Solid-state NMR is a valuable tool for characterizing drug-resin interactions and complex formation.
• The developed MQ-R formulation shows promise for improved pediatric antimalarial treatment.