Mefloquine (MQ) is an antimalarial medication prescribed to treat or malaria prevention.. When taken by children, vomiting usually occurs, and new doses of medication frequently need to be taken. So, developing pediatric medicines using taste-masked antimalarial drug complexes is mandatory for the success of mefloquine administration. The hypothesis that binding mefloquine to an ion-exchange resin (R) could circumvent the drug’s bitter taste problem was proposed, and solid-state ¹³C cross-polarization magic angle spinning (CPMAS) NMR was able to follow MQ–R mixtures through chemical shift and relaxation measurements. The nature of MQ–R complex formation could then be determined. Impedimetric electronic tongue equipment also verified the resinate taste-masking efficiency in vitro. Variations in chemical shifts and structure dynamics measured by proton relaxation properties (e.g., T1ρ^H) were used as probes to follow the extension of mixing and specific interactions that would be present in MQ–R. A significant decrease in T1ρ^H values was observed for MQ carbons in MQ–R complexes, compared to the ones in MQ (from 100–200 ms in MQ to 20–50 ms in an MQ–R complex). The results evidenced that the cationic resin interacts strongly with mefloquine molecules in the formulation of a 1:1 ratio complex. Thus, ¹³C CPMAS NMR allowed the confirmation of the presence of a binding between mefloquine and polacrilin in the MQ–R formulation studied.

Background: The pharmaceutical industry is constantly looking for a better way to ensure and improve its products' safety, quality, and effectiveness. Since there are many attributes of the drug substance and excipients that could potentially affect the Critical Quality Attributes (CQAs) of the intermediates and the final product, the evaluation of the raw material's physicochemical characteristics is crucial as they directly affect the quality, safety, efficacy, and lot-to-lot consistency. Scientists rely on methods, like HPLC, HPTLC, LC-MS, GC-MS, and NMR, to analyze these substances. The advantage of NMR is that it is considered a primary analytical method compared to other analytical techniques. Objective: This work aimed to present a simple, rapid, specific, and accurate method by proton Nuclear Magnetic Resonance spectroscopy (1H-NMR) developed to determine the activity of the antiretroviral Efavirenz’s (EFZ) Active Pharmaceutical Ingredient (API). The method was based on quantitative NMR spectroscopy (qNMR). Methods: A Bruker Avance spectrometer (11.7 Tesla, 500 MHz for 1H) with a 5mm probe was used. The 1H-NMR signal at 7.54 ppm corresponding to the analyte of interest was employed to quantify the drug. The method was validated for specificity, selectivity, intermediate precision, linearity, range of work, accuracy, and robustness. Results: The method developed was specific and linear (r2 = 0.9998) with a value between 4.30 mg/mL and 12.40 mg/mL. The relative standard deviation for accuracy and precision was 0.4% or less. The method's robustness was demonstrated by changing four different parameters, and the difference among each was 1.2% or less. The results of this work have been found to be in agreement with those obtained from High-performance Liquid Chromatography (HPLC) analysis. Conclusion: The proposed method has been found to be a valuable and practical tool for quality control. Its applicability to determining many APIs and saving solvent use and time is highlighted.

Malaria remains a major global health burden, especially in children under the age of five. Pediatric treatment often requires tablet fragmentation for its dose adjustment according to body weight, which intensifies bitterness and may reduce treatment adherence. Complexation of bitter-tasting drugs with ion-exchange resins for taste masking is a promising strategy to improve palatability. Here, we evaluated whether a chloroquine–resin complex (CLQ-R) preserves the pharmacokinetic profile and antimalarial efficacy of chloroquine diphosphate (CLQ) while masking its bitter taste. CLQ-R was prepared at a 1:1 (w/w) drug-to-resin ratio using polacrilin potassium (Amberlite IRP88). The in vitro antimalarial activity of CLQ-R was assessed using Plasmodium falciparum 3D7 strain, and the parasite proliferation was determined by SYBR Green DNA-staining. CLQ plasma concentrations and mice biochemical parameters were evaluated following oral administration of CLQ or CLQ-R. The in vivo antimalarial activity was evaluated in P. berghei ANKA–infected C57BL/6 mice using the four-day suppressive and recrudescence tests, with parasitemia assessed by flow cytometry. Taste perception was determined by 48-hour two-bottle preference test. CLQ-R displayed similar plasma concentration and biochemical profiles to CLQ. CLQ-R was able to maintain a strong in vitro antimalarial activity with IC50 of 30 nM with minimal hemolytic activity and reduced in vivo parasitemia by >95%. Notably, mice exhibited a 15.5% higher preference for CLQ-R, indicating improved palatability. These findings demonstrate that CLQ-R preserves CLQ pharmacological activity while masking its bitter taste, supporting its potential as a pediatric-friendly antimalarial formulation.