Brompheniramine maleate (BPM) is an alkylamine class antihistamine primarily used as an adult and pediatric over-the-counter medication for the treatment of common cold and allergic rhinitis. Complexation of BPM with tannic acid (TA), a more palatable formulation, was attempted for sustained release effect to improve patient compliance. BPM-TA complexes and BPM formulations were prepared in-house by solvent evaporation method, and evaluated for several factors that may affect safety and efficacy of the product. Drug assay and content uniformity tests were conducted and found to be within ±5% of added brompheniramine. The prepared tannate complexes were also tested for drug release in PBS buffer pH 6.8 and 0.1N HCl and % dissolved in 24hr were found to be 61.5 ±9.8%, and 101.6 ±0.64%, respectively. The assayed complex mixtures of brompheniramine were weighed (6mg) and filled in size 3L capsules for in vivo evaluation. A bioavailability study of BPM-TA complexes in porcine pigs was conducted and compared to the bioavailability of BPM. Plasma samples were collected over 48 hours and analyzed by a validated LCMS method with linearity range 0.2-20 ng/mL and mean intra-day accuracy 98.0-105.3%, mean inter-day accuracy 102-104%, mean intra-day precision 0.93-5.73%, and mean inter-day precisions 1.96-4.84%, across the quality control (QC) standards, 0.2, 0.4, 4, and 20ng/mL over the analytical range. The mean recoveries were 91-98.3% for brompheniramine at four QC levels and no significant matrix effect (&lt; 2.13%) was observed in this assay. The pharmacokinetic parameters were calculated by Phoenix WinNonLin 6.4 using non-compartmental analysis. The absorption of brompheniramine maleate was slightly fast with a mean Tmax of 1.5 hr compared to mean Tmax of 2.43 hr for brompheniramine tannate, and brompheniramine maleate has higher Cmax (6.75 ng/mL) and AUC0-t (16.34 ng.hr/mL) compared to brompheniramine tannate (3.27 ng/mL) and (12.23 ng.hr/mL), respectively. The bioavailability of BPM-TA complexes showed slight sustained release compared to BPM. In conclusion, this pre-clinical approach is promising for screening taste-masked pediatric formulations.

Bioavailability evaluation of two taste-masked pediatric products of brompheniramine in porcine models

254th National Meeting (2017)

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