Effect of consumer reconstitution practices on acetaminophen concentration in sachet formulations: Pilot study

Abstract

Background: Single-dose powder sachets are used to overcome solubility limitations of several actives such as acetaminophen. After reconstitution,residual deposits and sedimentation may reduce the delivered dose.
Objectives: Develop and validate a rapid assay for acetaminophen quantification in sachet preparations and evaluate consumer reconstitution practices to generate provisional, product-specific recommendations.
Methods: Prospective pilot study on four commercial sachet products. Twenty-eight volunteers (7 per product) simulated preparation and administration. Studied preparation variables were: reconstitution volume (mL) and stirring time (s). An aliquot of each preparation was analyzed by the validated chromatography (HPLC) method. Correlation coefficients between measured concentrations and preparation variables were calculated. Product-specific predictive models were generated for variables showing significant association. Optimal reconstitution conditions were estimated from these models.
Results: Inter-individual variability was large: SD(volume) = 27.76 mL; SD(stirring time) = 8.98 s. Recovered concentrations ranged from 59.4% to 99.7% of the predicted value; only 4/28 preparations reached ≥97.5% of expected concentration. Product-specific optimal conditions calculated were — Product 1: stir 37 s, volume 90 mL; Product 2: volume 178 mL, stir 7 s; Product 3: stir 11 s, volume 64 mL.
Conclusion: In this exploratory pilot, consumer reconstitution of acetaminophen sachets produced substantial variability and frequent under-delivery. The validated HPLC assay enabled derivation of provisional, product-specific reconstitution parameters.