A Rapid, Automated Extraction Platform to Assess Drug Product Potency by Online Liquid Chromatography

We present a new automated active pharmaceutial ingredient (API) extraction approach with integrated analysis by online liquid chromatography (LC) to assess drug product potency. The platform consists of an extraction module for repeated dynamic pressurized solvent extractions of tablets. Extractions rely on temperature and pressurized solvents (50:50 0.1%TFA:acetonitrile, 100 bar, 3.0 mL/min) to dissolve the tablet coating (if present), disintegrate the tablet, and disperse and solubilize material. Upon exiting the extraction vessel, solvent carrying extracted material is sampled every 15 s using a dual loop LC injection valve. The valve allows direct injection of drug product extract onto a short LC column for online monitoring of the extraction process and generation of an "extract-o-gram." Autoprocessing of API peaks in the extract-o-gram facilitated direct calculation of tablet potency by integrating the area under the resulting API concentration-time curve. To assess the performance of the platform, a series of experiments was conducted with four pharmaceutical products spanning a wide API dosage range: 200 mg ibuprofen, 81 mg aspirin, and 12 mg and 1 mg tablets of Lilly development materials (Lilly A and Lilly B). Results were encouraging; using a generic set of extraction conditions, reproducible quantitative recoveries were obtained for ibuprofen (99.3% label claim, 0.5% RSD), aspirin (103.2%, 1.1% RSD), Lilly A (98.5%, 1.1% RSD), and coated and core Lilly B tablets (100.8%, 1.3% RSD and 100.9%, 2.4% RSD, respectively).