Quantitative determination of acrylate-based copolymer retarding layers ondrug granules using pyrolysis gas chromatography

A pyrolysis-GC (PY-GC) method for the quantitative determination of poly(et hylacrylate-methylmethacrylate) (PEAMMA) layers on granules for pharmaceuti cal use is described. The PEAMMA copolymer layer ensures a sustained releas e of the active agent after oral intake of the granules by the patient. Bec ause of the substantial influence of the copolymer content on the kinetics of the drug release, a reliable method for the PEAMMA quantification had to be developed. The method includes a pre-treatment step, separating the PEA MMA layer from the granule matrix by its selective dissolution in acetone. Employing the pyrolytically formed monomers ethylacrylate and methylmethacr ylate as the target compounds and by means of external calibration, the PEA MMA content of the drug granules was determined with a relative standard de viation of less than 5%. Finally, the Py-GC data obtained from different ba tches of granule material were compared with the corresponding results of k inetic dissolution tests. For one of six samples investigated a too fast dr ug release was found to correlate with a too low PEAMMA content. (C) 1999 E lsevier Science B.V. All rights reserved.