Berginc Katja , Huzjak Tilen, Lavrič Olivera, Buzeti Uroš, Jordan Vanja, Velušček Dejan
Characterization of drug release from modified-release products in the presence of alcohol is required to evaluate the possibility of dose dumping due to safety assurance reasons. A generic product containing BCS IV drug and HPMCAS polymer was formulated as amorphous solid dispersion with hot-melt extrusion having the same qualitative and quantitative composition as the reference product. Although formulations were bioequivalent, they exerted different vulnerability towards ethanol, and the root cause was sought to establish appropriate control during product life cycle. To identify critical process parameters (CPPs) and critical material attributes (CMAs) according to the Quality by Design, a systematic screening of excipient properties and process parameters was performed. The indepth evaluation revealed that dose dumping could be avoided with appropriate selection of specification limits for binder viscosity and particle size, specific surface area of the glidant and adjustments in the milling and tableting parameters. Due to the effective prevention of dose dumping, additional changes in qualitative or quantitative composition of the generic product were not required; thus subsequent bioequivalence study was not warranted.
Keywords:Dose-Dumping; Critical Material Attributes; Critical Process Parameters; Microfluxtm; Bioequivalence; Hot-Melt Extrusion
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