Exposing Profound Screening Potential of Ethanol-Based Dissolution Media in the Development of Oral-Modified Dosage Forms
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.
Download the full article as PDF here Exposing Profound Screening Potential of Ethanol-Based Dissolution Media in the Development of Oral-Modified Dosage Forms
Materials
Excipients for extragranular phase were purchased from DuPont (microcrystalline cellulose – MCC), Ashland (hydroxypropylcellulose – HPC), DuPont (croscarmellose sodium -CCS ), Grace GmbH (silicon dioxide) and Peter Greven (magensium stearate). HPMCAS was purchased from Ashland. Silicon dioxide was from Grace GMBH. Salts for dissolution media and solvents were of analytical grade (HCl, octanol, NaCl, NaH2 PO4, NaOH) and were sourced from Merck KGaA, Germany, ethanol 96 % was sourced from Győr Distillery & Refinery Co., Hungary. SIF powder
for FaSSIF media was from Biorelevant, United Kingdom. Drug quantification was performed with UV on MicrofluxTM
apparatus at 256 – 276 nm. HPLC quantification was performed for dissolution experiments; the method used was validated.
Katja B, Tilen H, Olivera L, et al. (2022) Exposing Profound Screening Potential of Ethanol-Based Dissolution Media in the Development of Oral-Modified Dosage Forms. Int J Drug Dev Res J, Vol. 14 No. 11: 979. It Medical Team, https://www.itmedicalteam.pl/
Read more on Magnesium Stearate as a pharmaceutical excipient here:
