Monitoring of multiple solvent induced form changes during high shear wet granulation and drying processes using online Raman spectroscopy

Process Analytical Technology Tools for Monitoring Pharmaceutical Unit Operations: A Control Strategy for Continuous Process Verification

“…Moreover, it provides both quantitative and qualitative data, enabling accurate and consistent monitoring and control during real-time processes. Depending on the compound, the Raman spectrum for a specific molecule differs for each movement of the scattered photon energy, and because it has a unique fingerprint, it enables the monitoring of qualitative information [ 8 , 159 ]. Furthermore, it can be used for analyzing liquid products without moisture interference, similar to Fourier-transform infrared spectroscopy (FTIR) or NIRS, and has a high measurement speed.…”

“…Similar to other spectroscopy methods, Raman spectroscopy is commonly used as a real-time monitoring tool for CPV in various pharmaceutical unit processes, including blending, granulation, coating, and tableting. It can analyze the IQAs and CQAs of drug content [ 160 , 161 , 162 ] during the blending process, moisture content [ 8 , 9 ] during the drying and granulation process, and coating thickness and content [ 157 , 163 , 164 ] during the coating process, as well as enable polymorph identification in API preparation [ 165 , 166 , 167 ], granule-formulation analysis [ 8 ], blending uniformity [ 27 , 168 ], particle-size analysis [ 16 , 159 , 169 ], and others.…”

“…Because it has a high resolution and mass accuracy, it is also used in the qualitative analysis of small molecules and is often selected and used in biological processes, such as in analyzing heterogeneous biomolecules [ 177 , 178 , 179 ]. In addition, it provides quick analysis when high throughput sample preparation and automated data processing are possible [ 8 ]. The mass spectrum is commonly employed to obtain the identity of two compounds or to establish the structure of a new compound and provides the accurate molecular weight or molecular formula to indicate the existence of a specific structural unit in a molecule.…”

“…QbD is defined in ICH Q8 guidelines as “a systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management.” The development of a QbD-based pharmaceutical process involves a scientific risk-based systematic method to correlate critical process parameters (CPPs), input-materials attributes, and critical-quality attributes (CQAs) [ 3 ]. In general, QbD tools, including design of experiments (DoE), empirical modeling, and response surface analysis can develop a design space and reveal process variability during the pharmaceutical manufacturing process [ 7 , 8 , 9 ]. Unlike the existing quality by testing (QbT) system, in which the quality test of the finished product is mainly used, the QbD approach enables drug-quality management to enhance the quality of drugs based on science- and risk-based technology.…”

Improved Understanding of the High Shear Wet Granulation Process under the Paradigm of Quality by Design Using Salvia miltiorrhiza Granules

“…For example, hydroxy propyl methyl cellulose (HPMC) and polyvinyl pyrrolidone (PVP) are commonly used in the chemical drug granulation process [48,49]. However, most APIs of chemical drugs in solid dosage forms are obtained through chemical synthesis or biosynthesis [50]. The viscosities of these APIs are very poor.…”