Real-time monitoring of granule properties during high shear wet granulation by near-infrared spectroscopy with a chemometrics approach

Abstract

We developed an in-line near-infrared spectroscopy (NIRS) monitoring method enabling a rapid and noninvasive analysis of granule properties during the high shear wet granulation (HSWG) process. Eleven batches were manufactured and used as the calibration dataset and an additional batch was manufactured and used as the validation dataset. The HSWG process was directly monitored using an acousto-optical tunable filter (AOTF)-NIR spectrometer and the NIR spectra related to the physical and chemical changes of the granules were acquired. The particle size, tapped density, bulk density, and powder flowability of the granules were qualitatively and quantitatively evaluated by a chemometrics approach. Principal component analysis (PCA) and partial least square regression (PLSR) were applied for the qualitative and quantitative modelling of the granule properties. The PCA score plots showed a clear relationship between the granule properties and the granulation progress and provided an effective means for the endpoint determination of the manufacturing process. The PLSR models constructed for the quantitative evaluation of the granule properties were demonstrated to be predictive with high accuracy. These findings allow HSWG to be monitored in-line and controlled effectively. A better understanding of the process by NIRS with chemometrics will contribute to developing high-quality drug products using the required quality-by-design approach.

Partial Least Squares Regression-Based Robust Forward Control of the Tableting Process

“…The tapped density was the density after the tapping. The flowability of the granules was evaluated by the Hausner ratio and Carr index [27].…”

An Investigation through the Pharmacotechnical Factors-to Develop a Method to Replace a Super Disintegrant in an Immediate Release Tablet

“…The granules were prepared based on the above design using Flurbiprofen (1mg), PVP K 30, lactose by wet granulation method and lubricated with talc (0.5%) and magnesium stearate (1%). 7 To study the exact effect of particle size on disintegration time the tablets were prepared without disintegrants. The granules were prepared for a batch size for 1000 tablets of 100mg.…”

Particles Size Estimation of Polydopamine Based Polymeric Nanoparticles Using Near-Infrared Spectroscopy Combined with Linear Regression Method

“…The accuracy of the nanostructures size and morphology is primordial for biomedical application [12], thus a set of prepared PDANS of multiple particles size was prepared and analysed for computational modelling using near infrared spectroscopy. The NIRS spectra of polymeric nanoparticles is considered as a response of the inherent absorption properties caused by its chemical component such chemical structure or analyte ratio and scattering phenomena related to its physical characteristics such as particles' size and morphology [1] [2]. The NIRS spectral data are complex and need further chemometrics methods for extraction and interpretation of the desired information [3] [9].…”

“…NIRS is known as a rapid and nondestructive analytical method with no sample preparation [2]. The sensitivity of NIRS spectral signals to any physical factors including particle size, the crystallinity ratio, solid surface roughness, coating thickness, temperature [1] [3] [4] [5] [6] [7] and chemical parameters such as analytes ratio, moisture ratio [8], concentrations and chemical composition; the ingredient distribution [9] could be of great interest in order to understand and evaluate new designed DDS.…”

“…Near-Infrared Spectroscopy (NIRS) (780 -2595 nm), is a noninvasive and eco-friendly analytical technique that presents a promising alternative for cargoes delivery system (DDS) qualitative and quantitative analysis [1] [2]. NIRS is known as a rapid and nondestructive analytical method with no sample preparation [2].…”