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[Display omitted] • Horizontal conveyor belt filtration was implemented for pharmaceutical separation. • • The process was robust when filtering the aqueous slurry of microcrystalline cellulose. • Suspensions of volatile solvents or large crystals were filtered with high efficacy. • The belt filter was integrated with continuous crystallizers to separate ASA. • Washing reduced impurity content, while residual moisture content remained unaltered. In the pharmaceutical industry, filtration is traditionally carried out in batch mode. However, with the spread of continuous technologies, there is an increasing demand for robust continuous filtration strategies suitable for processing suspensions produced in continuous crystallizers. Accordingly, this study aimed to investigate a lab-scale horizontal conveyor belt filtration approach for pharmaceutical separation purposes for the first time. The newly developed continuous horizontal belt filter (CHBF) was tested under different systems (microcrystalline cellulose (MCC)/water, lactose/ethanol and acetylsalicylic acid (ASA)/water) and diverse conditions. Filtration was robust using a well-defined unimodal particle size distribution MCC in water system, where the residual moisture content varied within narrow limits of 45–52% independently from the process conditions. Besides, the residual moisture content highly depended on the applied solvent and particle size. It could be reduced to below 2% by processing the suspensions of either a volatile solvent (lactose in ethanol) or an aqueous slurry of a large particle size ASA. Finally, the CHBF was connected to a mixed suspension mixed product removal (MSMPR) or a plug flow crystallizer (PFC). The residual moisture content of the CHBF-filtered ASA product and operation characteristics (onset of steady-state) were evaluated in both continuous crystallizer-filter systems. The MSMPR-CHBF system operated with a longer startup period. The size of the in situ-produced crystals was of a similar order magnitude in both systems, resulting in a similar residual moisture content (around 20%). Overall, the tested continuous filter was robust, did not modify the crystal morphology in the examined experimental range, and could be effectively integrated with continuous crystallizers. [ABSTRACT FROM AUTHOR]

[Display omitted] Twin-screw wet granulation (TWSG) is a promising continuous alternative of pharmaceutical wet granulation. One of its benefits is that the components dissolved in the granulation liquid are distributed homogeneously in the granules. This provides an elegant way to manufacture products with ultralow drug doses. Near-infrared (NIR) and Raman spectroscopy are well-established process analytical technology (PAT) tools that can be used for the in-line monitoring of TSWG. However, their detection limit does not enable the measurement of components in the ultralow (i.e. , ppm) range. In this paper, an indirect approach is presented that enables the real-time determination of the concentration of a drug in concentrations between 40 and 100 ppm by using the signal of an excipient, in this case, the polyvinylpyrrolidone (PVP). This component is also dissolved in the granulation liquid; therefore, it is distributed in the same way as the active ingredient. Results of HPLC measurements have proved that the models trained to quantify the concentration of PVP in real-time gave an accurate determination for the active ingredient as well (root mean squared error was 7.07 ppm for Raman and 5.31 ppm for NIR spectroscopy, respectively). These findings imply that it is possible to indirectly predict the concentration of ultralow dose drugs with in-line analytical techniques based on the concentration of an excipient. [ABSTRACT FROM AUTHOR]

The pharmaceutical industry has never seen such a vast development in process analytical methods as in the last decade. The application of near-infrared (NIR) and Raman spectroscopy in monitoring production lines has also become widespread. This work aims to utilize the large amount of information collected by these methods by building an artificial neural network (ANN) model that can predict the dissolution profile of the scanned tablets. An extended release formulation containing drotaverine (DR) as a model drug was developed and tablets were produced with 37 different settings, with the variables being the DR content, the hydroxypropyl methylcellulose (HPMC) content and compression force. NIR and Raman spectra of the tablets were recorded in both the transmission and reflection method. The spectra were used to build a partial least squares prediction model for the DR and HPMC content. The ANN model used these predicted values, along with the measured compression force, as input data. It was found that models based on both NIR and Raman spectra were capable of predicting the dissolution profile of the test tablets within the acceptance limit of the f2 difference factor. The performance of these ANN models was compared to PLS models using the same data as input, and the prediction of the ANN models was found to be more accurate. The proposed method accomplishes the prediction of the dissolution profile of extended release tablets using either NIR or Raman spectra. [ABSTRACT FROM AUTHOR]

[Display omitted] Surface powder sticking in pharmaceutical mixing vessels poses a risk to the uniformity and quality of drug formulations. This study explores methods for evaluating the amount of pharmaceutical powder mixtures adhering to the metallic surfaces. Binary powder blends consisting of amlodipine and microcrystalline cellulose (MCC) were used to investigate the effect of the mixing order on the adherence to the vessel wall. Elevated API concentrations were measured on the wall and within the dislodged material from the surface, regardless of the mixing order of the components. UV imaging was used to determine the particle size and the distribution of the API on the metallic surface. The results were compared to chemical maps obtained by Raman chemical imaging. The combination of UV and VIS imaging enabled the rapid acquisition of chemical maps, covering a substantially large area representative of the analysed sample. UV imaging was also applied in tablet inspection to detect tablets that fail to meet the content uniformity criteria. The results present powder adherence as a possible source of poor content uniformity, highlighting the need for 100% inspection of pharmaceutical products to ensure product quality and safety. [ABSTRACT FROM AUTHOR]