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► The feasibility of replacing KF for water content testing in bulk powders and tablets with at-line near infrared (NIR) or microwave resonance (MR) methods was demonstrated. ► ...Accurate NIR and MR prediction models were developed with a minimalistic approach to calibration. The NIR method can accurately predict water content in bulk powders in the range of 0.5–5% w/w. ► A general MR method was used to predict water content in two different types of blends.
In this paper we demonstrate the feasibility of replacing KF for water content testing in bulk powders and tablets with at-line near infrared (NIR) or microwave resonance (MR) methods. Accurate NIR and MR prediction models were developed with a minimalistic approach to calibration. The NIR method can accurately predict water content in bulk powders in the range of 0.5–5% w/w. Results from this method were compared to a MR method. We demonstrated excellent agreement of both NIR and MR methods for powders vs. the reference KF method. These methods are applicable to in-process control or quality control environments. One of the aims of this study was to determine if a calibration developed for a particular product could be used to predict the water content of another product (with related composition) but containing a different active pharmaceutical ingredient (API). We demonstrated that, contrary to the NIR method, a general MR method can be used to predict water content in two different types of blends.
Finally, we demonstrated that a MR method can be developed for at-line moisture determination in tablets.
•At-line PAT is used to monitor and control of lamivudine-saccharinate salt synthesis.•MIR with MCR-ALS is applied as at-line PAT to follow the pharmaceutical salt formation.•Concentration profiles ...retrieved by MCR-ALS showed the end of the synthesis process.
This article presents a promising application of Fourier transform-mid infrared (FT-MIR) spectroscopy with multivariate curve resolution ― alternating least-squares (MCR-ALS) as an at-line process analytical technology (PAT) to enhancing the understanding and continuous control of a pharmaceutical manufacturing process. Its objective was to monitor the synthesis of pharmaceutical multicomponent crystals in solid-state, namely the mixture between lamivudine (active pharmaceutical ingredient-API) and saccharin (coformer) using liquid assisted grinding (LAG) in proportion of 1:1 in a ball mill. The continuous monitoring of synthesis procedure ensured product quality, revealing some of the events that can be detected during mechanochemical synthesis by FT-MIR spectroscopy with MCR-ALS. The concentration profiles retrieved by MCR-ALS allowed to identify the end of the salt synthesis. In fact, this is one of the advantages of real-time monitoring using FT-MIR spectroscopy and MCR-ALS, because it can be helpful not only to monitor and control a pharmaceutical manufacturing process, but also to optimize efficient use of energy, time and raw materials for lamivudine-saccharinate salt synthesis. Moreover, it allowed to understand that the antiretroviral lamivudine-saccharinate salt synthetized by LAG showed a fast reaction mechanism due to the presence of ethanol as catalyst. Differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) techniques provided additional information needed to fully characterize pharmaceutical lamivudine-saccharinate salt synthetized by LAG technique.
The aim of this study was to investigate on an industrial scale the potential of multispectral imaging (MSI) in the assessment of the quality of different poultry products. Therefore, samples of ...chicken breast fillets, thigh fillets, marinated souvlaki and burger were subjected to MSI analysis during production together with microbiological analysis for the enumeration of Total Viable Counts (TVC) and
spp. Partial Least Squares Regression (PLS-R) models were developed based on the spectral data acquired to predict the "time from slaughter" parameter for each product type. Results showed that PLS-R models could predict effectively the time from slaughter in all products, while the food matrix and variations within and between batches were identified as significant factors affecting the performance of the models. The chicken thigh model showed the lowest RMSE value (0.160) and an acceptable correlation coefficient (r = 0.859), followed by the chicken burger model where RMSE and r values were 0.285 and 0.778, respectively. Additionally, for the chicken breast fillet model the calculated r and RMSE values were 0.886 and 0.383 respectively, whereas for chicken marinated souvlaki, the respective values were 0.934 and 0.348. Further improvement of the provided models is recommended in order to develop efficient models estimating time from slaughter.
At-line sampling by solid phase microextraction (SPME) followed by GC-MS analysis was investigated as a fast analytical method to identify and quantify the compounds evolved during intermediate ...pyrolysis of biomass. A 75μm carboxen/polidimethylsiloxane (CAR/PDMS) coated fiber in retracted configuration was inserted at-line during pyrolysis at 500°C with a bench scale fixed bed pyrolyzer of different biomass substrates, lignocellulosic feedstock, agricultural wastes, animal residues and algal biomass. The molecular composition resulting from SPME sampling was compared to the chemical composition of collected pyrolysis liquid, which included the aqueous and organic phase (bio-oil). The storage capacity of the SPME fiber was tested 48 and 96h after sampling under air atmosphere and vacuum-packed plastic bags. The SPME-GC-MS profiles could be utilized to gather information on the characteristics of pyrolysis process, such as the efficiency of vapor condensation.
•At-line sampling by solid phase microextraction in a bench scale pyrolysis reactor•SPME vapors evolved during pyrolysis were similar to the resulting pyrolysis liquid.•Application for the monitoring of pyrolysis reactors in the production of bio-oil•Fiber can be stored in tightly closed plastic bags for 4days before GC-MS analysis.
Near infrared reflectance (NIR) spectroscopy was evaluated as at-line technique to predict FA profile of chicken breast directly at the slaughterhouse. Intact breasts of 214 chickens were scanned by ...applying a fiber optic probe to the Pectoralis superficialis muscle. Meat samples were analyzed by gas chromatography as the reference method for the determination of FA composition. Calibration equations were developed considering NIR wavelengths between 1100 and 1830nm, and modified partial least square (MPLS) was chosen as the chemometrics method to perform the calibrations. Different mathematical pre-treatments were tested and the best calibration equation for each FA was retained. Near infrared reflectance spectroscopy did not result in satisfactory predictions of FA. The best predictions were observed for oleic acid (C18:1n-9), monounsaturated FA (MUFA), and polyunsaturated FA (PUFA), and for a few minor FA. Results suggest that for chicken breast muscle, a lean meat, it was not possible to predict FA using NIR spectroscopy as an at-line technique in the abattoir.
Although process analytical technology (PAT) guidance has been introduced to the pharmaceutical industry just a decade ago, this innovative approach has already become an important part of efficient ...pharmaceutical development, manufacturing, and quality assurance. PAT tools are especially important in technologically complex operations which require strict control of critical process parameters and have significant effect on final product quality. Manufacturing of prolonged release film coated pellets is definitely one of such processes. The aim of the present work was to study the applicability of the at-line near-infrared spectroscopy (NIR) approach in the monitoring of pellet film coating and curing steps. Film coated pellets were manufactured by coating the active ingredient containing pellets with film coating based on polymethacrylate polymers (Eudragit® RS/RL). The NIR proved as a useful tool for the monitoring of the curing process since it was able to determine the extent of the curing and hence predict drug release rate by using partial least square (PLS) model. However, such approach also showed a number of limitations, such as low reliability and high susceptibility to pellet moisture content, and was thus not able to predict drug release from pellets with high moisture content. On the other hand, the at-line NIR was capable to predict the thickness of Eudragit® RS/RL film coating in a wide range (up to 40μm) with good accuracy even in the pellets with high moisture content. To sum up, high applicability of the at-line NIR in the monitoring of the prolonged release pellets production was demonstrated in the present study. The present findings may contribute to more efficient and reliable PAT solutions in the manufacturing of prolonged release dosage forms.
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An innovative and automated method for the at-line monitoring of secreted protein was developed by harnessing a Surface Plasmon Resonance-based biosensor to a bioreactor. The proof of concept was ...performed by following at-line the relative concentration of a secreted protein produced by transient transfection of mammalian cells in a bioreactor. Our results suggest that our approach can be readily applied to the at-line determination of both protein concentration and bioactivity. Our experimental setup and strategy can thus satisfy the needs related to the development of novel bioprocess control protocols in the context of the new process analytical technology that arises in the biopharmaceutical industry. Biotechnol. Bioeng. 2008;100: 184-188.
•At-line HSCCC-Sephadex LH-20 CC was firstly developed.•Antioxidants were firstly screened by DPPH-HPLC.•Seven antioxidants were purified from vine tea by the at-line configuration.•Method may be ...extended to other natural products.
Vine tea (Ampelopsis grossedentata), a widely used healthy tea, beverage and herbal medicine, exhibited strong antioxidant activity. However, systematic purification of antioxidants, especially for those with similar structures or polarities, is a challenging work. Here, we present a novel at-line hyphenation of high-speed countercurrent chromatography with Sephadex LH-20 column chromatography (HSCCC-Sephadex LH-20 CC) for rapid and efficient separation of antioxidants from vine tea target-guided by 1,1-diphenyl-2-picryl-hydrazyl radical-high performance liquid chromatography (DPPH-HPLC) experiment. A makeup pump, a six-port switching valve and a trapping column were served as interface. The configuration had no operational time and mobile phase limitations between two dimensional chromatography and showed great flexibility without tedious sample-handling procedure. Seven targeted antioxidants were firstly separated by stepwise HSCCC using petroleum ether–ethyl acetate–methanol–water (4:9:4:9, v/v/v/v) and (4:9:5:8, v/v/v/v) as solvent systems, and then co-eluted antioxidants were on-line trapped, concentrated and desorbed to Sephadex LH-20 column for further off-line purification by methanol. It is noted that six elucidated antioxidants with purity over 95% exhibited stronger activity than ascorbic acid (VC). More importantly, this at-line hyphenated strategy could sever as a rapid and efficient pathway for systematic purification of bioactive components from complex matrix.
The aim of this study was to investigate the effects of the molecular weight (Mw) of hydroxypropyl cellulose (HPC) and grinding duration on solid dispersions (SDs) formation and their ...characteristics. In this study, ternary amorphous SD systems containing curcumin (CUR), HPC, and sodium dodecyl sulfate (SDS) were developed using the milling method and characterized their physicochemical and mechanochemical properties. After 120-min grinding, the particle size reduced to under 1 μm and the GMs totally transformed into amorphous phase. The release behavior of CUR depended on the grade of HPCs due to their Mw and corresponding viscosity. During the SD formation process, the grinding time and Mw of HPC could be monitored by analyzing data obtained from MIR and NIR spectra based on chemometrics. There were two steps in SD formation: (1) simple dispersion with grinding time under 30 min and (2) random dispersion of mixtures with grinding time from 30 to 120 min. The HPC-M (700,000 Da) resulted in more effectively forming SD systems.
Analyzed data of MIR spectra. Display omitted
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