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Hot air drying has proven to be an efficient method to preserve specific edible plant materials with medicinal properties. This is a process involving chemical, physical, and biological changes in plant matrices. Understanding these processes will lead to an improvement in the yields of bioactive compounds. This study aims to optimize the drying process of two species’ fruits used in folk medicine, Berberis vulgaris and Crataegus monogyna. The optimized extracts’ antioxidant capacity was assessed using various assays, with the barberry extract showing very good activity (50.85, 30.98, and 302.45 mg TE/g dw for DPPH, TEAC, and FRAP assays, respectively). Both species exerted good fungal α-glucosidase inhibitory activity (IC50 = 0.34 and 0.56 mg/mL, respectively) but no activity on mammalian α-glucosidase. Additionally, this study identified and quantified the main bioactive compounds. The results presented herein are a breakthrough in industrializing this drying process. Additional studies are necessary to mechanistically understand the drying process involved in these plant materials. This work was supported by a grant of the Romanian Ministry of Education and Research, CNCS–UEFISCDI, project number PN-III-P2-2.1-PED-2019-5360.The authors are grateful to the Foundation for Science and Technology (FCT; Portugal) for financial support through national funds FCT/MCTES to CIMO (UIDB/00690/2020), the national funding for F.C.T. and P.I. and through the institutional scientific employment program contract for M.I.D., and L.B. The authors are grateful to FEDER—Interreg España—Portugal programme for financial support through the project TRANSCoLAB 0612_TRANS_CO_LAB_2_P. info:eu-repo/semantics/publishedVersion

The study focused on the fluid-bed granulation process of a product with two active pharmaceutical ingredients, intended for coated tablets preparation and further transfer to industrial scale. The work aimed to prove that an accurate control of the critical granulation parameters can level the input material variability and offer a user-friendly process control strategy. Moreover, an in-line Near-Infrared monitoring method was developed, which offered a real time overview of the moisture level along the granulation process, thus a reliable supervision and control process analytical technology (PAT) tool. The experimental design's results showed that the use of apparently interchangeable active pharmaceutical ingredients (APIs) and filler sorts that comply with pharmacopoeial specifications, lead to different end-product critical attributes. By adapting critical granulation parameters (i.e. binder spray rate and atomising pressure) as a function of material characteristics, led to granules with average sizes comprised in a narrow range of 280–320 µm and low non-granulated fraction of under 5%. Therefore, the accurate control of process parameters according to the formulation particularities achieved the maintenance of product within the design space and removed material related variability. To complete the Quality by design (QbD) strategy, despite its limited spectral domain, the microNIR spectrometer was successfully used as a robust PAT monitoring tool that offered a real time overview of the moisture level and allowed the supervision and control of the granulation process., Graphical abstract Image, graphical abstract

In the present study, a Quality by Design (QbD) approach was applied in order to develop and optimize a chitosan film formulation loaded with bioactive compounds, intended for further use as an aid in the acceleration of wound healing. Chitosan was chosen as film forming polymer, polyethylene glycol was used as plasticizer, while polyvinyl alcohol was added to improve the bioadhesive properties of the films. Risk assessment strategy was applied to identify the critical formulation variables, which were further introduced as factors of a 3 level Box Behnken design of experiments. The optimal film formulation registered a film thickness of 0.09 mm, solubility in water of 44.9% and a high swelling degree of 2157.4%. The optimized formulation, as well as a placebo formulation without bioactive compounds proved to have a good antibacterial activity. We conclude that in the current study, the QbD approach was successfully applied in order to ensure a good understanding of the manufacturing process, as well as to optimize the formulation of chitosan films. To the best of our knowledge, this is the first time when a QbD approach has been applied in order to develop and optimize a film formulation as a novel wound dressing material.

Solidago virgaurea L. is a perennial plant used in European traditional medicine as a diuretic or a remedy for inflammatory conditions of the urinary tract but also for gout, especially in the Balkans. The present study was focused on a preclinical, in vivo evaluation of antihyperuricemic, anti-inflammatory, and antihypertensive effects of a dry extract from S. virgaurea L. (ESV). Colorimetric and HPLC–MS techniques were used to identify the main chemical constituents of ESV. Antihyperuricemic effect of ESV was assessed in a rat model of hyperuricemia induced by the administration of potassium oxonate. Antihypertensive effect of ESV was evaluated in hyperuricemic rats by monitoring systolic blood pressure with a non-invasive blood-pressure recording system. The anti-inflammatory effect of ESV was tested using a rat model of paw edema. The main chemical constituents of ESV were rutin and phenolic acids represented by chlorogenic and caffeic acid. ESV demonstrated significant antihyperuricemic effects in rats due to an uricosuric mechanism. Additionally, ESV reduced the progression of arterial hypertension in hyperuricemic rats and also showed anti-inflammatory properties slightly inferior to diclofenac. The results suggest that ESV could be a natural remedy for the treatment of gout and protection against endothelial dysfunction caused by hyperuricemia.

Nowadays, it is very important to identify the traditional uses of different plants and to create the context in which new cultural or economic value is given to local resources. In this study, two wild fruits traditionally harvested in autumn in Romania were selected to investigate the effects of drying conditions on the chemical compositions and bioactivities exerted by the extracts and to select the best conditions in terms of air temperature and time of drying. The extracts obtained were assessed in terms of antioxidant capacity and enzyme inhibitory activity, and their main bioactive compounds were identified and quantified. The data presented in this article represent a step forward in applying this process on an industrial-scale.

(1) Background: Portable NIR spectrometers gain more and more ground in the field of Process Analytical Technology due to the easy on-site flexibility and interfacing versatility. These advantages that originate from the instrument miniaturization, also come with a downside with respect to performance compared to benchtop devices. The objective of this work was to evaluate the performance of MicroNIR in a pharmaceutical powder blend application, having three active ingredients and 5 excipients. (2) Methods: Spectral data was recorded in reflectance mode using static and dynamic acquisition, on calibration set samples developed using an experimental design. (3) Results: The developed method accurately predicted the content uniformity of these complex mixtures, moreover it was validated in the entire calibration range using ±10% acceptance limits. With respect to at-line prediction, the method presented lower performance compared to a previously studied benchtop spectrometer. Regarding the in-line monitoring of the blending process, it was shown that the spectral variability-induced by dynamic acquisition could be efficiently managed using spectral pre-processing. (4) Conclusions: The in-line process monitoring resulted in accurate concentration profiles, highlighting differences in the mixing behaviour of the investigated ingredients. For the low dose component homogeneity was not reached due to an inefficient dispersive mixing.

The aim of this work was to develop and validate a NIR method for the quantification of three active ingredients from powder blends. Calibration set formulations were selected based on a D-optimal experimental design with three factors (ibuprofen, paracetamol, caffeine) and five variation levels (80–90–100–110–120%). NIR spectra were recorded in transmittance mode using a rotating sample configuration. Prior to model development the effect of spectral pre-processing was assessed by evaluating its impact over the transfer of orthogonality from concentration space to spectral space. NIR method was validated on the full calibration range with external prediction sets, using the accuracy profile approach. Robustness testing results showed that the accuracy of predictions for the analyte found in lower concentrations (caffeine) was influenced by relative humidity, while paracetamol/ibuprofen predictions were robust to all factors. Redefinition of interfering factor variation level was beneficial to reduce the bias in caffeine content predictions. Also, alternative solutions are provided for ensuring robustness and successful routine use.

The current study aimed to develop carbomer based hydrogel dressings, incorporating ethanolic extracts of Rosmarinus officinalis aerial parts, Achillea millefolium and Calendula officinalis flowers. The pharmaceutical properties of the obtained hydrogels, as well as their texture and antimicrobial activity, were further evaluated. Five wound dressing formulations based on carbopol were prepared. The addition of the ethanolic extracts to the formulation slightly lowered the pH of the hydrogels, as expected. The Rosmarinus officinalis aerial parts extract loaded hydrogel proved to be the firmest one. In terms of consistency and viscosity, the behavior of the five hydrogels was relatively similar. Based on the texture analysis, the texture of the hydrogels has been affected to some extent by the addition of the ethanolic extracts, decreasing their consistency, firmness, and adhesiveness. The hydrogel loaded with Rosmarinus officinalis aerial parts extract and the one incorporating the blend of extracts (mixture of the three above-mentioned extracts) proved to have a good antimicrobial activity. The studied hydrogel formulations could serve as a basis for the development of novel wound dressing materials, although more extended in vivo studies would be needed in order to support current results.

The present work aimed to develop near-infrared (NIR) methods for the in-line monitoring of the powder blending process and off-line prediction of paliperidone tablets quality attributes. The powder blending monitoring method was developed for a Y-shaped mixing equipment, with the spectrometer attached to the filling port and remotely controlled, assuring that the NIR sensor was covered in powder every time spectra were recorded. The method was calibrated by using a set of five different formulations corresponding to a paliperidone content ranging from 60 to 140% of the expected product content. Based on the recorded data, a Partial Least Squares method has been developed taking into account the domain between 1350 and 1550nm of the 1st Savitzky-Golay derivatised spectra, with a low root mean square error of cross-validation of 6.7, offering a real time overview of the homogenisation process. The second part of the study was focused on the calibration and validation of NIR methods for the prediction of paliperidone content and resistance to crushing (hardness) of tablets. Both calibration strategies involved using samples with five levels of variation, 80 to 120% of the target drug concentration and hardness, respectively. The methods were validated by using three level datasets, 90 to 110% of the property of interest. The obtained results were promising, with measured vs. predicted recoveries of over 97.2% for paliperidone content and over 96.3% for tensile strength, values well within the tolerance limits. The in-line blending monitoring allowed a good process overview, enabling the establishment of the process end point, while the noninvasive assay of the tablets quality attributes granted an adequate end product.

The main objective of the present study was to apply QbD methodology in the development of once-a-day sustained release quetiapine tablets. The quality target product profile (QTPP) was defined after the pharmaceutical properties and kinetic release of the innovator product, Seroquel XR 200 mg. For the D-optimal experimental design, the level and ratio of matrix forming agents and the type of extragranular diluent were chosen as independent inputs, which represented critical formulation factors. The critical quality attributes (CQAs) studied were the cumulative percentages of quetiapine released after certain time intervals. After the analysis of the experimental design, optimal formulas and the design space were defined. Optimal formulas demonstrated zero-order release kinetics and a dissolution profile similar to the innovator product, with f2 values of 74.53 and 83.74. It was concluded that the QbD approach allowed fast development of sustained release tablets with similar dissolution behavior as the innovator product.

The present study aimed, on the one hand, to improve the yield of microwave assisted extraction (MAE) of polyphenols from beech bark by using a design of experiments (DoE) approach. On the other hand, beech bark extracts (BBE) were characterized in terms of their phytochemical profile and evaluated for biological potential (antioxidant, antibacterial, antifungal, antimutagen, anti-&alpha, glucosidase, and anti-tyrosinase). The extraction time varies with the amount of extracted total phenolic content (TPC). The microwave power favors TPC extraction but in different proportions. The optimum conditions which gave the highest TPC (76.57 mg GAE/g dry plant material) were reached when the microwave power was 300 W, extraction time was 4 min, and the solvent was an ethanol&ndash, water (50:50) mixture. The practical value of TPC after a controlled experiment was 76.49 mg GAE/g plant material. The identified compounds were vanillic acid, gallic acid, epicatechin, catechin, protocatechuic acid, chlorogenic acid, ferulic acid, and isoquercitrin. The antioxidant potential of BBEs was demonstrated by in vitro experiments. The BBEs were active against Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella typhimurium, Escherichia coli, and Candida species. All extracts were antimutagenic and expressed an inhibition on &alpha, glucosidase and tyrosinase activity. Regarding antimutagen activity, the assayed extracts may be considered to have low or no antimutagen effects.

Nowadays, it is very important to identify the traditional uses of different plants and to create the context in which new cultural or economic value is given to local resources. In this study, two wild fruits traditionally harvested in autumn in Romania were selected to investigate the effects of drying conditions on the chemical compositions and bioactivities exerted by the extracts and to select the best conditions in terms of air temperature and time of drying. The extracts obtained were assessed in terms of antioxidant capacity and enzyme inhibitory activity, and their main bioactive compounds were identified and quantified. The data presented in this article represent a step forward in applying this process on an industrial-scale. This journal is This work was supported by a grant of the Romanian Ministry of Education and Research, CNCS – UEFISCDI, project number PN-III-P1-1.1-PD-2019-1245, within PNCDI III”. The authors are grateful to the Foundation for Science and Technology (FCT, Portugal) for financial support through national funds FCT/ MCTES to CIMO (UIDB/00690/2020); the national funding by FCT, P. I., through the institutional scientific employment program-contract for L. Barros, Maria Inês Dias and C. Pereira’s contracts; to FEDER-Interreg España-Portugal programme through the project TRANSCoLAB 0612_TRANS_CO_LAB_2_P; European Regional Development Fund (ERDF) through the Regional Operational Program North 2020, within the scope of Project Norte-01-0145-FEDER-000042: GreenHealth. info:eu-repo/semantics/publishedVersion

Delayed wound healing is a major complication of diabetes and the medical treatment of such wounds still remains a challenge. Among the modern wound dressings, film dressings are considered to be one of the major advances in wound management. In the current study, the feasibility of using a previously developed and optimized bioactive compounds-loaded chitosan film formulation as a functional wound dressing material for diabetic wounds was investigated. The antioxidant capacity, as well as the effect of the chitosan films on cell viability was assessed in vitro. Furthermore, the in vivo performance of the films was further evaluated, by using a streptozotocin-induced diabetic rat model. The chitosan film formulation provided a beneficial moist wound environment, reducing the risk of dehydration and favouring the closure of the wounds. Also, it exhibited good antioxidant activity, as well as a proliferative effect and adequate biocompatibility. The in vivo evaluation of the bioactive compounds-loaded chitosan film formulation confirmed that the biofilm stimulated wound contraction and accelerated the wound healing process. The results strongly support that the above mentioned chitosan film seems to be a promising formulation, as well as a potential and novel biomaterial used for wound healing applications.

The main objective of the present study was to apply QbD methodology in the development of once-a-day sustained release quetiapine tablets. The quality target product profile (QTPP) was defined after the pharmaceutical properties and kinetic release of the innovator product, Seroquel XR 200 mg. For the D-optimal experimental design, the level and ratio of matrix forming agents and the type of extragranular diluent were chosen as independent inputs, which represented critical formulation factors. The critical quality attributes (CQAs) studied were the cumulative percentages of quetiapine released after certain time intervals. After the analysis of the experimental design, optimal formulas and the design space were defined. Optimal formulas demonstrated zero-order release kinetics and a dissolution profile similar to the innovator product, with f2 values of 74.53 and 83.74. It was concluded that the QbD approach allowed fast development of sustained release tablets with similar dissolution behavior as the innovator product.