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In the original publication, there was a mistake in Figure 6 [...]

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.

Diabetic autonomic neuropathy is probably the most undiagnosed but serious complication of diabetes. The main objectives were to assess the prevalence of peripheral and autonomic neuropathy in a population of diabetic patients, analyze it in a real-life outpatient unit scenario and determine the feasibility of performing SUDOSCAN tests together with widely used tests for neuropathy. A total of 33 patients were included in the study. Different scoring systems (the Toronto Clinical Neuropathy Score—TCNS; the Neuropathy Disability Score—NDS; and the Neuropathy Symptom Score—NSS) were applied to record diabetic neuropathy (DN), while the SUDOSCAN medical device was used to assess sudomotor function, detect diabetic autonomic neuropathy and screen for cardiac autonomic neuropathy (CAN). Fifteen (45.5%) patients had sudomotor dysfunction. The SUDOSCAN CAN risk score was positively correlated with the hands’ electrochemical sweat conductance (ESC), diastolic blood pressure (DBP), the level of the glycated hemoglobin, as well as with the TCNS, NDS and NSS. Performing SUDOSCAN tests together with other tests for DN proved to be a feasible approach that could be used in daily clinical practice in order to screen for DN, as well as for the early screening of CAN, before more complex and time-consuming tests.

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.

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.

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.