Original research paper. Characterization and taste masking evaluation of microparticles with cetirizine dihydrochloride and methacrylate-based copolymer obtained by spray drying.

Taste of a pharmaceutical formulation is an important parameter for the effectiveness of pharmacotherapy. Cetirizine dihydrochloride (CET) is a second-generation antihistamine that is commonly administered in allergy treatment. CET is characterized by extremely bitter taste and it is a great challenge to successfully mask its taste; therefore the goal of this work was to formulate and characterize the microparticles obtained by the spray drying method with CET and poly(butyl methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl methacrylate 1:2:1 copolymer (Eudragit E PO) as a barrier coating. Assessment of taste masking by the electronic tongue has revealed that designed formulations created an effective taste masking barrier. Taste masking effect was also confirmed by the in vivo model and the in vitro release profile of CET. Obtained data have shown that microparticles with a drug/polymer ratio (0.5:1) are promising CET carriers with efficient taste masking potential and might be further used in designing orodispersible dosage forms with CET.

Influence of dissolution-modifying excipients in various pharmaceutical formulations on electronic tongue results.

The overall performance of a potentiometric electronic tongue (ET) as well as the sensitivity and selectivity pattern of particular ion-selective electrodes forming the array towards exemplary APIs (metamizole sodium, pseudoephedrine sulphate) and excipients (hypromellose, carmellose, Eudragit E) was determined. Simultaneous sensing of both API and the encapsulating excipient in their physical mixture was noticed using potentiometric sensors. Usually, such altering of chemical image is treated as an evidence of taste masking/modified release effect (linked with chemical entrapment of API in polymer matrix), while the observed "mixture effect" can also take place which may complicate the interpretation of ET results. Moreover, the influence of the same excipients on chemical images of various APIs was compared and related to sensor array performance. The presented considerations should be taken into account in the case of ET assessment of drug dissolution profiles and detection of modified release effect, especially when novel drug delivery systems are considered.

Two-dimensional fluorescence as soft sensor in the monitoring of biotransformation performed by yeast.

Soft sensors are powerful tools for bioprocess monitoring due to their ability to perform online, noninvasive measurement, and possibility of detection of multiple components in cultivation media, which in turn can provide tools for the quantification of more than one metabolite/substrate/product in real time. In this work, soft sensor based on excitation-emission fluorescence is for the first time applied for the monitoring of biotransformation production of 2-phenylethanol (2-PE) by yeast strains. Main process parameters-such as optical density, glucose, and 2-PE concentrations-were determined with high accuracy and precision by fluorescence fingerprinting coupled with partial least squares regression. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:299-307, 2017.

Influence of Experimental Conditions on Electronic Tongue Results-Case of Valsartan Minitablets Dissolution.

A potentiometric electronic tongue was applied to study the release of valsartan from pharmaceutical formulations, i.e., minitablets uncoated and coated with Eudragit E. Special attention was paid to evaluate the influence of medium temperature and composition, as well as to compare the performances of the sensor arrays working in various hydrodynamic conditions. The drug dissolution profiles registered with the ion-sensitive electrodes were compared with standard dissolution tests performed with USP Apparatus 2 (paddle). Moreover, the signal changes of all sensors were processed by principal component analysis to visualize the release modifications, related to the presence of the coating agent. Finally, the importance and influence of the experimental conditions on the results obtained using potentiometric sensor arrays were discussed.

Independent comparison study of six different electronic tongues applied for pharmaceutical analysis.

Electronic tongue technology based on arrays of cross-sensitive chemical sensors and chemometric data processing has attracted a lot of researchers' attention through the last years. Several so far reported applications dealing with pharmaceutical related tasks employed different e-tongue systems to address different objectives. In this situation, it is hard to judge on the benefits and drawbacks of particular e-tongue implementations for R&D in pharmaceutics. The objective of this study was to compare the performance of six different e-tongues applied to the same set of pharmaceutical samples. For this purpose, two commercially available systems (from Insent and AlphaMOS) and four laboratory prototype systems (two potentiometric systems from Warsaw operating in flow and static modes, one potentiometric system from St. Petersburg, one voltammetric system from Barcelona) were employed. The sample set addressed in the study comprised nine different formulations based on caffeine citrate, lactose monohydrate, maltodextrine, saccharin sodium and citric acid in various combinations. To provide for the fair and unbiased comparison, samples were evaluated under blind conditions and data processing from all the systems was performed in a uniform way. Different mathematical methods were applied to judge on similarity of the e-tongues response from the samples. These were principal component analysis (PCA), RV' matrix correlation coefficients and Tuckers congruency coefficients.

Electrochemical monitoring of citric acid production by Aspergillus niger.

Hybrid electronic tongue was developed for the monitoring of citric acid production by Aspergillus niger. The system based on various potentiometric/voltammetric sensors and appropriate chemometric techniques provided correct qualitative and quantitative classification of the samples collected during standard Aspergillus niger culture and culture infected with yeast. The performance of the proposed approach was compared with the monitoring of the fermentation process carried out using classical methods. The results obtained proved, that the designed hybrid electronic tongue was able to evaluate the progress and correctness of the fermentation process.

Flow-through sensor array applied to cytotoxicity assessment in cell cultures for drug-testing purposes.

The viability of cells cultured in microsystems for drug screening purposes is usually tested with a variety of colorimetric/fluorescent methods. In this work we propose an alternative way of assessing cell viability-flow-through sensor array that can be connected in series with cell microbioreactors as compatible detection system. It is shown, that the presented device is capable of cytotoxic effect detection and estimation of cell viability after treatment with 1,4-dioxane and 5-fluorouracil, which proves that it can be used for truly non-invasive, fast, reliable, continuous cell culture monitoring in microscale.

Probing an artificial polypeptide receptor library using a series of novel histamine H3 receptor ligands.

An artificial polypeptide receptor (APR) library was created by using the self-organization of N-lipidated peptides attached to cellulose via m-aminophenylamino-1,3,5-triazine. The response of the library was probed using a series of novel H3 receptor ligands. Since no guidelines on how to design an APRs selective vs certain receptor types exist, a diverse set of amino acids (Ala, Trp, Pro, Glu, His, Lys and Ser) were used and coupled with one of three gating fatty acids (palmitic, ricinoleic or capric). A competitive adsorption-desorption of an appropriate reporter dye was used for the indirect visualization of the interactions of guests with particular receptors. The resulted library response to individual inhibitors was then arranged in a matrix, preprocessed and analyzed using the principal component analysis (PCA) and partial least squares (PLS) method. The most important conclusion obtained from the PCA analysis is that the library differentiates the probed compounds according to the lipophilicity of the gating unit. The PC3 with a dominant absolute contribution of the receptors containing Glu allowed for the best separation of the ligands with respect to their activity. This conclusion is in agreement with the fact that Glu 206 is a genuine ligand counterpart in the natural histamine receptor.

Monitoring of beer fermentation based on hybrid electronic tongue.

Monitoring of biotechnological processes, including fermentation is extremely important because of the rapidly occurring changes in the composition of the samples during the production. In the case of beer, the analysis of physicochemical parameters allows for the determination of the stage of fermentation process and the control of its possible perturbations. As a tool to control the beer production process a sensor array can be used, composed of potentiometric and voltammetric sensors (so-called hybrid Electronic Tongue, h-ET). The aim of this study is to apply electronic tongue system to distinguish samples obtained during alcoholic fermentation. The samples originate from batch of homemade beer fermentation and from two stages of the process: fermentation reaction and maturation of beer. The applied sensor array consists of 10 miniaturized ion-selective electrodes (potentiometric ET) and silicon based 3-electrode voltammetric transducers (voltammetric ET). The obtained results were processed using Partial Least Squares (PLS) and Partial Least Squares-Discriminant Analysis (PLS-DA). For potentiometric data, voltammetric data, and combined potentiometric and voltammetric data, comparison of the classification ability was conducted based on Root Mean Squared Error (RMSE), sensitivity, specificity, and coefficient F calculation. It is shown, that in the contrast to the separately used techniques, the developed hybrid system allowed for a better characterization of the beer samples. Data fusion in hybrid ET enables to obtain better results both in qualitative analysis (RMSE, specificity, sensitivity) and in quantitative analysis (RMSE, R(2), a, b).

Potentiometric electronic tongues for foodstuff and biosample recognition--an overview.

Potentiometric sensors are attractive tools for the fabrication of various electronic tongues that can be used in wide area of applications, ranging from foodstuff recognition to environmental monitoring and medical diagnostics. Their main advantages are the ability to modify their selectivity (including cross-sensitivity effects) and the possibility of miniaturization using appropriate construction methods for the transducer part (e.g., with the use of solid-state technology). In this overview various examples of the design, performance, and applications of potentiometric electronic tongues are presented. The results summarize recent research in the field conducted in the Department of Microbioanalytics, Warsaw University of Technology (WUT).

Taste masking of roxithromycin by spray drying technique.

The spray drying technique was used to obtain the roxithromycin containing microcapsules with high taste masking efficiency. Eudragit L30D-55 was chosen as a barrier coating. The taste was evaluated by an electronic tongue, and taste-masking effect in water lasted at least several dozen hours.

Classification of amino acids and oligopeptides with the use of multi-mode chemical images obtained with ion selective electrode array.

The analysis of amino acids and oligopeptides as important bioanalytes is a significant task in medical diagnostics and proteomic research and currently it is based on chromatographic and electrophoretic methods. In this paper, an approach based on sensor array coupled with titration is proposed for effective recognition of 5 amino acids and 4 oligopeptides. It is shown, that the increase of information gained during measurements of sensors' signals in various pH allows for capturing more data on interaction of amino acids and oligopeptides with various polymeric membranes of potentiometric electrodes used in the array, and that leads to the lowering of classification errors in partial least squares analysis.

Electronic tongue for the detection of taste-masking microencapsulation of active pharmaceutical substances.

Electronic tongues can produce chemical images of samples, whose changes can be correlated with general properties, e.g. taste sensations. In this work, a sensor array equipped with eight types of ion-selective electrodes was coupled with Principal Components Analysis in order to detect microencapsulation effect of two Active Pharmaceutical Ingredients (APIs), which influences their taste properties. The character of change of sensor array responses in samples modified by microencapsulation was the same in two investigated APIs (Ibuprofen and Rixithromycin), proving, that the "sensed taste" becomes similar in both formulations after Eudragit modification. The obtained results show, that the presented electronic tongue can be used for analysis of masking effects in drugs and detection of microencapsulation effect.

Monitoring of periodic anaerobic digestion with flow-through array of miniaturized ion-selective electrodes.

In the last few years Electronic tongues (ETs) based on various sensor arrays were applied to the monitoring of various fermentation processes, as devices capable of fast, inexpensive, automated and on-line control. In this work a novel application of ET is proposed--flow-through array of miniaturized ion-selective electrodes (ISEs) was used for the analysis of samples obtained during anaerobic digestion (methane fermentation) performed in periodic conditions. The samples were classified according to their Chemical Oxygen Demand (COD) and Volatile Fatty Acid (VFA) content. Moreover, for this application a novel design of ISEs was developed, which is fully compatible with flow-through modules for sensor measurements.

The monitoring of methane fermentation in sequencing batch bioreactor with flow-through array of miniaturized solid state electrodes.

Electronic tongues (ETs) based on potentiometric sensor arrays are often used for foodstuff classification, origin recognition, estimation of complex samples' properties, etc. In the last few years they were also applied for various fermentation monitoring, such as Aspergillus niger fermentation, light cheese production, batch Escherichia coli fermentation, as a devices capable of fast, inexpensive, automated and on-line control of the process. In this work a novel application for ET is proposed-flow-through array of solid state electrodes was used for the analysis of samples obtained during methane fermentation (anaerobic digestion) of whey in sequencing batch bioreactor, according to their volatile fatty acid (VFA) content and chemical oxygen demand (COD).

Miniaturized tools and devices for bioanalytical applications: an overview.

This article presents an overview of various miniaturized devices and technologies developed by our group. Innovative, fast and cheap procedures for the fabrication of laboratory microsystems based on commercially available materials are reported and compared with well-established microfabrication techniques. The modules fabricated and tested in our laboratory can be used independently or they can be set up in different configurations to form functional measurement systems. We also report further applications of the presented modules e.g. disposable poly(dimethylsiloxane) (PDMS) microcuvettes, fibre optic detectors, potentiometric sensors platforms, microreactors and capillary electrophoresis (CE) microchips as well as integrated microsystems e.g. double detection microanalytical systems, devices for studying enzymatic reactions and a microsystem for cell culture and lysis.

Miniaturized electronic tongue with an integrated reference microelectrode for the recognition of milk samples.

This work presents the application of a new construction of an electronic tongue for the classification of milk originating from various producers. Integrated array of microelectrodes was fabricated from epoxy-glass laminate. PVC membranes with various additives were used as chemosensitive layers. The developed device is capable of recognition of milk samples with high correctness. Moreover, the application of miniaturized reference electrode, integrated on the same substrate, also provided satisfactory results, which can be helpful in future constructions of hand-held electronic tongue systems.

Sensor arrays for liquid sensing--electronic tongue systems.

Electronic tongue systems are multisensor devices dedicated to automatic analysis of complicated composition samples and to the recognition of their characteristic properties. Recently, the number of publications covering this topic has significantly increased. Many possible architectures of such devices were proposed: potentiometric, voltammetric, as well as approaches embracing mass- and optical-sensors. For the analysis of sensor array data, various pattern recognition systems were proposed. All of these topics are summarized in this review. Moreover, additional problems are considered: miniaturization of electronic tongues and hybrid systems for liquid sensing.

Performance of selective and partially selective sensors in the recognition of beverages.

A sensor array composed of selective and partially selective electrodes is applied to the recognition of beverages: milk, orange juice, and beer. The role of selective and partially selective sensors in classification results is discussed. For this reason two experiments are realized: distinguishing among various types of foodstuffs and the recognition of their origin (manufacturer). In both cases, the measurements were performed in stationary and flow mode. Classical ion-selective electrodes and miniaturized solid-state electrodes were considered. The best results are obtained when the two types of sensor are incorporated in the array, which leads to the highest correctness of the system response. It is however worth to notice, that in the case of some samples (for example, milk) satisfactory results were obtained when only selective or when only partially selective electrodes were applied.

The recognition of beer with flow-through sensor array based on miniaturized solid-state electrodes.

Flow-through electronic tongue based on miniaturized solid-state potentiometric sensors has been developed. A simple technique, i.e. membrane solution casting on the surface of the planar Au transducers was applied for the preparation of classical ion-selective and partially selective microelectrodes, introduced in the flow-through sensor array. The performance of the designed electronic tongue was tested in the qualitative analysis of various brands of beer. Samples of the same brand of beer but with different manufacture dates, originating from different manufacture lots, have been applied in the studies. The combination of PLS and ANN techniques allowed the discrimination between different brands of beer with 83% of correct classifications.