Calibration transfer of a Raman spectroscopic quantification method for the assessment of liquid detergent compositions from at-line laboratory to in-line industrial scale.

Calibration transfer or standardisation aims at creating a uniform spectral response on different spectroscopic instruments or under varying conditions, without requiring a full recalibration for each situation. In the current study, this strategy is applied to construct at-line multivariate calibration models and consequently employ them in-line in a continuous industrial production line, using the same spectrometer. Firstly, quantitative multivariate models are constructed at-line at laboratory scale for predicting the concentration of two main ingredients in hard surface cleaners. By regressing the Raman spectra of a set of small-scale calibration samples against their reference concentration values, partial least squares (PLS) models are developed to quantify the surfactant levels in the liquid detergent compositions under investigation. After evaluating the models performance with a set of independent validation samples, a univariate slope/bias correction is applied in view of transporting these at-line calibration models to an in-line manufacturing set-up. This standardisation technique allows a fast and easy transfer of the PLS regression models, by simply correcting the model predictions on the in-line set-up, without adjusting anything to the original multivariate calibration models. An extensive statistical analysis is performed in order to assess the predictive quality of the transferred regression models. Before and after transfer, the R2 and RMSEP of both models is compared for evaluating if their magnitude is similar. T-tests are then performed to investigate whether the slope and intercept of the transferred regression line are not statistically different from 1 and 0, respectively. Furthermore, it is inspected whether no significant bias can be noted. F-tests are executed as well, for assessing the linearity of the transfer regression line and for investigating the statistical coincidence of the transfer and validation regression line. Finally, a paired t-test is performed to compare the original at-line model to the slope/bias corrected in-line model, using interval hypotheses. It is shown that the calibration models of Surfactant 1 and Surfactant 2 yield satisfactory in-line predictions after slope/bias correction. While Surfactant 1 passes seven out of eight statistical tests, the recommended validation parameters are 100% successful for Surfactant 2. It is hence concluded that the proposed strategy for transferring at-line calibration models to an in-line industrial environment via a univariate slope/bias correction of the predicted values offers a successful standardisation approach.

Calibration transfer of a Raman spectroscopic quantification method for the assessment of liquid detergent compositions between two at-line instruments installed at two liquid detergent production plants.

Calibration transfer of partial least squares (PLS) quantification models is established between two Raman spectrometers located at two liquid detergent production plants. As full recalibration of existing calibration models is time-consuming, labour-intensive and costly, it is investigated whether the use of mathematical correction methods requiring only a handful of standardization samples can overcome the dissimilarities in spectral response observed between both measurement systems. Univariate and multivariate standardization approaches are investigated, ranging from simple slope/bias correction (SBC), local centring (LC) and single wavelength standardization (SWS) to more complex direct standardization (DS) and piecewise direct standardization (PDS). The results of these five calibration transfer methods are compared reciprocally, as well as with regard to a full recalibration. Four PLS quantification models, each predicting the concentration of one of the four main ingredients in the studied liquid detergent composition, are aimed at transferring. Accuracy profiles are established from the original and transferred quantification models for validation purposes. A reliable representation of the calibration models performance before and after transfer is thus established, based on ß-expectation tolerance intervals. For each transferred model, it is investigated whether every future measurement that will be performed in routine will be close enough to the unknown true value of the sample. From this validation, it is concluded that instrument standardization is successful for three out of four investigated calibration models using multivariate (DS and PDS) transfer approaches. The fourth transferred PLS model could not be validated over the investigated concentration range, due to a lack of precision of the slave instrument. Comparing these transfer results to a full recalibration on the slave instrument allows comparison of the predictive power of both Raman systems and leads to the formulation of guidelines for further standardization projects. It is concluded that it is essential to evaluate the performance of the slave instrument prior to transfer, even when it is theoretically identical to the master apparatus.

Thermoplastic polyurethane-based intravaginal rings for prophylaxis and treatment of (recurrent) bacterial vaginosis.

The aim of the present study was to develop thermoplastic polyurethane (TPU)-based intravaginal rings (IVRs) for prophylaxis and treatment of bacterial vaginosis via hot melt extrusion/injection molding. Therefore, different TPU grades were processed in combination with lactic acid or metronidazole, targeting a sustained lactic acid release over a 28day-period and sustained metronidazole release over 4-7days. Hot melt extrusion of lactic acid/TPU combinations required a lower extrusion temperature due to the plasticizing properties of lactic acid, evidenced by the lower glass transition temperature (Tg) and cross-over point (Ttanδ=1) values. NIR-chemical imaging data showed a homogenous distribution of lactic acid in TPU matrices at drug loads up to 30% (w/w). The addition of metronidazole did not lower processing temperatures, as the active pharmaceutical ingredient remained crystalline in the TPU matrix. Hydrophobic TPUs with a low ratio between the soft and hard segments (SS/HS ratio) in the polymer structure were suitable carriers for the lactic acid-eluting device over a 28-day period, while hydrophilic TPUs were needed to achieve the required release rate of metronidazole-eluting IVRs. IVRs manufactured with a TPU grade having a higher SS/HS ratio and lactic acid/TPU ratio exhibited a more elastic behavior. The addition of 25% (w/w) metronidazole did not affect the mechanical properties of the IVRs. Hydrophilic TPUs were most prone to biofilm formation by Candida albicans and Staphylococcus aureus, but the incorporation of metronidazole in the device prevented biofilm formation. Based on the drug eluting performance and mechanical tests, a mixture of lactic acid and Tecoflex™ EG-93A (20/80, w/w) and a combination of metronidazole and Tecophilic™ SP-93A-100 (25/75, w/w) were selected to design IVRs for the prophylaxis and treatment of bacterial vaginosis, respectively. Slug mucosal irritation tests predicted low irritation potency for both devices.

Calibration transfer of a Raman spectroscopic quantification method from at-line to in-line assessment of liquid detergent compositions.

The industrial production of liquid detergent compositions entails delicate balance of ingredients and process steps. In order to assure high quality and productivity in the manufacturing line, process analytical technology tools such as Raman spectroscopy are to be implemented. Marked chemical specificity, negligible water interference and high robustness are ascribed to this process analytical technique. Previously, at-line calibration models have been developed for determining the concentration levels of the being studied liquid detergents main ingredients from Raman spectra. A strategy is now proposed to transfer such at-line developed regression models to an in-line set-up, allowing real-time dosing control of the liquid detergent composition under production. To mimic in-line manufacturing conditions, liquid detergent compositions are created in a five-liter vessel with an overhead mixer. Raman spectra are continuously acquired by pumping the detergent under production via plastic tubing towards a Raman superhead probe, which is incorporated into a metal frame with a sapphire window facing the detergent fluid. Two at-line developed partial least squares (PLS) models are aimed at transferring, predicting the concentration of surfactant 1 and polymer 2 in the examined liquid detergent composition. A univariate slope/bias correction (SBC) is investigated, next to three well-acknowledged multivariate transformation methods: direct, piecewise and double-window piecewise direct standardization. Transfer is considered successful when the magnitude of the validation sets root mean square error of prediction (RMSEP) is similar to or smaller than the corresponding at-line prediction error. The transferred model offering the most promising outcome is further subjected to an exhaustive statistical evaluation, in order to appraise the applicability of the suggested calibration transfer method. Interval hypothesis tests are thereby performed for method comparison. It is illustrated that the investigated transfer approach yields satisfactory results, provided that the original at-line calibration model is thoroughly validated. Both SBC transfer models return lower RMSEP values than their corresponding original models. The surfactant 1 assay met all relevant evaluation criteria, demonstrating successful transfer to the in-line set-up. The in-line quantification of polymer 2 levels in the liquid detergent composition could not be statistically validated, due to the poorer performance of the at-line model.

Development and validation of an at-line fast and non-destructive Raman spectroscopic method for the quantification of multiple components in liquid detergent compositions.

Implementation of process analytical technology (PAT) tools in the manufacturing process of liquid detergent compositions should allow fast and non-destructive evaluation of the product quality. The aim of this study was to develop and validate a rapid method for quantifying the chemical compounds of five washing liquid precursors. Raman spectroscopy was applied in combination with a two-step multivariate modeling procedure. In first instance, a SIMCA (Soft Independent Modeling of Class Analogy) model was developed and validated, allowing the distinction between the different laundry detergents. Once the product was correctly identified, it was aimed at predicting the concentration of its individual components using partial least squares (PLS) models. Raman spectra were collected at-line with a total acquisition time of 20 s, using a non-contact fiber-optic probe. The SIMCA model was perfectly capable of differentiating between the classes of the laundry liquid precursors. Per detergent, the concentration of at least three main ingredients could be predicted with a recovery between 98% and 102% and a standard deviation below 2.5%. Accuracy profiles based on the analysis results of validation samples were then calculated to prove the reliability of the developed regression models. ß-expectation tolerance intervals were calculated for each model and for each validated concentration level. The acceptance limits were set at 5% relative bias, indicating that at least 95% of future measurements should not deviate more than 5% from the true value. Furthermore, based on the data of the accuracy profiles, the measurement uncertainty was determined. The developed Raman spectroscopic method demonstrated to be able to rapidly and adequately determine the concentration of the components of interest in the liquid detergent compositions at-line.

Quiste meníngeo intraorbitario asociado a tejido cerebeloso heterotópico / Cystic meningeal intraorbitary association tissue cerebrose heterotopy

Presentamos el caso de una niña de 14 meses con colomboma coroideo bilateral y proptosis paraaxial progresiva del ojo izquierdo, en la que se halló un quiste meníngeo en la órbita izquierda con tejido cerebeloso ectópico. La lesión se resolvió hallar otros dos casos similares en la literatura, describiendo tejido cerebeloso ectópico en la órbita

Quiste meníngeo intraorbitario asociado a tejido cerebeloso heterotópico / Cystic meningeal intraorbitary association tissue cerebrose heterotopy

Presentamos el caso de una niña de 14 meses con colomboma coroideo bilateral y proptosis paraaxial progresiva del ojo izquierdo, en la que se halló un quiste meníngeo en la órbita izquierda con tejido cerebeloso ectópico. La lesión se resolvió hallar otros dos casos similares en la literatura, describiendo tejido cerebeloso ectópico en la órbita

La importancia de la RNM dinámica en el estudio y detección de fístulas LCR post TEC grave / The importance of RNM dinamic at the detection and study of LCR fistula post TEC severe

El TEC representa un grave problema en la salud pública constituyendo la primer causa de muerte en menores de 45 años, surgiendo en la población que sobrevive complicaciones relacionadas con desgarros durales y/o fístulas de LCR (4-8 por ciento). Presentamos tres pacientes con TEC grave cuya complicación fue la infección alejada (miningitis a Diplococo Pneumoniae), sospechándose una comunicacción anormal entre cavidades sinusales con endocráneo en quienes evaluamos los estudios de diagnóstico por imágenes para la detección de fístulas de LCR post TEC grave, diagnosticándola en todos mediante RNM Cisternográfica dinámiva. Los hallazgos mencionados fueron correlacionados con los hallazgos quirúrgicos, por lo que el método presentó una sensibilidad y especificidad del 100 por ciento para el diagnóstico de fístulas de LCR. Creemos que este método, aunado con la TAC de alta resolución y la asistencia del laboratorio en cuanto a la busqueda de B2 transferrina, disminuyen al minimo las extensas "exploraciones" a ciegas, que frecuentemente resultan infractuosas y desalentadora para el neurocirujano. (AU)

La importancia de la RNM dinámica en el estudio y detección de fístulas LCR post TEC grave / The importance of RNM dinamic at the detection and study of LCR fistula post TEC severe

El TEC representa un grave problema en la salud pública constituyendo la primer causa de muerte en menores de 45 años, surgiendo en la población que sobrevive complicaciones relacionadas con desgarros durales y/o fístulas de LCR (4-8 por ciento). Presentamos tres pacientes con TEC grave cuya complicación fue la infección alejada (miningitis a Diplococo Pneumoniae), sospechándose una comunicacción anormal entre cavidades sinusales con endocráneo en quienes evaluamos los estudios de diagnóstico por imágenes para la detección de fístulas de LCR post TEC grave, diagnosticándola en todos mediante RNM Cisternográfica dinámiva. Los hallazgos mencionados fueron correlacionados con los hallazgos quirúrgicos, por lo que el método presentó una sensibilidad y especificidad del 100 por ciento para el diagnóstico de fístulas de LCR. Creemos que este método, aunado con la TAC de alta resolución y la asistencia del laboratorio en cuanto a la busqueda de B2 transferrina, disminuyen al minimo las extensas "exploraciones" a ciegas, que frecuentemente resultan infractuosas y desalentadora para el neurocirujano.