Electrospun polylactic acid and polyvinyl alcohol fibers as efficient and stable nanomaterials for immobilization of lipases

Electrospinning was applied to create easy-to-handle and high- surface-area membranes from continuous nanofibers of polyvinyl alcohol (PVA) or polylactic acid (PLA). Lipase PS from Burkholderia cepacia and Lipase B from Candida antarctica (CaLB) could be immobilized effectively by adsorption onto the fibrous material as well as by entrapment within the electrospun nanofibers. The biocatalytic performance of the resulting membrane biocatalysts was evaluated in the kinetic resolution of racemic 1-phenylethanol (rac-1) and 1-phenylethyl acetate (rac- 2). Fine dispersion of the enzymes in the polymer matrix and large surface area of the nanofibers resulted in an enormous increase in the activity of the membrane biocatalyst compared to the non-immobilized crude powder forms of the lipases. PLA as fiber-forming polymer for lipase immobilization performed better than PVA in all aspects. Recycling studies with the various forms of electrospun membrane biocatalysts in ten cycles of the acylation and hydrolysis reactions indicated excellent stability of this forms of immobilized lipases. PLA-entrapped lipases could preserve lipase activity and enantiomer selectivity much better than the PVA-entrapped forms. The electrospun membrane forms of CaLB showed high mechanical stability in the repeated acylations and hydrolyses than commercial forms of CaLB immobilized on polyacrylamide beads (Novozyme 435 and IMMCALB- T2-150). © 2016 Springer-Verlag Berlin Heidelber

The Effect of Surfactants and pH Modifying Agents on the Dissolution and Permeation of Pimobendan

Solubility and permeability are key parameters for establishing in vitro-in vivo correlation for poorly water-soluble active pharmaceutical ingredients (APIs). Recent studies demonstrate that not only solubility, but also effective permeability of the API may change due to the addition of solubilizing agents, and there is a certain mathematical relation between these physicochemical parameters. The aim of this study was to show the importance of early screening of solubility and permeability in presence of additives in order to achieve the expected bioavailability of the API. In this work, the effect of surfactants and microenvironmental pH modifiers were in focus, and pimobendan was chosen as model drug.In the case of pH modifiers, the equilibrium solubility of the API increased, while the permeability decreased significantly. No negative effect was observed for two surfactants at low additive levels, but these two additives also exhibited a slightly negative effect on permeability when used at higher concentrations. In the simultaneous dissolution-permeation studies the surfactants-containing formulation was found to have slightly higher flux than the pH-modifier-containing one. It can be due to the phenomenon that the dissolution of the active substance can be enhanced by these surfactants without any significant permeability reducing effect.The results obtained from the present study clearly demonstrate the importance of studying drug-additive interactions in every step of formulation development and based on these, the selection of the appropriate quality and quantity of additives. In addition, the results also underline the significance of performing simultaneous dissolution-permeation studies to predict bioavailability

Film Coating as a New Approach to Prepare Tablets Containing Long-Term Stable Lactobacillus acidophilus

This work presents a study of film coating with the vaginal strain of Lactobacillus acidophilus, the aim of which was to manufacture administrable probiotic tablets in one step and to enhance the survival rate of bacteria and their viability during storage. The results show that the film coated lactose-based tablets contained viable bacteria and the survival rate after the process was 21%, which could be enhanced up to 59% by applying protective media (trehalose, sucrose, reconstituted skim milk (RSM) during dehydration. Additionally, protective agents improved the viability of bacteria during storage too. After one year, 20% of the embedded bacteria were active when stored at –20°C, and viability dropped only one order of magnitude when stored at 7°C. It was verified that the bacteria in film coated tablets were not sensitive to higher levels of humidity owing to the moisture-moderating PVA-based coating composite

Bioimprinted lipases in PVA nanofibers as efficient immobilized biocatalysts

Immobilization of lipases from Pseudomonas fluorescens (Lipase AK), Burkholderia (Pseudomonas) cepacia (Lipase PS) and lipase B from Pseudozyma (Candida) antarctica (CaLB) was investigated by entrapment in electrospun poly(vinyl alcohol) (PVA) nanofibers. The activity and selectivity of the lipases entrapped in PVA nanofibers were characterized in kinetic resolution of racemic secondary alcohols using acylation in organic media. Potential bioimprinting effect of eight substrate mimicking additives [polyethylene glycols (PEGs), non-ionic detergents (NIDs) and various organosilanes] was tested with the fiber-entrapped lipases. The nanofibrous lipase biocatalyst entrapped in the presence of the additives were also characterized by rheology, differential scanning calorimetry and scanning electron microscopy. In addition to the known lipase-bioimprinting agents (PEGs, NIDs), phenyl- and octyltriethoxysilane also enhanced substantially the biocatalytic properties of lipases in their electrospun PVA fiber-entrapped forms. The reasons of bioimprinting effect of several additives were rationalized by docking studies in the open and closed form of CaLB

Comparison of multivariate linear regression methods in micro-Raman spectrometric quantitative characterization

Chemical imaging was used in this study as a powerful analytical tool to characterize pharmaceuticals in solid form. The majority of analyses are evaluated with bilinear modelling using only the pure component spectra or just the chemical images themselves to estimate the concentrations in each pixel, which are far from true quantitative determination. Our aim was to create more accurate concentration images using regression methods. For the first time in chemical imaging, variable selections with interval partial least squares (PLS) and with genetic algorithms (PLS-GA) were applied to increase the efficiency of the models. These were compared to numerous bilinear modelling and multivariate linear regression methods such as univariate regression, classical least squares (CLS), multivariate curve resolution-alternating least squares (MCR-ALS), principal component regression (PCR) and partial least squares (PLS). Two component spray-dried pharmaceuticals were used as a model. The paper is shown that, in contrast to the usual way of using either external validation or cross-validation, both should be performed simultaneously in order to get a clear picture of the prediction errors and to be able to select the appropriate models. Using PLS with variable selection, the root mean square errors were reduced to 3% per pixel by keeping only those peaks that are truly necessary for the estimation of concentrations. It is also shown that interval PLS can point out the best peak for univariate regression, and can thereby be of great help even when regulations allow only univariate models for product quality testing. Variable selection, besides yielding more accurate overall concentrations across a Raman map, also reduces the deviation among pixel concentrations within the images, thereby increasing the sensitivity of homogeneity studies. Copyright (c) 2015 John Wiley & Sons, Ltd

Emergency Thoracostomy as a Safe and Effective Intervention in Prehospital Trauma : A Five Year Experience from the Hungarian Air Ambulance

Traumatic tension pneumothorax is one of the most frequent causes of early mortality among the severely injured. Different methods are recommended for chest decompression. The aim of this study is to examine whether emergency thoracostomy can improve the real 30-day survival compared to the expected Revised Trauma Score (RTS) based survival, the Return of Spontaneous Circulation (ROSC) rate in Traumatic Cardiac Arrest (TCA), reduce the occurrence of tension pneumothorax (tPTX) and to determine the complication rate of the intervention