Convolutional neural networks for segmentation of FIB-SEM nanotomography data from porous polymer films for controlled drug release.

Phase-separated polymer films are commonly used as coatings around pharmaceutical oral dosage forms (tablets or pellets) to facilitate controlled drug release. A typical choice is to use ethyl cellulose and hydroxypropyl cellulose (EC/HPC) polymer blends. When an EC/HPC film is in contact with water, the leaching out of the water-soluble HPC phase produces an EC film with a porous network through which the drug is transported.

Quantification of surface composition and surface structure of inhalation powders using TOF-SIMS.

A multivariate TOF-SIMS methodology has been developed and applied to quantify surface composition and chemical distribution for dry powder blends. Surface properties are often critical to the behavior of powder formulations, especially in the case of dry powders for inhalation, as surface properties directly affect inter-particulate forces and, hence, the dispersibility of the formulation. The mass spectrum at each pixel was fit to a linear combination of reference spectra obtained by non-negatively constrained alternating least squares.

Characterization of acoustic emission analysis in applications for inhalation device performance assessment.

Acoustic Emission (AE) measurement technology has gained wide appreciation in material sciences and process monitoring. In inhalation research, AE has been used for adherence indicating applications in clinical studies. Promising results from feasibility studies using AE combined with multivariate data analysis (AE-MVDA) in the analysis of devices for inhalation have prompted a broader study reported in this paper.

New features of arabinoxylan ethers revealed by using multivariate analysis.

Hemicelluloses are a relatively unused renewable resource. One reason is their broad structure variety that makes it hard to understand structure-property relations. In this study arbinoxylan, extracted from barley husk, was chemically modified into hydroxypropyl methyl-, hydroxypropyl- and methyl arabinoxylan.

Imaging and Identification of Marine Algal Bioactive Compounds by Surface Enhanced Raman Spectroscopy (SERS).

Surface-enhanced Raman spectroscopy (SERS) is a highly selective technique that can be used for imaging of single algae cells. In contrast to normal Raman spectroscopy, SERS utilizes light interaction with colloidal gold or silver particles working as antennas to match the sensitivity of fluorescence measurements. Furthermore, SERS enables a more profound picture of not only the analyte of interest but also the present biological matrix without the need for additional fluorescence labelling.

Roll compaction process modeling: transfer between equipment and impact of process parameters.

In this study, the roll compaction of an intermediate drug load formulation was performed using horizontally and vertically force fed roll compactors. The horizontally fed roll compactor was equipped with an instrumented roll technology allowing the direct measurement of normal stress at the roll surface, while the vertically fed roll compactor was equipped with a force gauge between the roll axes. Furthermore, characterization of ribbons, granules and tablets was also performed.

Near-infrared chemical imaging (NIR-CI) on roll compacted ribbons and tablets--multivariate mapping of physical and chemical properties.

Near-infrared chemical imaging (NIR-CI) is an attractive technique within the pharmaceutical industry, where tools are continuously in demand to assess the quality of the intermediate and final products. The present paper demonstrates how NIR-CI in combination with multivariate methods was utilized to spatially map physical properties and content of roll compacted ribbons and tablets. Additionally, extracted textural parameters from tablet images were correlated to the design parameters of the roll compaction process as well as to the physical properties of the granules.

Comparison of exhaled endogenous particles from smokers and non-smokers using multivariate analysis.

Background: Smoking, along with many respiratory diseases, has been shown to induce airway inflammation and alter the composition of the respiratory tract lining fluid (RTLF). We have previously shown that the phospholipid and protein composition of particles in exhaled air (PEx) reflects that of RTLF. In this study, we hypothesized that the composition of PEx differs between smokers and non-smokers, reflecting inflammation in the airways.

A quality by design approach to investigate the effect of mannitol and dicalcium phosphate qualities on roll compaction.

Roll compaction is a continuous process for solid dosage form manufacturing increasingly popular within pharmaceutical industry. Although roll compaction has become an established technique for dry granulation, the influence of material properties is still not fully understood. In this study, a quality by design (QbD) approach was utilized, not only to understand the influence of different qualities of mannitol and dicalcium phosphate (DCP), but also to predict critical quality attributes of the drug product based solely on the material properties of that filler.

Chemical images of marine bio-active compounds by surface enhanced Raman spectroscopy and transposed orthogonal partial least squares (T-OPLS).

Surface enhanced Raman spectroscopy combined with transposed Orthogonal Partial Least Squares (T-OPLS) was shown to produce chemical images of the natural antibacterial surface-active compound 1,1,3,3-tetrabromo-2-heptanone (TBH) on Bonnemaisonia hamifera. The use of gold colloids functionalised with the internal standard 4-mercapto-benzonitrile (MBN) made it possible to create images of the relative concentration of TBH over the surfaces. A gradient of TBH could be mapped over and in the close vicinity of the B.

TOF-SIMS analysis of exhaled particles from patients with asthma and healthy controls.

Particles in exhaled air (PEx) may reflect the composition of respiratory tract lining fluid (RTLF); thus, there is a need to assess their potential as sources of biomarkers for respiratory diseases. In the present study, we compared PEx from patients with asthma and controls using time-of-flight-secondary ion mass spectrometry (TOF-SIMS) and multivariate analysis. Particles were collected using an instrument developed in-house.

Combining experimental design and orthogonal projections to latent structures to study the influence of microcrystalline cellulose properties on roll compaction.

Roll compaction is gaining importance in pharmaceutical industry for the dry granulation of heat or moisture sensitive powder blends with poor flowing properties prior to tabletting. We studied the influence of microcrystalline cellulose (MCC) properties on the roll compaction process and the consecutive steps in tablet manufacturing. Four dissimilar MCC grades, selected by subjecting their physical characteristics to principal components analysis, and three speed ratios, i.

Multivariate analysis of the relation between immune dysfunction and treatment intensity in children with acute lymphoblastic leukemia.

Background: Immunoreconstitution following childhood acute lymphoblastic leukemia (ALL) is a complex process during which various immune functions recover differentially. This process is difficult to elucidate since variables are interrelated and require simultaneous evaluation, rendering conventional statistical methods inappropriate.

Procedure: We used principal components analysis (PCA) and projection of latent structures (PLS) to evaluate immune competence in 32 children treated for ALL.

Transfer of NIR calibrations for pharmaceutical formulations between different instruments.

In order to evaluate how well existing techniques for transferring NIR calibrations perform for solid pharmaceutical formulations, a study on four assays of active ingredients was undertaken. The study included two configurations of dispersive NIR instruments and one Fourier transform (FT) instrument. Three methods for calibration transfer: slope/bias correction, local centring and piecewise direct standardisation (PDS), were tested and evaluated.

Evaluation of basic algorithms for transferring quantitative multivariate calibrations between scanning grating and FT NIR spectrometers.

A key issue in near infrared spectroscopy (NIR) is the possibility to use calibrations generated on one instrument for predictions on others. A number of methods for calibration transfer have been proposed, but which method to choose is typically not straightforward. An evaluation of a number of methods for transferring quantitative calibrations between different instruments was carried out on near infrared diffuse-reflectance data from a pharmaceutical formulation.

Surface-enhanced Raman scattering imaging of single living lymphocytes with multivariate evaluation.

This paper is aimed to show the possibility to determine individual organic compounds introduced into single living cells with surface-enhanced Raman spectroscopy (SERS). Surface enhancement was achieved with gold colloids that were allowed to diffuse into lymphocytes. An introduced analyte, rhodamine 6G, could be imaged together with for example nucleotides and amino acids of the cell.

Internal standard in surface-enhanced Raman spectroscopy.

A method is presented for the use of SAM layers as internal standards for calibration in surface-enhanced Raman spectroscopy. Three cyano-containing compounds were attached to gold colloids via a metal-sulfur bond and evaluated for spectral stability and normalization capacity. The results show that the analyte, rhodamine 6G, and the internal standard signal enhancement covaried, and it was possible to quantify the analyte with PLS.

Multivariate evaluation of doxorubicin surface-enhanced Raman spectra.

Multivariate evaluation of surface-enhanced Raman spectra of doxorubicin in plasma was performed. In a principal component analysis (PCA) all spectral features were modelled into three principal components. The major variation of the data was shown to be the variation of doxorubicin Raman signal together with the doxorubicin fluorescence, whereas the variation due to plasma was of minor importance.

The synthesis of metoprolol monitored using Raman spectroscopy and chemometrics.

The synthesis of Metoprolol base was studied using Raman spectroscopy with a 785-nm laser, optical fibres, a holographic transmission grating, confocal optics and a charge-coupled device (CCD) detector. The reaction mixture was heated according to a temperature gradient and spectra of the reaction mixture were obtained by focusing the laser beam through ordinary reaction flasks. Because of overlapping bands, multivariate techniques such as principal components analysis (PCA) and partial least-squares projections to latent structures (PLS) were used in the evaluation of the obtained spectra.

Quantitative analysis of film coating in a fluidized bed process by in-line NIR spectrometry and multivariate batch calibration.

A method is described which enables real-time analysis of film coating on pharmaceutical pellets during an industrial manufacturing process. Measurements were conducted on the solid particulate material by near-infrared (NIR) spectrometry utilizing a diffuse reflectance fiber-optic probe positioned inside a fluidized bed process vessel. Time series of NIR spectra from 11 batches generated a three-way data matrix that was unfolded and modeled by partial least squares (PLS) in a multivariate batch calibration.

Monitoring of a film coating process for tablets using near infrared reflectance spectrometry.

A process analytical chemical method using near infrared diffuse reflectance spectrometry was developed for the determination of the amount of tablet coating on single tablets. This method is based on calibration of the spectra versus the added mass of coating solution. The tablet core was composed of two halves of different chemical composition and spectra were recorded from both sides of the tablets.

Vibrational spectrometry for the assessment of active substance in metoprolol tablets: a comparison between transmission and diffuse reflectance near-infrared spectrometry.

Near-infrared spectrometry (NIR) was used to quantify metroprolol succinate in controlled release tablets. Metoprolol tablets were made according to an experimental design using different strengths around a central strength of 47.5 mg per tablet.

Multicomponent analysis: a case report.

Three cases are described. Case 1: kinetic studies often need high time resolution measurements in order to follow the pattern of reactions taking place during the experiment. This is often laborious to achieve with the collection of fractions for chromatographic separation.