Optimization of silver nanoparticles synthesis by chemical reduction to enhance SERS quantitative performances: Early characterization using the quality by design approach.

Surface-enhanced Raman scattering (SERS) is a vibrational widely used technique thanks to its multiple advantages such as its high specificity and sensitivity. The Raman signal exaltation comes from the use of metallic nanoparticles (Nps) acting as antennas by amplifying the Raman scattering. Controlling the Nps synthesis is a major point for the implementation of SERS in routine analysis and especially in quantitative applications.

Application of design space and quality by design methodologies combined with ultra high-performance liquid chromatography for the optimization of the sample preparation of complex pharmaceutical dosage forms.

Accurate and precise analytical measurements play a significant role in assessments and decisions that are made throughout the drug development process. Developing a robust and reliable sample preparation is essential for drug product formulations to generate consistent results guaranteeing the product quality. However, due to the complex nature of the different pharmaceutical formulations with diverse excipients, developing robust sample preparation methods can be challenging and time consuming.

Optimizing the soft independent modeling of class analogy (SIMCA) using statistical prediction regions.

The ultimate goal of a one-class classifier like the "rigorous" soft independent modeling of class analogy (SIMCA) is to predict with a certain confidence probability, the conformity of future objects with a given reference class. However, the SIMCA model, as currently implemented often suffers from an undercoverage problem, meaning that its observed sensitivity often falls far below the desired theoretical confidence probability, hence undermining its intended use as a predictive tool. To overcome the issue, the most reported strategy in the literature, involves incrementing the nominal confidence probability until the desired sensitivity is obtained in cross-validation.

Potato Production in Northwestern Europe (Germany, France, the Netherlands, United Kingdom, Belgium): Characteristics, Issues, Challenges and Opportunities.

In Northwestern Europe, Germany, France, the Netherlands, the UK and Belgium constitute the biggest five potato producers, with total potato crop production around 60% of EU-28 production before Brexit. Soil and climate conditions are highly favourable for potato growth in this region. Production is under driving forces of (i) the potato processing industry, particularly in Belgium; (ii) the innovation for fresh potato in the UK, France and Germany; (iii) the leadership of Germany and the Netherlands for starch potato; and (iv) the dominance of the Netherlands for seed production.

A probabilistic class-modelling method based on prediction bands for functional spectral data: Methodological approach and application to near-infrared spectroscopy.

Class-modelling methods aim to predict the conformity of new unknown samples with a single target class, using statistical decision rules built exclusively with objects of that class. This article introduces a novel class-modelling method for spectral data. The method uses the concept of β%-prediction band for functional data to classify spectra.

Controlling the Reproducibility of AC50 Estimation during Compound Profiling through Bayesian β-Expectation Tolerance Intervals.

During drug discovery, compounds/biologics are screened against biological targets of interest to find drug candidates with the most desirable activity profile. The compounds are tested at multiple concentrations to understand the dose-response relationship, often summarized as AC50 values and used directly in ranking compounds. Differences between compound repeats are inevitable because of experimental noise and/or systematic error; however, it is often desired to detect the latter when it occurs.

Interaction between the scaffold proteins CBP by IQGAP1 provides an interface between gene expression and cytoskeletal activity.

Crosstalk between cellular pathways is often mediated through scaffold proteins that function as platforms for the assembly of signaling complexes. Based on yeast two-hybrid analysis, we report here the interaction between two complex scaffold proteins, CREB-binding protein (CBP) and the Ras GTPase-activating-like protein 1 (IQGAP1). Dissection of the interaction between the two proteins reveals that the central, thus far uncharacterized, region of IQGAP1 interacts with the HAT domain and the C-terminal intrinsically disordered region of CBP (termed ID5).

Quantification of Intrinsically Disordered Proteins: A Problem Not Fully Appreciated.

Protein quantification is essential in a great variety of biochemical assays, yet the inherent systematic errors associated with the concentration determination of intrinsically disordered proteins (IDPs) using classical methods are hardly appreciated. Routinely used assays for protein quantification, such as the Bradford assay or ultraviolet absorbance at 280 nm, usually seriously misestimate the concentrations of IDPs due to their distinct and variable amino acid composition. Therefore, dependable method(s) have to be worked out/adopted for this task.

Implementation of a generic SFC-MS method for the quality control of potentially counterfeited medicinal cannabis with synthetic cannabinoids.

In this study, we describe the development of a SFC-MS method for the quality control of cannabis plants that could be potentially adulterated with synthetic cannabinoids. Considering the high number of already available synthetic cannabinoids and the high rate of development of novel structures, we aimed to develop a generic method suitable for the analysis of a large panel of substances using seventeen synthetic cannabinoids from multiple classes as model compounds. Firstly, a suitable column was chosen after a screening phase.

"NOTA-PRGD and NODAGA-PRGD : Bioconjugation, characterization, radiolabelling, and design space".

This work reports on the development of amide bond bioconjugation for the production of -NOTA and -NODAGA PRGD using batch strategy and microfluidic reactor technology. The final radiolabelling step was fully optimized using Design of Experiments and Design Space approaches, hence targeting robust labelling yields in routine. Optimal labelling conditions were defined in sodium acetate buffer as 168 μg/mL peptide concentration, 4.

Linking functions: an additional role for an intrinsically disordered linker domain in the transcriptional coactivator CBP.

The multi-domain transcriptional coactivators CBP/p300 integrate a multitude of signaling inputs, interacting with more than 400 proteins via one or more of their globular domains. While CBP/p300 function is typically considered in terms of these structured domains, about half of the protein consists of intrinsically disordered regions (IDRs) of varying length. However, these IDRs have only been thought of as linkers that allow flexible spatial arrangement of the structured domains, but recent studies have shown that similar IDRs mediate specific and critical interactions in other proteins.

To be disordered or not to be disordered: is that still a question for proteins in the cell?

There is ample evidence that many proteins or regions of proteins lack a well-defined folded structure under native-like conditions. These are called intrinsically disordered proteins (IDPs) or intrinsically disordered regions (IDRs). Whether this intrinsic disorder is also their main structural characteristic in living cells has been a matter of intense debate.

Application of design space optimization strategy to the development of LC methods for simultaneous analysis of 18 antiretroviral medicines and 4 major excipients used in various pharmaceutical formulations.

As one of the world's most significant public health challenges in low- and middle-income countries, HIV/AIDS deserves to be treated with appropriate medicines, however which are not spared from counterfeiting. For that, we developed screening and specific HPLC methods that can analyze 18 antiretroviral medicines (ARV) and 4 major excipients. Design of experiments and design space methodology were initially applied for 15 ARV and the 4 excipients with prediction thanks to Monte Carlo simulations and focusing on rapidity and affordability thus using short column and low cost organic solvent (methanol) in gradient mode with 10mM buffer solutions of ammonium hydrogen carbonate.

Quantitative determination of salbutamol sulfate impurities using achiral supercritical fluid chromatography.

In the last years, supercritical fluid chromatography has largely been acknowledged as a singular and performing technique in the field of separation sciences. Recent studies highlighted the interest of SFC for the quality control of pharmaceuticals, especially in the case of the determination of the active pharmaceutical ingredient (API). Nevertheless, quality control requires also the determination of impurities.

Continuous production of itraconazole-based solid dispersions by hot melt extrusion: Preformulation, optimization and design space determination.

The purpose of this work was to increase the solubility and the dissolution rate of itraconazole, which was chosen as the model drug, by obtaining an amorphous solid dispersion by hot melt extrusion. Therefore, an initial preformulation study was conducted using differential scanning calorimetry, thermogravimetric analysis and Hansen's solubility parameters in order to find polymers which would have the ability to form amorphous solid dispersions with itraconazole. Afterwards, the four polymers namely Kollidon VA64, Kollidon 12PF, Affinisol HPMC and Soluplus, that met the set criteria were used in hot melt extrusion along with 25wt.

Screening study of SFC critical method parameters for the determination of pharmaceutical compounds.

Nowadays, supercritical fluid chromatography is commonly presented as a promising alternative technique in the field of separation sciences. Nevertheless the selection of chromatographic conditions and sample preparation of pharmaceutical compounds remain a challenge and peak distortion was previously highlighted. The main objective of the present work was to evaluate the impact of different critical method parameters (CMPs), i.

Optimization of a PGSS (particles from gas saturated solutions) process for a fenofibrate lipid-based solid dispersion formulation.

The aim of this study was to develop a formulation containing fenofibrate and Gelucire(®) 50/13 (Gattefossé, France) in order to improve the oral bioavailability of the drug. Particles from gas saturated solutions (PGSS) process was chosen for investigation as a manufacturing process for producing a solid dispersion. The PGSS process was optimized according to the in vitro drug dissolution profile obtained using a biphasic dissolution test.

Optimization of a pharmaceutical tablet formulation based on a design space approach and using vibrational spectroscopy as PAT tool.

The aim of the present study was to optimize a tablet formulation using a quality by design approach. The selected methodology was based on the variation of the filler grade, taking into account the particle size distribution (PSD) of active pharmaceutical ingredient (API) in order to improve five critical quality attributes (CQAs). Thus, a mixture design of experiments (DoE) was performed at pilot scale.

A quality by design approach for longitudinal quality attributes.

The concept of quality by design (QbD) as published in ICH-Q8 is currently one of the most recurrent topics in the pharmaceutical literature. This guideline recommends the use of information and prior knowledge gathered during pharmaceutical development studies to provide a scientific rationale for the manufacturing process of a product and provide guarantee of future quality. This poses several challenges from a statistical standpoint and requires a shift in paradigm from traditional statistical practices.

Analytical procedure validation and the quality by design paradigm.

Since the adoption of the ICH Q8 document concerning the development of pharmaceutical processes following a quality by design (QbD) approach, there have been many discussions on the opportunity for analytical procedure developments to follow a similar approach. While development and optimization of analytical procedure following QbD principles have been largely discussed and described, the place of analytical procedure validation in this framework has not been clarified. This article aims at showing that analytical procedure validation is fully integrated into the QbD paradigm and is an essential step in developing analytical procedures that are effectively fit for purpose.

Mechanistic insights in glycation-induced protein aggregation.

Protein glycation causes loss-of-function through a process that has been associated with several diabetic-related diseases. Additionally, glycation has been hypothesized as a promoter of protein aggregation, which could explain the observed link between hyperglycaemia and the development of several aggregating diseases. Despite its relevance in a range of diseases, the mechanism through which glycation induces aggregation remains unknown.

A new criterion to assess distributional homogeneity in hyperspectral images of solid pharmaceutical dosage forms.

During galenic formulation development, homogeneity of distribution is a critical parameter to check since it may influence activity and safety of the drug. Raman hyperspectral imaging is a technique of choice for assessing the distributional homogeneity of compounds of interest. Indeed, the combination of both spectroscopic and spatial information provides a detailed knowledge of chemical composition and component distribution.

Evaluation of the quantitative performances of supercritical fluid chromatography: from method development to validation.

Recently, the number of papers about SFC increased drastically but scientists did not truly focus their work on quantitative performances of this technique. In order to prove the potential of UHPSFC, the present work discussed about the different steps of the analytical life cycle of a method: from development to validation and application. Moreover, the UHPSFC quantitative performances were evaluated in comparison with UHPLC, which is the main technique used for quality control in the pharmaceutical industry and then could be considered as a reference.

Robust method optimization strategy-a useful tool for method transfer: the case of SFC.

The concept of Quality by Design (QbD) is now well established in pharmaceutical industry and should be applied to the development of any analytical methods. In this context, the key concept of Design Space (DS) was introduced in the field of analytical method optimization. In chromatographic words, the DS is the space of chromatographic conditions that will ensure the quality of peaks separation, thus DS is a zone of robustness.

pE-DB: a database of structural ensembles of intrinsically disordered and of unfolded proteins.

The goal of pE-DB (http://pedb.vib.be) is to serve as an openly accessible database for the deposition of structural ensembles of intrinsically disordered proteins (IDPs) and of denatured proteins based on nuclear magnetic resonance spectroscopy, small-angle X-ray scattering and other data measured in solution.