Preliminary Study on the Development of Caffeine Oral Solid Form 3D Printed by Semi-Solid Extrusion for Application in Neonates.

Apnea of prematurity can be treated with a body-weight-adjusted dosage of caffeine. Semi-solid extrusion (SSE) 3D printing represents an interesting approach to finely tailor personalized doses of active ingredients. To improve compliance and ensure the right dose in infants, drug delivery systems such as oral solid forms (orodispersible film, dispersive form, and mucoadhesive form) can be considered.

Alginate ester: New moisture-scavenging excipients for direct compressible pharmaceutical tableting.

The objective of this work is to evaluate methyl ester alginates and alginic acid (AA) as moisture-scavenging excipients for the formulation of aspirin tablets obtained by direct compression. The tablets were stored at accelerated conditions (40 °C/75 % RH) and assessed for changes in tensile strength, mass, thickness and disintegration time. While moisture caused a reduction in the hardness of MCC and AA tablets, hardness of the tablets made from methylated materials was virtually unaffected.

Chemoprevention with a tea from hawthorn () leaves and flowers attenuates colitis in rats by reducing inflammation and oxidative stress.

The purpose of the study was to determine the effects of a tea from the leaves and flowers of in rats with colitis. Colitis was induced by administration of 2,4,6-trinitrobenzene sulfonic acid. Hawthorn tea (HT) (100 mg/kg) was given via gavage for 21 days and the mesalamine drug (100 mg/kg) was administrated during the period of disease onset.

A QbD Approach for Evaluating the Effect of Selective Laser Sintering Parameters on Printability and Properties of Solid Oral Forms.

The aim of this work was to investigate the effect of process parameters on the printability of a formulation containing copovidone and paracetamol, and on the properties of solid oral forms 3D-printed through selective laser sintering. Firstly, the influence of the heating temperature was evaluated individually, and it was revealed that this parameter was critical for printability, as a sufficiently high temperature (100 °C) is necessary to avoid curling. Secondly, the effects of laser power, scan speed, and layer thickness were determined using a Box-Behnken design.

Investigating the Potential Plasticizing Effect of Di-Carboxylic Acids for the Manufacturing of Solid Oral Forms with Copovidone and Ibuprofen by Selective Laser Sintering.

In selective laser sintering (SLS), the heating temperature is a critical parameter for printability but can also be deleterious for the stability of active ingredients. This work aims to explore the plasticizing effect of di-carboxylic acids on reducing the optimal heating temperature (OHT) of polymer powder during SLS. First, mixtures of copovidone and di-carboxylic acids (succinic, fumaric, maleic, malic and tartaric acids) as well as formulations with two forms of ibuprofen (acid and sodium salt) were prepared to sinter solid oral forms (SOFs), and their respective OHT was determined.

Selective Laser Sintering of Solid Oral Dosage Forms with Copovidone and Paracetamol Using a CO Laser.

Material suitability needs to be considered for the 3D printing of solid oral dosage forms (SODFs). This work aims to assess the suitability of a CO laser (λ = 10.6 μm) for selective laser sintering of SODFs containing copovidone and paracetamol.

Screening for pancreatic lipase natural modulators by capillary electrophoresis hyphenated to spectrophotometric and conductometric dual detection.

The search for novel pancreatic lipase (PL) inhibitors has gained increasing attention in recent years. For the first time, a dual detection capillary electrophoresis (CE)-based homogeneous lipase assay was developed employing both the offline and online reaction modes. The hydrolysis of 4-nitrophenyl butyrate (4-NPB) catalyzed by PL into 4-nitrophenol and butyrate was monitored by spectrophotometric and conductimetric detection, respectively.

Water-Based Extraction of Bioactive Principles from Blackcurrant Leaves and : A Comparative Study.

The water-based extraction of bioactive components from flavonoid-rich medicinal plants is a key step that should be better investigated. This is especially true when dealing with easy-to-use home-made conditions of extractions, which are known to be a bottleneck in the course for a better control and optimization of the daily uptake of active components from medicinal plants. In this work, the water-based extraction of Blackcurrant () leaves (BC) and (CA) known to have complementary pharmacological properties, was studied and compared with a previous work performed on the extraction of Hawthorn ( HAW).

Optimizing Water-Based Extraction of Bioactive Principles of Hawthorn: From Experimental Laboratory Research to Homemade Preparations.

Hawthorn (Crataegus) is used for its cardiotonic, hypotensive, vasodilative, sedative, antiatherosclerotic, and antihyperlipidemic properties. One of the main goals of this work was to find a well-defined optimized extraction protocol usable by each of us that would lead to repeatable, controlled, and quantified daily uptake of active components from hawthorn at a drinkable temperature (below 60 °C). A thorough investigation of the extraction mode in water (infusion, maceration, percolation, ultrasounds, microwaves) on the yield of extraction and the amount of phenolic compounds, flavonoids, and proanthocyanidin oligomers as well as on the Ultra High Performance Liquid Chromatography (UHPLC) profiles of the extracted compounds was carried out.

How Prebiotic Chemistry and Early Life Chose Phosphate.

The very specific thermodynamic instability and kinetic stability of phosphate esters and anhydrides impart them invaluable properties in living organisms in which highly efficient enzyme catalysts compensate for their low intrinsic reactivity. Considering their role in protein biosynthesis, these properties raise a paradox about early stages: How could these species be selected in the absence of enzymes? This review is aimed at demonstrating that considering mixed anhydrides or other species more reactive than esters and anhydrides can help in solving the paradox. The consequences of this approach for chemical evolution and early stages of life are analysed.

The Chemical Likelihood of Ribonucleotide-α-Amino acid Copolymers as Players for Early Stages of Evolution.

How ribosomal translation could have evolved remains an open question in most available scenarios for the early developments of life. Rather than considering RNA and peptides as two independent systems, this work is aimed at assessing the possibility of formation and stability of co-polymers or co-oligomers of α-amino acids and nucleotides from which translation might have evolved. Here we show that the linkages required to build such mixed structures have lifetimes of several weeks to months at neutral pH and 20 °C owing to the mutual protecting effect of both neighboring phosphoramidate and ester functional groups increasing their stability by factors of about 1 and 3 orders of magnitude, respectively.

Field evaluation of a real time loop-mediated isothermal amplification assay (RealAmp) for malaria diagnosis in Cruzeiro do Sul, Acre, Brazil.

Conventional molecular methods, such as nested polymerase chain reaction (PCR), are very sensitive for detection of malaria parasites, but require advanced laboratory equipment and trained personnel. Real-time loop-mediated isothermal amplification (RealAmp), a loop-mediated isothermal amplification-based molecular tool (LAMP), facilitates rapid target amplification at a single temperature setting, reducing the need for sophisticated equipment. We evaluated the performance of a field-adapted RealAmp assay for malaria diagnosis in Cruzeiro do Sul, Acre State, Brazil, a remote area in Brazil with limited laboratory capabilities.

Diastereoselective Synthesis of a Dyn[3]arene with Distinct Binding Behaviors toward Linear Biogenic Polyamines.

The extension of the family of dyn[ n]arenes toward a three-membered macrocycle is reported. Through a templated approach, a single diastereoisomer of a dyn[3]arene that bears six carboxyl groups could be isolated by precipitation in 59-63% yield and excellent purity (≥95%). A combination of experimental and computational experiments in water at physiological pH revealed that the macrocycle could bind parent biogenic polyamines with a unique diversity of surface-binding modes.

Effect of Dendrigraft Generation on the Interaction between Anionic Polyelectrolytes and Dendrigraft Poly(l-Lysine).

In this present work, three generations of dendrigraft poly(l-Lysine) (DGL) were studied regarding their ability to interact with linear poly (acrylamide--2-acrylamido-2-methyl-1-propanesulfonate) (PAMAMPS) of different chemical charge densities (30% and 100%). Frontal analysis continuous capillary electrophoresis (FACCE) was successfully applied to determine binding constants and binding stoichiometries. The effect of DGL generation on the interaction was evaluated for the first three generations (G2, G3, and G4) at different ionic strengths, and the effect of ligand topology (linear PLL vs.

Size characterization of lipid-based self-emulsifying pharmaceutical excipients during lipolysis using Taylor dispersion analysis with fluorescence detection.

Self-emulsifying drug delivery systems based on lipids have gained in interest in recent years due to their capacity to enhance the bioavailability of poorly water soluble drugs. Their oral intake suggests that they will be in contact with gastric and pancreatic enzymes during their passage through the gastrointestinal tract. The study of the evolution of such systems in the presence of enzymes is thus essential to develop better drug delivery vehicles.

Digitizing Poly-l-lysine Dendrigrafts: From Experimental Data to Molecular Dynamics Simulations.

Despite the growing use of poly-l-lysine dendrigrafts in biomedical applications, a deeper understanding of the molecular level properties of these macromolecules is missing. Herein, we report a simple methodology for the construction of three-dimensional structures of poly-l-lysine dendrigrafts and the subsequent investigation of their structural features using microsecond molecular dynamics simulations. This methodology relies on the encoding of the polymers' experimental characterizations (i.

The Prebiotic C-Terminal Elongation of Peptides Can Be Initiated by N-Carbamoyl Amino Acids.

The formation of peptides upon 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC)-promoted activation of N-carbamoylamino acids (CAA), was considered in the scope of our recent works on carbodiimide promoted C-terminus elongation of peptides in a prebiotic context. Thus EDC promoted activation of CAA derivatives of Tyr(Me) or Ala in dilute aqueous medium pH 5.5-6.

Mixed Anhydride Intermediates in the Reaction of 5(4H)-Oxazolones with Phosphate Esters and Nucleotides.

5(4H)-Oxazolones can be formed through the activation of acylated α-amino acids or of peptide C termini. They constitute potentially activated intermediates in the abiotic chemistry of peptides that preceded the origin of life or early stages of biology and are capable of yielding mixed carboxylic-phosphoric anhydrides upon reaction with phosphate esters and nucleotides. Here, we present the results of a study aimed at investigating the chemistry that can be built through this interaction.

Factors associated with the occurrence of Triatoma sordida (Hemiptera: Reduviidae) in rural localities of Central-West Brazil.

This study estimates the factors of artificial environments (houses and peridomestic areas) associated with Triatoma sordida occurrence. Manual searches for triatomines were performed in 136 domiciliary units (DUs) in two rural localities of Central-West Brazil. For each DU, 32 structural, 23 biotic and 28 management variables were obtained.

Evolutionary importance of the intramolecular pathways of hydrolysis of phosphate ester mixed anhydrides with amino acids and peptides.

Aminoacyl adenylates (aa-AMPs) constitute essential intermediates of protein biosynthesis. Their polymerization in aqueous solution has often been claimed as a potential route to abiotic peptides in spite of a highly efficient CO2-promoted pathway of hydrolysis. Here we investigate the efficiency and relevance of this frequently overlooked pathway from model amino acid phosphate mixed anhydrides including aa-AMPs.

Multi-technique characterization of poly-L-lysine dendrigrafts-Cu(II) complexes for biocatalysis.

Poly-L-lysine is a biocompatible polymer used for drug or gene delivery, for transport through cellular membranes, and as nanosized magnetic resonance imaging contrast agents. Cu(II)-poly-L-lysine complexes are of particular interest for their role in biocatalysis. In this study, poly-L-lysine dendrigrafts (DGLs) at different generations (G2, G3, and G4) are synthesized and characterized in absence and presence of Cu(II) by means of electron paramagnetic resonance (EPR), UV-Vis, potentiometric titration and circular dichroism (CD).

Diastereoselectivity in prebiotically relevant 5(4H)-oxazolone-mediated peptide couplings.

A stereochemical study of a potentially prebiotic peptide-forming reaction was carried out as the first part of a systems chemistry investigation of potential paths for symmetry breaking. Substantial diastereomeric excesses result from a fast epimerization of the 5(4H)-oxazolone intermediate in aqueous solution.

Isoprostanes and phytoprostanes: Bioactive lipids.

Polyunsaturated fatty acids (PUFA) are important constituents in all eukaryotic organisms, contributing to the structural integrity of biological membranes and serving as precursors for enzymatically-generated local hormones. In addition to these functions, PUFA can generate by a free radical-initiated mechanism, key products which participate in a variety of pathophysiological processes. In particular, free radical-catalyzed peroxidation of PUFA leads to in vivo formation of isoprostanes (IsoP), neuroprostanes (NeuroP), and phytoprostanes (PhytoP) which display a wide range of biological actions.

[Anophelines of Santa Catarina (Diptera: culicidae), Brazil].

Introduction: The Amazon region of Brazil is endemic for malaria. In the State of Santa Catarina, malaria was eliminated in the 1980s. Since then, a few sporadic isolated autochthonous cases have occurred.