Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Multidrug Cocrystal of Anticonvulsants: Influence of Strong Intermolecular Interactions on Physiochemical Properties.

ABSTRACT: A drug-drug cocrystal of two anticonvulsants, lamotrigine and phenobarbital, is presented. In the crystal structure, molecules form heterodimers via N-H···O and N-H···N hydrogen bonding. The intrinsic dissolution rate (IDR) and solubility of the cocrystal were measured in phosphate buffer (pH 7.2) and simulated gastric fluid (without pepsin), and compared to pure APIs. Dissolution experiments found suppressed IDR of the cocrystal with rates in the order pure PB > pure LTG > cocrystal. The solubility measurements were consistent with the dissolution behavior. The presence of strong heterodimers in the cocrystal compared to weaker homodimers in the parent drugs is implicated for the reduced solubility and dissolution rate.

SUBMITTER: Kaur R

PROVIDER: S-EPMC6752747 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Multidrug Cocrystal of Anticonvulsants: Influence of Strong Intermolecular Interactions on Physiochemical Properties.

Kaur Ramanpreet R Cavanagh Katie L KL Rodríguez-Hornedo Naír N Matzger Adam J AJ

Crystal growth & design 20170908 10

A drug-drug cocrystal of two anticonvulsants, lamotrigine and phenobarbital, is presented. In the crystal structure, molecules form heterodimers via N-H···O and N-H···N hydrogen bonding. The intrinsic dissolution rate (IDR) and solubility of the cocrystal were measured in phosphate buffer (pH 7.2) and simulated gastric fluid (without pepsin), and compared to pure APIs. Dissolution experiments found suppressed IDR of the cocrystal with rates in the order pure PB > pure LTG > cocrystal. The solubi ...[more]

PMID: 31537980

Similar Datasets

Influence of physiochemical properties on the subcutaneous absorption and bioavailability of monoclonal antibodies.

Project description:Many therapeutic monoclonal antibodies (mAbs) were initially developed for intravenous (IV) administration. As a means to improve mAb drug-ability and the patient experience, subcutaneous (SC) administration is an increasingly important delivery route for mAbs. Unlike IV administration, bioavailability limitations for antibodies have been reported following SC injection and can dictate whether a mAb is administered via this parenteral route. The SC bioavailability of antibodies has been difficult to predict, and it can be variable and partial, with values ranging from ~50% to 100%. The mechanisms leading to the incomplete bioavailability of some mAbs relative to others are not well understood. There are some limited data that suggest the physiochemical properties inherent to a mAb can contribute to its SC absorption, bioavailability, and in vivo fate. In this study, we evaluated the integrated influence of multiple mAb physiochemical factors on the SC absorption and bioavailability of six humanized mAbs in both rats and cynomolgus monkeys. We demonstrate the physiochemical properties of mAbs are critical to their rate and extent of SC absorption. The combination of high positive charge and hydrophobic interaction significantly reduced the rate of the evaluated mAb's SC absorption and bioavailability. Reduction or balancing of both these attributes via re-engineering the mAbs restored desirable properties of the molecules assessed. This included reduced association with SC tissue, improvements in mAb absorption from the SC space and overall SC bioavailability. Our findings point to the importance of evaluating the relative balance between various physiochemical factors, including charge, hydrophobicity, and stability, to improve the SC drug-ability of mAbs for selecting or engineering mAbs with enhanced in vivo absorption and bioavailability following SC administration.

| S-EPMC7531508 | biostudies-literature

Physiochemical Properties of Biochar and Activated Carbon from Biomass Residue: Influence of Process Conditions to Adsorbent Properties.

Project description:This study evaluates the influence of hydrothermal carbonization (HTC) or slow pyrolysis (SP) process conditions on the physicochemical properties of precursor biochars and activated carbon (AC). The AC is achieved through a direct or a two-step method with subsequent chemical activation using KOH. A theory is developed on the biochar propensity to be chemically activated based on the lignocellulosic structure composition. X-ray photoelectron spectroscopy elemental analysis shows that the O/C ratio decreases after chemical activation for HTC biochar but remains the same for SP biochar. X-ray powder diffraction indicates that the SP biochar and all ACs have broad amorphous carbon peaks, whereas corn stover and the HTC biochar have distinct cellulosic crystalline peaks. Vanillin adsorbent experiments were performed on various ACs with up to 98% reduction shown. The best adsorbent for vanillin was the AC produced directly from corn stover, followed by AC HTC and then AC SP.

| S-EPMC8153675 | biostudies-literature

Exploring the Influence of Intermolecular Interactions in Prebiotic Chemistry Using Laser Spectroscopy and Calculations.

Project description:One of the most fascinating questions in chemistry is why nature chose CGAT as the alphabet of life. Very likely, such selection was the result of multiple factors and a long period of refinement. Here, we explore how the intermolecular interactions influenced such process, by characterizing the formation of dimers between adenine, theobromine and 4-aminopyrimidine. Using a combination of mass-resolved excitation spectroscopy and DFT calculations, we determined the structure of adenine-theobromine and 4-aminopyrimidine-theobromine dimers. The binding energy of these dimers is very close to the canonical adenine-thymine nucleobases. Likewise, the dimers are able to adopt Watson-Crick conformations. These findings seem to indicate that there were many options available to build the first versions of the informational polymers, which also had to compete with other molecules, such as 4-aminopyrimidine, which does not have a valid attaching point for a saccharide. For some reason, nature did not select the most strongly-bonded partners or if it did, such proto-bases were later replaced by the nowadays canonical CGAT.

| S-EPMC9299682 | biostudies-literature

Droplet Core Intermolecular Interactions and Block Copolymer Composition Heavily Influence Oil-In-Water Nanoemulsion Stability.

Project description:Colloidal oil-in-water nanoemulsions are gaining increasing interest as a nanoparticle delivery system because of their large oil droplet core that can carry a large payload. In order to formulate these particles with long-term stability, an appropriate oil media and block copolymer pair must be selected. The interaction between the nanoemulsion core and the polymer shell is critical to forming stable nanoparticles. Herein, we probed how interactions between various polymers with hydrocarbon and perfluorocarbon oil media influenced nanoemulsion formation, stability, and size. Through a series of nanoemulsions with unique polymer/oil media combinations, we examined the effects of oil core hydrophobicity, fluorophilicity, surface charge, and volume as well as the effects of polymer tail composition. Surprisingly, we found that nanoemulsions formulated with pure perfluorocarbon oil cores versus perfluoro poly(ether) oil cores exhibited very different characteristics. We also found that both hydrocarbon and fluorocarbon polymer tails interacted favorably with perfluoro poly(ethers) as well as hydrocarbon oil cores forming stable nanoemulsions. We believe these results are focused on the unique properties of perfluorocarbons especially their rigidity, low polarizability, and near-zero surface charge. Interestingly, we saw that perfluoro poly(ethers) deviated from these expected properties resulting in an increased versatility when formulating nanoemulsions with perfluoro poly(ether) oil cores compared to pure perfluorocarbon oil cores. Nanoemulsion size, stability, growth rate, and life time were explored to probe these factors. Experimental and computational data are presented as a rationale.

| S-EPMC7454039 | biostudies-literature

Influence of odd-even effect and intermolecular interactions in 2D molecular layers of bisamide organogelators.

Project description:Organogelators have a wide range of use in everyday life including drug delivery and controlled release, surface coating and paper industry. In this study, a series of model bisamides have been analyzed as potential organogelators. These molecules are connected by odd and even numbered methylene units (n) in length ranging from 2 to 9. By constructing layers of those molecules along the growth direction we provide an insight into the self-assembly process. A complete systematic analysis of the computational results with B3LYP/6-311+G** suggests that the self-assembly of these potential organogelators is influenced by the odd-even effect, the relative direction of amide carbonyl groups, the bridging spacer chain length and the presence of a chiral alpha carbon. The aforementioned factors alter the strength of the intermolecular hydrogen bonds as well as the van der Waals interactions, which in turn may affect the self-assembly process of gelation and result in the formation of aggregates with different shapes. It is found that molecules with short central chains have an energetic preference for antiparallel arrangement over their parallel analogues as a result of stronger hydrogen bonding interactions. As the central chain elongates, the free energy difference between antiparallel and parallel structures decreases suggesting a compromise between hydrogen bonding and van der Waals interactions. The complete structural analysis suggests ribbon-like structures for achiral even-antiparallel and woven-like structures for odd-parallel systems, respectively. Upon creation of asymmetry on the alpha carbon, a twisted ribbon-like and a coiled coil-like structure are observed for even and odd systems, respectively. Our computational results are in accordance with the experimental results and provide an insight into the self-assembly of layers of bisamides.

| S-EPMC9088050 | biostudies-literature

Influence of the physiochemical properties of superparamagnetic iron oxide nanoparticles on amyloid ? protein fibrillation in solution.

Project description:Superparamagnetic iron oxide nanoparticles (SPIONs) are recognized as promising nanodiagnostic materials due to their biocompatibility, unique magnetic properties, and their application as multimodal contrast agents. As coated SPIONs have potential use in the diagnosis and treatment of various brain diseases such as Alzheimer's, a comprehensive understanding of their interactions with A? and other amyloidogenic proteins is essential prior to their clinical application. Here we demonstrate the effect of thickness and surface charge of the coating layer of SPIONs on the kinetics of fibrillation of A? in aqueous solution. A size and surface area dependent "dual" effect on A? fibrillation was observed. While lower concentrations of SPIONs inhibited fibrillation, higher concentrations increased the rate of A? fibrillation. With respect to coating charge, it is evident that the positively charged SPIONs are capable of promoting fibrillation at significantly lower particle concentrations compared with negatively charged or uncharged SPIONs. This suggests that in addition to the presence of particles, which affect the concentration of monomeric protein in solution (and thereby the nucleation time), there are also effects of binding on the protein conformation.

| S-EPMC3605812 | biostudies-other

Large Non-planar Conjugated Molecule with Strong Intermolecular Interactions Achieved with Homoleptic Zn(II) Complex of Di(5-quinolylethynyl)-tetraphenylazadipyrromethene.

Project description:Zinc(II) complexes of tetraphenylazadipyrromethenes are potential non-planar n-type conjugated materials. To tune the properties, we installed 5-quinolylethynyl groups at the pyrrolic positions. Compared to the complex with 1-napthylethynyl, we found evidence for stronger intermolecular interactions in the new complex, including much higher overlap integrals in crystals. X-ray analysis revealed unconventional C-H···N hydrogen bonding between two quinolyls of neighboring molecules, pointing to a new strategy for the development of non-planar molecular semiconductors with stronger intermolecular interactions.

| S-EPMC7726932 | biostudies-literature

Physiochemical properties of Caulobacter crescentus holdfast: a localized bacterial adhesive.

Project description:To colonize surfaces, the bacterium Caulobacter crescentus employs a polar polysaccharide, the holdfast, located at the end of a thin, long stalk protruding from the cell body. Unlike many other bacteria which adhere through an extended extracellular polymeric network, the holdfast footprint area is tens of thousands times smaller than that of the total bacterium cross-sectional surface, making for some very demanding adhesion requirements. At present, the mechanism of holdfast adhesion remains poorly understood. We explore it here along three lines of investigation: (a) the impact of environmental conditions on holdfast binding affinity, (b) adhesion kinetics by dynamic force spectroscopy, and (c) kinetic modeling of the attachment process to interpret the observed time-dependence of the adhesion force at short and long time scales. A picture emerged in which discrete molecular units called adhesins are responsible for initial holdfast adhesion, by acting in a cooperative manner.

| S-EPMC3926197 | biostudies-literature

Physiochemical properties and probiotic survivability of symbiotic oat-based beverage.

Project description:The objectives of this study were to develop a symbiotic oat-based beverage (SOB) and to analyze its physiochemical properties and the probiotic survivability. The beverage base was prepared by fermenting a mix containing oat flour (10%, w/w), sugar (4%, w/w), and inulin (1%, w/w) with a commercial Lactobacillus plantarum (0.003%, w/w) at 30 °C for 12 h. The SOB was formulated using the fermented oat base, sugar, stabilizers (pectin and λ-carrageenan), vitamin C, and citric acid. The beverage was analyzed for total solids (11.65 ± 0.22%), protein (0.58 ± 0.02%), fat (0.37 ± 0.02%), carbohydrate (10.70 ± 0.33%), ash (0.14 ± 0.01%), and dietary fiber (0.70 ± 0.05%). The pH value of the beverage was stable at about 3.60 during 7-week storage. Lactobacillus plantarum population in the beverage remained above 107 CFU/g throughout the storage. Oat-based beverage is a low fat and high dietary fiber symbiotic food.

| S-EPMC6049662 | biostudies-literature

Advanced Insights into Walnut Protein: Structure, Physiochemical Properties and Applications.

Project description:Facing extreme pressure from an increasing population and climate degeneration, it is important to explore a green, safe and environmentally sustainable food source, especially for protein-enriched diets. Plant proteins have gained much attention in recent years, ascribing to their high nutritional value and environmental friendliness. In this review, we summarized recent advances in walnut protein with respect to its geographical distribution, structural and physiochemical properties and functional attributes. As a worldwide cultivated and largely consumptive crop, allergies and some physicochemical limitations have also led to a few concerns about walnut protein. Through comprehensive analysis and discussion, some strategies may be useful for future research, extraction and processing of walnut protein.

| S-EPMC10572233 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data