Tag: M.W=350-400

Wise, L. David published the artcileIvermectin for COVID-19: Concerns during pregnancy, Synthetic Route of 72509-76-3, the main research area is polemic COVID 19 ivermectin pregnancy.

A polemic in response to Nicolas et al ( Lancet Glob. Health 8 (2020) e92-100) is given. The author Nicolas et al reviewed the safety of oral ivermectin during human pregnancy and concluded there was insufficient evidence of safety. According to product labeling, ivermectin produced an increase in malformations when given to pregnant mice at less than the human dose on a body surface area basis. The lowest teratogenic dose levels for animals in the 1996 NDA for ivermectin (NDA 50-742) are 0.4 mg/kg/day in mice, 3 mg/kg/day in rabbits, and 10 mg/kg/day in rats. Fetal-placental units deficient in P-glycoprotein were 100% susceptible to cleft palate, while fetuses with full P-glycoprotein expression had 0% cleft palate. A different outbred mouse strain with full P-glycoprotein expression showed no defects at the highest tested dose level (3 mg/kg/day of a related photoisomer). Similarly, as the aforementioned studies of the NDA reported, rats and rabbits required somewhat higher ivermectin doses to induce birth defects due to their full P-glycoprotein expression. Thus, besides the lack of adequate clin. safety of ivermectin in human pregnancies, healthcare providers should be aware of the animal data as an under-appreciated potential risk factor to pregnant women who take ivermectin for Covid-19. A number of coadministration studies in various species have shown increased systemic exposure, organ concentrations, or toxicity of ivermectin. The combination will likely cause an increased level of ivermectin in the developing embryo or fetus, potentially inducing birth defects.

Reproductive Toxicology published new progress about Cleft palate. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, Synthetic Route of 72509-76-3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Saboo, Sugandha published the artcilePatterns of drug release as a function of drug loading from amorphous solid dispersions: A comparison of five different polymers., Application of 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is felodipine polyvinylpyrrolidone hydroxypropylmethylcellulose acetate succinate nilvadipine cilnidipine chlorine; Amorphous solid dispersions; Congruent; Drug release; Hydrophobicity; Phase separation; Polymer release.

The aim of this study was to comprehensively evaluate drug release mechanisms from ASDs with polymers of varying hydrophobicity as a function of drug loading. Surface normalized dissolution rates of drug and polymer were studied for felodipine ASDs with polyvinylpyrrolidone, polyvinylpyrrolidone/vinyl acetate (PVPVA), Eudragit S 100 (EUDS), hydroxypropylmethylcellulose and hydroxypropylmethylcellulose acetate succinate as a function of drug loading. The water sorption profiles and water contact angle measurements suggested the following rank order for hydrophobicity of the different polymers: HPMCAS ≃ EUDS > HPMC > PVPVA > PVP. For ASDs with more hydrophobic polymers (HPMCAS and EUDS), the dissolution rate of both drug and polymer was polymer-controlled for drug loadings as high as 50%, with a more gradual decline in drug release rate at higher drug loadings. Notably, at low drug loadings and across the different polymers, when the polymer dictated the drug release rate, ASDs prepared with the most hydrophilic polymers showed the fastest drug release. This suggested a trade-off in choosing between higher release rates with more hydrophilic polymers at low drug loadings and higher drug loadings achievable with more hydrophobic polymers at the expense of lowered release rates. The findings described herein have significant implications for rational selection of polymers for formulation of ASDs with high drug loading and enhanced dissolution performance.

European Journal of Pharmaceutical Sciences published new progress about Drugs (EUDS). 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, Application of 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Yang, Haonan published the artcileEffect of Dihydropyridine Enrichment in the Microstructure of the Palisade Layer on the Stability of Fat Nano-emulsions, Quality Control of 72509-76-3, the main research area is dihydropyridine felodipine palisade layer particle size stability fat nanoemulsion; Fat nano-emulsion; Felodipine; Nimodipine; Nuclear magnetic resonance; Palisade layer; Stability.

Relationship between the stability of fat nano-emulsions and the incorporated drug at the mol. level are rarely known. Herein, fat nano-emulsions containing dihydropyridine drugs were prepared and the microstructure of their palisade layers were investigated.The prepared 1.0 mg/mL nimodipine nano-emulsion was found to contain 65.50% drug in the palisade layer. The increasing drug concentration led to a decrease-increase-decrease trend in centrifugal stability constant, particle size and proton NMR (1H NMR) signal intensity of the lecithin tri-Me ammonium group in the nimodipine and felodipine nano-emulsions. The 1H NMR spectra of test solutions including nano-emulsions suggest that increasing drugs penetrated into the palisade layer, resulting in the lecithin arrangement from loose to tight, and then from monolayer to bilayer. Nimodipine and felodipine nano-emulsions showed two valley values at concentrations of 0.15 and 0.75 mg/mL, and 0.30 and 0.90 mg/mL resp., which indicated that the nano-emulsion has two more stable states corresponding to the tightly arranged mono- and bi-palisade layer. These two concentrations are pos. correlated with lipophilicity of nimodipine and felodipine. Further, nimodipine liposomes were prepared to validate the effect of drugs on the arrangement of lecithin in the palisade layer. 1H NMR characterizations of the liposomes showed a similar profile to that of nano-emulsions. These results demonstrated that the increasing drug concentration could cause a rearrangement of lecithin in the palisade layer, thus affecting emulsion stability.

Journal of Pharmaceutical Sciences (Philadelphia, PA, United States) published new progress about Formulations. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, Quality Control of 72509-76-3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

McPherson, Stephanie published the artcileSmall scale design of experiment investigation of equilibrium solubility in simulated fasted and fed intestinal fluid, Product Details of C18H19Cl2NO4, the main research area is intestinal juice PH ibuprofen valsartan zafirlukast indomethacin solubility; Biopharmaceutical Classification System; Design of Experiment; Fasted State Simulated Intestinal fluid; Fed State Simulated Intestinal Fluid; Orbito; Solubility.

It is widely recognized that drug solubility within the gastrointestinal tract (GIT) differs from values determined in a simple aqueous buffer and to circumvent this problem measurement in biorelevant fluids is determined Biorelevant fluids are complex mixtures of components (sodium taurocholate, lecithin, sodium phosphate, sodium chloride, pancreatin and sodium oleate) at various concentrations and pH levels to provide systems simulating fasted (FaSSIF) or fed (FeSSIF) intestinal media. Design of Experiment (DoE) studies have been applied to investigate FaSSIF and FeSSIF and indicate that a drugs equilibrium solubility varies over orders of magnitude, is influenced by the drug type and individual or combinations of media components, with some of these interactions being drug specific. Although providing great detail on the drug media interactions these studies are resource intensive requiring up to ninety individual experiments for FeSSIF. In this paper a low sample number or reduced DoE system has been investigated by restricting components with minimal solubility impact to a single value and only investigating variations in the concentrations of sodium taurocholate, lecithin, sodium oleate, pH and addnl. in the case of fed media, monoglyceride. This reduces the experiments required to ten (FaSSIF) and nine (FeSSIF). Twelve poorly soluble drugs (Ibuprofen, Valsartan, Zafirlukast, Indomethacin, Fenofibrate, Felodipine, Probucol, Tadalafil, Carvedilol, Aprepitant, Bromocriptine and Itraconazole) were investigated and the results compared to published DoE studies and literature solubility values in human intestinal fluid (HIF), FaSSIF or FeSSIF. The solubility range determined by the reduced DoE is statistically equivalent to the larger scale published DoE results in over eighty five percent of the cases. The reduced DoE range also covers HIF, FaSSIF or FeSSIF literature solubility values. In addition the reduced DoE provides lowest measured solubility values that agree with the published DoE values in ninety percent of the cases. However, the reduced DoE only identified single and in some cases none of the major components influencing solubility in contrast to the larger published DoE studies which identified multiple individual components and component interactions. The identification of significant components within the reduced DoE was also dependent upon the drug and system under investigation. The study demonstrates that the lower exptl. number reduces statistical power of the DoE to resolve the impact of media components on solubility However, in a situation where only the solubility range is required the reduced DoE can provide the desired information, which will be of benefit during in vitro development studies. Further refinements are possible to extend the reduced DoE protocol to improve biorelevance and application into areas such as PBPK modeling.

European Journal of Pharmaceutics and Biopharmaceutics published new progress about Homo sapiens. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, Product Details of C18H19Cl2NO4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Salunkhe, Nitin published the artcileSericin Inhibits Devitrification of Amorphous Drugs, HPLC of Formula: 72509-76-3, the main research area is lornoxicam meloxicam felodipine sericin devitrification drug stability; amorphous solid dispersions (ASD); devitrification; dissolution; sericin; solubility.

The purpose of the present investigation was to analyze devitrification of amorphous drugs such as lornoxicam, meloxicam, and felodipine in the presence of sericin. The binary solid dispersions comprising varying mass ratios of drug and sericin were subject to amorphization by spray drying, solvent evaporation, ball milling, and phys. mixing. Further, obtained solid dispersions (SDs) were characterized by HPLC, ATR-FTIR, H1NMR, mol. docking, accelerated stability study at 40°C and 75 ± 2% RH (XRD and DSC), and in vitro dissolution studies. The HPLC anal. indicated no decomposition of the drugs during the spray drying process. From ATR-FTIR, NMR, and mol. docking study, it was revealed that H-bonding played a vital role in amorphous drug stabilization. An excellent devitrification inhibition was observed in case of lornoxicam (SDLS3) and meloxicam (SDMS3) SDs prepared by spray drying. On the other hand, spray-dried SD of felodipine (SDFS3) showed traces of microcrystals. The percent crystallinity of SDLS3, SDMS3, and SDFS3 was found to be 7.4%, 8.23%, and 18.31% resp. indicating adequate amorphization. The dissolution performance of SDLS, SDMS, and SDFS after 3 mo showed > 85% than SDs prepared by other methods. Thus, sericin significantly inhibited crystallization and was responsible for amorphous state stabilization of pharmaceuticals.

AAPS PharmSciTech published new progress about Amorphization. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, HPLC of Formula: 72509-76-3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Govender, Rydvikha published the artcileEnabling modular dosage form concepts for individualized multidrug therapy: Expanding the design window for poorly water-soluble drugs, Computed Properties of 72509-76-3, the main research area is multidrug therapy poorly water soluble drug; Amorphous solid dispersions; Flexible combinations; Mass customization; Melt extrusion; Oral drug release; Polypharmacy.

Multidrug dosage forms (aka combination dosage forms, polypills, etc.) create value for patients through reduced pill burdens and simplified administration to improve adherence to therapy. Enhanced flexibility of multidrug dosage forms would provide further opportunities to better match emerging needs for individualized therapy. Through modular dosage form concepts, one approach to satisfy these needs is to adapt multidrug dosage forms to a wider variety of drugs, each with a variety of doses and release profiles. This study investigates and tech. explores design requirements for extending the capability of modular multidrug dosage form concepts towards individualization. This builds on our recent demonstration of independent tailoring of dose and drug release, which is here extended towards poorly water-soluble drugs. The challenging design requirement of carrying higher drug loads in smaller volumes to accommodate multiple drugs at their clin. dose is here met regarding dose and release performance. With a modular concept, we demonstrate high precision (<5% RSD) in dose and release performance of individual modules containing felodipine or naproxen in Kollidon VA64 at both a wide drug loading range (5% weight/weight and 50% weight/weight drug) and a small module size (3.6 mg). In a forward-looking design-based discussion, further requirements are addressed, emphasizing that reproducible individual module performance is predictive of dosage form performance, provided the modules are designed to act independently. Therefore, efforts to incorporate progressively higher drug loads within progressively smaller module volumes will be crucial to extend the design window further towards full flexibility of future dosage forms for individualized multidrug therapy. International Journal of Pharmaceutics (Amsterdam, Netherlands) published new progress about Amorphization. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, Computed Properties of 72509-76-3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Pajzderska, A. published the artcileNMR relaxometry in an investigation of the kinetics of the recrystallization of a three-phase system, SDS of cas: 72509-76-3, the main research area is polyvinylpyrrolidone nuclear magnetic resonances relaxometry recrystallization three phase system; Amorphization; Felodipine; PVP; Physical mixture; Recrystallization; Relaxometry.

The method of 1H NMR (NMR) relaxometry is applied to investigate the kinetics of the recrystallization of an active pharmaceutical ingredient (felodipine) from the amorphous phase of its phys. mixture with a polymer (polyvinylpyrrolidone, PVP). Comparison of the recrystallization results obtained for amorphous felodipine and its mixtures with PVP shows that the recrystallization process of API is faster in the mixtures and depends on the content of water in the system. The free induction decay (FID) for protons that were detected are composed of three components, and the loss of water from PVP strongly influences the part characterized by the longest spin-spin lattice relaxation time. Anal. of the FID of the phys. mixture indicates that the content of water does not change during the recrystalization process. The study shows that the T11H NMR relaxometry method is very useful for analyzing the composition of a three-phase mixture and the recrystallization process.

International Journal of Pharmaceutics (Amsterdam, Netherlands) published new progress about Amorphization. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, SDS of cas: 72509-76-3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Ghosh, Arunava published the artcileCellular effects of nicotine salt-containing e-liquids, Related Products of pyridine-derivatives, the main research area is calcium electronic nicotine delivery system macrophage; Ca2+; JUUL; cell; flavor; macrophage; nicotine salt.

“”Pod-based”” e-cigarettes such as JUUL are currently the most prevalent electronic nicotine delivery systems (ENDS) in the United States. JUUL-type ENDS utilize nicotine salts protonated with benzoic acid rather than freebase nicotine. However, limited information is available on the cellular effects of these products. Cytoplasmic Ca2+ is a universal second messenger that controls many cellular functions including cell growth and cell death. Of note, dysregulation of cell Ca2+ homeostasis has been linked with several disease processes including autoimmune disease and several types of cancer. We exposed HEK293T cells and THP-1 macrophage-like cells to different JUUL e-liquids We evaluated their effects on cellular viability and Ca2+ signaling by measuring fluorescence from calcein-AM/propidium iodide and Fluo-4, resp. E-liquid autofluorescence was used to look for e-liquid permeation into cells. To identify the mechanisms behind the Ca2+ responses, different inhibitors of Ca2+ channels and phospholipase C signaling were used. JUUL e-liquids caused significant cytotoxic effects, with””Mint”” flavor being the most cytotoxic. The Mint flavored e-liquid also caused a significant elevation in cytoplasmic Ca2+. Using autofluorescence, the permeation of JUUL e-liquids into live cells was confirmed, indicating that intracellular organelles are directly exposed to e-liquids Further studies identified the endoplasmic reticulum as being the source of e-liquid-induced changes in cytoplasmic Ca2+. Nicotine salt-based e-liquids cause cytotoxicity and elevate cytoplasmic Ca2+, indicating that they can exert biol. effects beyond what would be expected with nicotine alone. These effects are flavor-dependent, and we propose that flavored e-liquids be reassessed for potential lung toxicity.

Journal of Applied Toxicology published new progress about Cell adhesion. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, Related Products of pyridine-derivatives.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Guan, Jian published the artcileSynergetic effect of nucleation and crystal growth inhibitor on in vitro-in vivo performance of supersaturable lacidipine solid dispersion, HPLC of Formula: 72509-76-3, the main research area is c nucleation crystal growth inhibitor supersaturable lacidipine solid dispersion; Gum arabic; Lacidipine; Solid dispersion; Soluplus; Supersaturation.

Limited supersaturation maintaining duration is the main challenge for amorphous solid dispersion design. Nucleation or crystal growth inhibitors may function in different ways but the combination use of nucleation and crystal growth inhibitors in supersaturated system is rarely explored. Thus, using Lacidipine (LCDP) as a Biopharmaceutical Classification System (BCS) II model drug, the aim of this study was to explore whether the combination use of nucleation and crystal growth inhibitors could provide a synergistic effect on the in vitro-in vivo performance of poorly water-soluble drugs. First of all, based on compatibility screening using solubility parameter (Δδ) and crystallization inhibition efficiency as criteria, soluplus (SOL) and gum arabic (GA) were selected as the most effective nucleation and crystal growth inhibitor resp. Thereafter, the supersaturated drug solutions were spray dried and characterized. The in vitro release, phys. stability as well as pharmacokinetic behavior were investigated. It was found that the combination use of SOL and GA did not present remarkable advantage in prolonging the supersaturation time in solution state. However, their synergistic effect in equilibrium solubility and dissolution enhancement was noticed at SOL/GA ratio 3:1, with 5-7 times higher dissolution rate observed for LCDP/SOL/GA based formulation compared with that of LCDP/SOL, which was maintained even after three months accelerated stability test under non-sink condition. Moreover, compared to the LCDP/SOL formulation, approx. 2.8 and 2.5-fold increase in the maximum plasma concentration (Cmax) and the area under the plasma-time curve (AUC0-∞) was achieved with LCDP/SOL/GA based formulation. Possible mechanism of the synergistic effect was elucidated, indicating GA may penetrate into SOL particles providing both electrostatic and steric stabilization. In conclusion, the combination use of screened nucleation and crystal growth inhibitors might be an efficient approach to design supersaturated drug delivery system.

International Journal of Pharmaceutics (Amsterdam, Netherlands) published new progress about Crystal growth. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, HPLC of Formula: 72509-76-3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Chen, Yinshan published the artcileEffect of molecular size and hydrogen bonding on three surface-facilitated processes in molecular glasses: Surface diffusion, surface crystal growth, and formation of stable glasses by vapor deposition, HPLC of Formula: 72509-76-3, the main research area is mol size hydrogen bonding surface diffusion; crystal growth stable glass vapor deposition.

Recent work has shown that diffusion and crystal growth can be much faster on the surface of mol. glasses than in the interior and that the enhancement effect varies with mol. size and intermol. hydrogen bonds (HBs). In a related phenomenon, some mols. form highly stable glasses when vapor-deposited, while others (notably those forming extensive HBs) do not. Here we examine all available data on these phenomena for quant. structure-property relations. For the systems that form no HBs, the surface diffusion coefficient Ds decreases with increasing mol. size d (d = Ω1/3, where Ω is the mol. volume); when evaluated at the glass transition temperature Tg, Ds decreases ∼5 orders of magnitude for 1 nm of increase in d. Assuming that center-of-mass diffusion is limited by the deepest part of the mol. in the surface-mobility gradient, these data indicate a mobility gradient in reasonable agreement with the Elastically Collective Nonlinear Langevin Equation theory prediction for polystyrene as disjointed Kuhn monomers. For systems of similar d, the Ds value decreases with the extent of intermol. HB, x (HB), defined as the fraction of vaporization enthalpy due to HB. For both groups together (hydrogen-bonded and otherwise), the Ds data collapse when plotted against d/[1 – x(HB)]; this argues that the HB effect on Ds can be described as a narrowing of the surface mobility layer by a factor [1 – x(HB)] relative to the van der Waals systems. Essentially the same picture holds for the surface crystal growth rate us. The kinetic stability of a vapor-deposited glass decreases with x(HB) but is not better organized by the combined variable d/[1 – x(HB)]. These results indicate that surface crystal growth depends strongly on surface diffusion, whereas the formation of stable glasses by vapor deposition may depend on other factors. (c) 2019 American Institute of Physics.

Journal of Chemical Physics published new progress about Crystal growth. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, HPLC of Formula: 72509-76-3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem