Month: December 2022

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

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

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

Jeong, Heeseok published the artcilePreparation and drug release behavior of nifedipine-loaded poly(lactic acid)/polyethylene glycol microcapsules, Formula: C17H18N2O6, the main research area is nifedipine polylactic acid polyethylene glycol microcapsule drug release behavior.

Nifedipine (NF)-loaded poly(lactic acid) (PLA) and PLA/polyethylene glycol (PLA/PEG) microcapsules are synthesized using a high-speed agitator and a syringe pump with an oil-in-water emulsion-solvent evaporation technique to evaluate the effect of PLA/PEG ratio on morphol. and drug release behavior of the capsules. Fourier transform IR spectroscopy (FT-IR), differential scanning calorimeter (DSC), and X-ray diffraction (XRD) results indicate that PEG reacts successfully with PLA due to the ether bond between PEG and PLA. The drug release rate of PLA and PLA/PEG capsules increases dramatically from 0 to 5 min and then reaches a plateau within 15 to 20 min. Due to the high sp. surface area, the amount of NF released is raised by reducing the PLA concentration from 5 wt% to 2 wt%. Unlike PLA capsules, the drug release rate of PLA/PEG capsules increases due to the size effect by varying the PLA/PEG ratio from 10/0 to 6/4. Larger PLA/PEG capsules are attributed to higher amounts of encapsulated NF. The capsules show no evidence of cytotoxicity, suggesting that the PLA and PLA/PEG drug carriers are clin. safe.

Journal of Nanoscience and Nanotechnology published new progress about Cytotoxicity. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Formula: C17H18N2O6.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

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

Ge, Xin published the artcileA concise synthesis of 2-chloro-3-amino-4-methylpyridine, Application In Synthesis of 133627-45-9, the main research area is pyridinamine chloro methyl preparation.

An improved and com. valuable process is developed for the scalable synthesis of 2-chloro-3-amino-4-methylpyridine [CAPIC, a key intermediate of Nevirapine]. The synthesis was accomplished in four steps, featuring a condensation reaction starting from 4,4-dimethoxy-2-butanone and cyanoacetamide with ammonium acetate and acetic acid as catalyst. The total yield of the process is 62.1%. The pure CAPIC sample was confirmed with FTIR, 1H-NMR and 13C-NMR.

Research on Chemical Intermediates published new progress about Chlorination. 133627-45-9 belongs to class pyridine-derivatives, name is 2-Chloro-4-methylpyridin-3-amine, and the molecular formula is C6H7ClN2, Application In Synthesis of 133627-45-9.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Ravasenga, Tiziana published the artcileSpatial regulation of coordinated excitatory and inhibitory synaptic plasticity at dendritic synapses, Name: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is synaptic plasticity dendritic synapses; GABA uncaging; GABAergic synaptic plasticity; calcium imaging; dendrites; gephyrin; glutamate uncaging; glutamatergic spines; glutamatergic synaptic plasticity; heterosynaptic plasticity; receptor lateral diffusion.

The induction of synaptic plasticity at an individual dendritic glutamatergic spine can affect neighboring spines. This local modulation generates dendritic plasticity microdomains believed to expand the neuronal computational capacity. Here, we investigate whether local modulation of plasticity can also occur between glutamatergic synapses and adjacent GABAergic synapses. We find that the induction of long-term potentiation at an individual glutamatergic spine causes the depression of nearby GABAergic inhibitory synapses (within 3 μm), whereas more distant ones are potentiated. Notably, L-type calcium channels and calpain are required for this plasticity spreading. Overall, our data support a model whereby input-specific glutamatergic postsynaptic potentiation induces a spatially regulated rearrangement of inhibitory synaptic strength in the surrounding area through short-range heterosynaptic interactions. Such local coordination of excitatory and inhibitory synaptic plasticity is expected to influence dendritic information processing and integration.

Cell Reports published new progress about Brain cortex. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Name: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Dilip, Kinkar Viki published the artcileResearch article on to investigate, develop and evaluate pharmaceutical excipient from orange peel powder, Application In Synthesis of 72509-76-3, the main research area is orange peel powder pharmaceutical excipient.

The present study aimed to investigate, develop and evaluate pharmaceutical excipients from orange peel powder and assess its binding property in tablets by using perindopril erbumine as a modal drug. Now a day′s synthetic polymers are mostly used in the pharmaceutical industry they have many disadvantages such as harmful effects on the human body, highly costly but recently natural polymers are used as a pharmaceutical application like orange peel waste material is used as an excipient have many advantages such as nontoxic, nonirritants easily available, it is economically and biocompatible. There are two basic categories of orange: sweet orange and bitter orange. Orange peel consists of several important constituents such as limonene, citral, vitamin c, hesperidin, and pectin are used as pharmaceutical additives. Manufacturing of tablets was done by using direct compression method on lab level tablet press (CEMACH) by direct compression method. Evaluations tests performed on tablets such as Hardness, Weight variation, friability, disintegration test, etc.

International Journal of Pharmacy and Pharmaceutical Research published new progress about Body remains. 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 In Synthesis of 72509-76-3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Du, Congwu published the artcileCa2+ channel blockade reduces cocaine′s vasoconstriction and neurotoxicity in the prefrontal cortex, SDS of cas: 21829-25-4, the main research area is calicum channel blockade cocaine vasoconstriction neurotoxicity prefrontal cortex.

Cocaine profoundly affects both cerebral blood vessels and neuronal activity in the brain. The vasoconstrictive effects of cocaine, concurrently with its effects on neuronal [Ca2+]i accumulation are likely to jeopardize neuronal tissue that in the prefrontal cortex (PFC) could contribute to impaired self-regulation and compulsive cocaine consumption. Here we used optical imaging to study the cerebrovascular and neuronal effects of acute cocaine (1 mg/kg i.v.) and to examine whether selective blockade of L-type Ca2+ channels by Nifedipine (NIF) (0.5 mg/kg i.v.) would alleviate cocaine′s effects on hemodynamics (measured with cerebral blood volume, HbT), oxygenation (measured with oxygenated Hb, HbO2) and neuronal [Ca2+]i, which were concomitantly measured in the PFC of naive rats. Our results show that in the PFC acute cocaine significantly reduced flow delivery (HbT), increased neuronal [Ca2+]i accumulation and profoundly reduced tissue oxygenation (HbO2) and these effects were significantly attenuated by NIF pretreatment. They also show that cocaine-induced vasoconstriction is distinct from its increase of neuronal [Ca2+]i accumulation though both of them contribute to hypoxemia and both effects were attenuated by NIF. These results provide evidence that blockade of voltage-gated L-type Ca2+ channels might be beneficial in preventing vasoconstriction and neurotoxic effects of cocaine and give support for further clin. investigations to determine their value in reducing cocaine′s neurotoxicity in cocaine use disorders.

Translational Psychiatry published new progress about Blood volume. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, SDS of cas: 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Kim, BaRun published the artcileA differentiated Ca2+ signalling phenotype has minimal impact on myocardin expression in an automated differentiation assay using A7r5 cells, Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is signalling phenotype myocardin expression vascular smooth muscle cell A7r5; Differentiation; High-content analysis; ImageJ; Microscopy; Smooth muscle.

Vascular smooth muscle cells are unusual in that differentiated, contractile cells possess the capacity to “”de-differentiate”” into a synthetic phenotype that is characterized by being replicative, secretory, and migratory. One aspect of this phenotypic modulation is a shift from voltage-gated Ca2+ signalling in elec. coupled, differentiated cells to increased dependence on store-operated Ca2+ entry and sarcoplasmic reticulum Ca2+ release in synthetic cells. Conversely, an increased voltage-gated Ca2+ entry is seen when proliferating A7r5 smooth muscle cells quiesce. We asked whether this change in Ca2+ signalling was linked to changes in the expression of the phenotype-regulating transcriptional co-activator myocardin or α-smooth muscle actin, using correlative epifluorescence Ca2+ imaging and immunocytochem. Cells were cultured in growth media (DMEM, 10% serum, 25 mM glucose) or differentiation media (DMEM, 1% serum, 5 mM glucose). Coinciding with growth arrest, A7r5 cells became elec. coupled, and spontaneous Ca2+ signalling showed increasing dependence on L-type voltage-gated Ca2+ channels that were blocked with nifedipine (5 μM). These synchronized oscillations were modulated by ryanodine receptors, based on their sensitivity to dantrolene (5 μM). Actively growing cultures had spontaneous Ca2+ transients that were insensitive to nifedipine and dantrolene but were blocked by inhibition of the sarco-endoplasmic reticulum ATPase with cyclopiazonic acid (10 μM). In cells treated with differentiation media, myocardin and αSMA immunoreactivity increased prior to changes in the Ca2+ signalling phenotype, while chronic inhibition of voltage-gated Ca2+ entry modestly increased immunoreactivity of myocardin. Stepwise regression analyzes suggested that changes in myocardin expression had a weak relationship with Ca2+ signalling synchronicity, but not frequency or amplitude. In conclusion, we report a 96-well assay and anal. pipeline to study the link between Ca2+ signalling and smooth muscle differentiation. This assay showed that changes in the expression of two mol. differentiation markers (myocardin and αSMA) tended to precede changes in the Ca2+ signalling phenotype.

Cell Calcium published new progress about Blood vessel. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem