Category: 72509-76-3

Yu, Yong-Jie published the artcileAutomatic data analysis workflow for ultra-high performance liquid chromatography-high resolution mass spectrometry-based metabolomics, COA of Formula: C18H19Cl2NO4, the main research area is automatic data analysis algorithm UHPLC HRMS metabolomics; Automatic data analysis; Chemometrics; MATLAB GUI; UPLC-HRMS; Untargeted metabolomics.

Data anal. for ultra-performance liquid chromatog. high-resolution mass spectrometry-based metabolomics is a challenging task. The present work provides an automatic data anal. workflow (AntDAS2) by developing three novel algorithms, as follows: (i) a d.-based ion clustering algorithm is designed for extracted-ion chromatogram extraction from high-resolution mass spectrometry; (ii) a new maximal value-based peak detection method is proposed with the aid of automatic baseline correction and instrumental noise estimation; and (iii) the strategy that clusters high-resolution m/z peaks to simultaneously align multiple components by a modified dynamic programing is designed to efficiently correct time-shift problem across samples. Standard compounds and complex datasets are used to study the performance of AntDAS2. AntDAS2 is better than several state-of-the-art methods, namely, XCMS Online, Mzmine2, and MS-DIAL, to identify underlying components and improve pattern recognition capability. Meanwhile, AntDAS2 is more efficient than XCMS Online and Mzmine2. A MATLAB GUI of AntDAS2 is designed for convenient anal. and is available at the following webpage: http://software.tobaccodb.org/software/antdas2.

Journal of Chromatography A published new progress about Algorithm. 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, COA of Formula: C18H19Cl2NO4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Zadymova, N. M. published the artcileAdsorption of a Lipophilic Drug, Felodipine, at Different Interfaces, COA of Formula: C18H19Cl2NO4, the main research area is adsorption lipophilic drug felodipine different interface.

In connection with the development of methods for the delivery of lipophilic drugs in a bioavailable form, we have employed an integrated approach to the investigation of the adsorption of an antihypertensive drug, felodipine, at interfaces that simulate the surfaces of different carriers. Isotherms have been plotted for felodipine adsorption from solutions in heptane (C = 2.13 x 10-5 – 4.26 x 10-4 M) at interfaces with water and silver metal, as well as for the compression of drug monolayers formed on a water surface from the heptane solutions The quant. characteristics of the studied felodipine layers have been determined, and their phase state and the most probable conformation of adsorbed drug mols. have been analyzed taking into account the data of mol. dynamics simulations. The phase state of the felodipine layers at the heptane/water interface is adequately described by the van Laar equation. A bilayer is formed at the silver surface. A phase transition from a gaseous state to a liquid-expanded state has been revealed for the felodipine layers.

Colloid Journal published new progress about Adsorption. 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, COA of Formula: C18H19Cl2NO4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Lin, Yi-Sian published the artcileGWAS Meta-Analysis Reveals Shared Genes and Biological Pathways between Major Depressive Disorder and Insomnia, SDS of cas: 72509-76-3, the main research area is major depressive disorder insomnia gene biol pathway metaanalysis; GWAS; MDD; STRING; comorbidity; eQTL; gene network; insomnia; meta-analysis.

Major depressive disorder (MDD) is one of the most prevalent and disabling mental disorders worldwide. Among the symptoms of MDD, sleep disturbance such as insomnia is prominent, and the first reason patients may seek professional help. However, the underlying pathophysiol. of this comorbidity is still elusive. Recently, genome-wide association studies (GWAS) have begun to unveil the genetic background of several psychiatric disorders, including MDD and insomnia. Identifying the shared genomic risk loci between comorbid psychiatric disorders could be a valuable strategy to understanding their comorbidity. This study seeks to identify the shared genes and biol. pathways between MDD and insomnia based on their shared genetic variants. First, we performed a meta-anal. based on the GWAS summary statistics of MDD and insomnia obtained from Psychiatric Genomics Consortium and UK Biobank, resp. Next, we associated shared genetic variants to genes using two gene mapping strategies: (a) positional mapping based on genomic proximity and (b) expression quant. trait loci (eQTL) mapping based on gene expression linkage across multiple tissues. As a result, a total of 719 shared genes were identified. Over half (51%) of them are protein-coding genes. Functional enrichment anal. shows that the most enriched biol. pathways are related to epigenetic modification, sensory perception, and immunol. signatures. We also identified druggable targets using a network approach. Together, these results may provide insights into understanding the genetic predisposition and underlying biol. pathways of comorbid MDD and insomnia symptoms.

Genes published new progress about Cerebellum. 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

Brinkmann, Joscha published the artcileIn-Silico Screening of Lipid-Based Drug Delivery Systems, Application In Synthesis of 72509-76-3, the main research area is lipid based drug delivery system screening formulation; PC-SAFT; lipid-based formulations; solubility; thermodynamic modeling.

This work proposes an in-silico screening method for identifying promising formulation candidates in complex lipid-based drug delivery systems (LBDDS). The approach is based on a min. amount of exptl. data for API solubilites in single excipients. Intermol. interactions between APIs and excipients as well as between different excipients were accounted for by the Perturbed-Chain Statistical Associating Fluid Theory. The approach was applied to the in-silico screening of lipid-based formulations for ten model APIs (fenofibrate, ibuprofen, praziquantel, carbamazepine, cinnarizine, felodipine, naproxen, indomethacin, griseofulvin and glibenclamide) in mixtures of up to three out of nine excipients (tricaprylin, Capmul MCM, caprylic acid, Capryol 90, Lauroglycol FCC, Kolliphor TPGS, polyethylene glycol, carbitol and ethanol). For eight out of the ten investigated model APIs, the solubilities in the final formulations could be enhanced by up to 100 times compared to the solubility in pure tricaprylin. Fenofibrate, ibuprofen, praziquantel, carbamazepine are recommended as type I formulations, whereas cinnarizine and felodipine showed a distinctive solubility gain in type II formulations. Increased solubility was found for naproxen and indomethacin in type IIIb and type IV formulations. The solubility of griseofulvin and glibenclamide could be slightly enhanced in type IIIb formulations. The exptl. validation agreed very well with the screening results. The API solubility individually depends on the choice of excipients. The proposed in-silico-screening approach allows formulators to quickly determine most-appropriate types of lipid-based formulations for a given API with low exptl. effort.

Pharmaceutical Research published new progress about Cosolvents. 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

Dantonio, Alyssa L. published the artcileIntersystem extrapolation factors are substrate-dependent for CYP3A4: impact on cytochrome P450 reaction phenotyping, Recommanded Product: 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is intersystem extrapolation factor CYP3A4 reaction phenotyping pharmacokinetics.

The use of intersystem extrapolation factors (ISEF) is required for the quant. scaling of drug metabolism data generated in individually expressed cytochrome P 450 (CYP) enzymes when estimating fractional contribution (fm) to metabolism by P 450 enzymes in vivo. For successful prediction of fm, ISEF values must be universal across all substrates for any individual enzyme. In this study, ISEF values were generated for ten CYP3A4 selective substrates using a common source of recombinant heterologously expressed CYP3A4 (rCYP) and a pool of human liver microsomes. The resulting ISEF values for CYP3A4 were substrate-dependent and ranged 8-fold, with the highest value generated from intrinsic clearance of midazolam depletion (0.36) and the lowest from quinidine depletion (0.044). Application of these ISEF values for estimation of the fractional contribution of CYP3A4 and CYP2C19 to omeprazole clearance yielded values that ranged from 0.21-0.63 and 0.37-0.79, resp., as compared with back-extrapolated in vivo fm values of 0.27 (CYP3A4) and 0.85 (CYP2C19) from clin. pharmacokinetic data. For risperidone, estimated fm values for CYP3A4 and CYP2D6 ranged from 0.87-0.98 and 0.02-0.13, resp., as compared with in vivo values of 0.36 (CYP3A4) and 0.63-0.88 (CYP2D6), showing that the importance of CYP3A4 was overestimated, and the importance of CYP2D6 underestimated. Overall, these findings suggest that ISEF values for CYP3A4 can vary with the marker substrate used to derive them, thereby reducing the effectiveness of the approach of using metabolism data from rCYP3A4 with ISEF values for the prediction of fraction metabolized values in vivo.

Drug Metabolism & Disposition published new progress about Hepatocyte. 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, Recommanded Product: 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Alshahrani, Saad M. published the artcileEffect of lutrol F grades (poloxamer) on dissolution of hot-melt extruded Kollidon VA64-felodipine matrices, Application In Synthesis of 72509-76-3, the main research area is felodipine poloxamer lutrol F grade dissolution hot melt extrusion.

The objective of this study was to assess the potential of Lutrol F grades as polymeric surfactants for dissolution enhancement of Kollidon VA64-drug matrixes produced by hot-melt extrusion (HME). The poorly soluble model drug felodipine (FEL) with a medium m.p. was selected for this study. Two different grades of Lutrol F (also called Kolliphor P grades) were added into the HME systems to investigate their influence on the drug-incorporated matrixes. Two grades of Lutrols i.e., Lutrol F 68 (KolliphorP 188) and Lutrol F 127 (KolliphorP 407) were studied as polymeric solubilizers. FEL was mixed with KollidonVA64, with or without LutrolF (alone or in combination) at predetermined amounts which resulted in 8 different formulations. Each blend was melt-extruded at the same extrusion conditions. Differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) analyses were performed to evaluate their physicochem. properties. DSC and PXRD studies suggested the formation of amorphous solid dispersion for all extruded formulations. Dissolution studies revealed that the extrudates with Lutrol F grades exhibited faster and higher release compared to formulations without Lutrol F grades. Formulations with high drug loading, which did not include Lutrol F grades, demonstrated low drug release profiles when compared with the same formulations containing Lutrol F grades. Fourier transform IR (FTIR) studies suggested that a stronger hydrogen bond has occurred between the (-NH) of FEL and (C = O) of the pyrrolidone group in Kollidon VA 64. Overall, these studies suggested the potential of Lutrols in enhancing the dissolution rate of poorly soluble model drug FEL.

Acta Poloniae Pharmaceutica published new progress about Dissolution. 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

Bochmann, Esther S. published the artcileMicro-scale solubility assessments and prediction models for active pharmaceutical ingredients in polymeric matrices, Quality Control of 72509-76-3, the main research area is polyvinylpyrrolidone polyvinyl acetate active pharmaceutical ingredient; Amorphous solid dispersion; Bisacodyl (PubChem CID: 2391); Carbamazepine (PubChem CID: 2554); Celecoxib (PubChem CID: 2662); Cilostazol (PubChem CID: 2754); Clozapine (PubChem CID: 2818); Copovidone (PubChem CID: 25086-89-9); Data review; Dipyridamole (PubChem CID: 3108); Felodipine (PubChem CID: 3333); Gliclazide (PubChem CID: 3475); Griseofulvin (PubChem CID: 441140); Indomethacin (PubChem CID: 3715); Itraconazole (PubChem CID: 55283); Lamotrigine (PubChem CID: 3878); Loratadine (PubChem CID: 3957); Naproxen (PubChem CID: 156391); Nifedipine (PubChem CID: 4485); Posaconazole (PubChem CID: 468595); Praziquantel (PubChem CID: 4891); Prediction model; Probucol (PubChem CID: 4912); Ritonavir (PubChem CID: 392622); Solubility; Telmisartan (PubChem CID: 65999); Verapamil-HCl (PubChem CID: 62969).

The number of models for assessing the solubility of active pharmaceutical ingredients (APIs) in polymeric matrixes on the one hand and the extent of available associated data on the other hand has been rising steadily in the past few years. However, according to our knowledge an overview on the methods used for prediction and the resp. exptl. data is missing. Therefore, we compiled exptl. data, the techniques used for their determination and the models used for estimating the solubility Our focus was on polymers commonly used in spray drying and hot-melt extrusion to form amorphous solid dispersions (ASDs), namely polyvinylpyrrolidone grades (PVP), polyvinyl acetate (PVAc), vinylpyrrolidone-vinyl acetate copolymer (copovidone, COP), polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft polymer (Soluplus, SOL), different types of methacrylate copolymers (PMMA), polyethylene glycol grades (PEG) and hydroxypropyl-methylcellulose grades (HPMC). The literature data were further supplemented by our own results. The final data set included 37 APIs and two sugar derivatives The majority of the prediction models was constituted by the m.p. depression method, dissolution endpoint measurements, indirect solubility determination by Tg and the use of low mol. weight analogs. We observed that the API solubility depended more on the working group which conducted the experiments than on the measuring technique used. Furthermore, this compilation should assist researchers in choosing a prediction method suited for their investigations. Furthermore, a statistical assessment using recursive feature elimination was performed to identify descriptors of mols., which are connected to the API solubility in polymeric matrixes. It is capable of predicting the criterium 20% API soluble at 100°C (Yes/No) for an unknown compound with a balanced accuracy of 71%. The identified 8 descriptors to be connected to API solubility in polymeric matrixes were the number of hydrogen bonding donors, three descriptors related to the hydrophobicity of the mol., glass transition temperature, fractional neg. polar van der Waals surface area, out-of-plane potential energy and the fraction of rotatable bonds. Finally, in addition to our own model, the data set should help researchers in training their own solubility prediction models.

European Journal of Pharmaceutics and Biopharmaceutics published new progress about Flexibility. 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

Lu, Yang published the artcileEnhanced felodipine dissolution from high drug loading amorphous solid dispersions with PVP/VA and sodium dodecyl sulfate, Application In Synthesis of 72509-76-3, the main research area is felodipine dissolution amorphous solid dispersion sodium dodecyl sulfate PVP.

The objective of this study was to investigate the mechanisms of sodium dodecyl sulfate (SDS) and Copovidone (PVP/VA) enhancing the dissolution of high loaded felodipine (FLDP) amorphous extrudates. The rheol. results indicated that PVP/VA inhibited FLDP crystallization and the binary FLDP-PVP/VA (1:1 and 1:3) and ternary FLDP-PVP/VA-SDS (1:1:0.02-0.16 and 1:3:0.02-0.32) extrudates were amorphous solid dispersions (ASDs). Internal SDS (5%-20%) decreased glass transition temperature (Tgs) of FLDP-PVP/VA ternary ASDs. The enhanced dissolution rate of binary or ternary PVP/VA-rich ASDs in the non-sink condition of 0.05%SDS was achieved. SDS enhanced the dissolution of PVP/VA-rich ASDs via wettability and complexation with PVP/VA to accelerate the medium uptake and erosion kinetics of extrudates, but induced FLDP recrystallization and resulted in incomplete dissolution of FLDP-rich extrudates. Interestingly, when the ratio of FLDP-SDS was 1:0.08-0.12, the addition of SDS can significantly promote drug dissolution To confirm the in vitro relevance of these mol. interaction mechanisms, we prepared two tablet formulations which internal or external added SDS, resp., the ratio of FLDP-SDS was 1:0.1. The results show that SDS can promote the dissolution of FLDP when only SDS was internal added.

Journal of Drug Delivery Science and Technology published new progress about Absorption. 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

Premkumar, B. published the artcileFormulation and evaluation of Felodipine hollow microspheres, Application of 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is blood pressure heart stroke felodipine hollow microsphere biocompatibility stability.

Felodipine is a calcium channel blocker which is used for the treatment of high blood pressure to prevent heart stroke. In the current research work hollow microspheres of Felodipine with better absorption in gastric pH was formulated by using various polymers. Drug polymer compatibility was characterized by FT-IR. Microspheres were prepared by emulsion solvent diffusion technique by using different polymers such as Et cellulose, carbopol 934, eudragit and sodium alginate at varying concentrations The formulations were evaluated for micromeritic properties, buoyancy, percentage yield, entrapment efficiency, in vitro studies and stability stuides. SEM photographs showed outer surface of microspheres was smooth and dense where as internal surface was porous which helped to prolong floating. Optimized F2 formulation exhibited higher release rate 95.55%. In vitro drug release studies showed controlled release of Felodipine for over 8h. Stability studies indicated the F2 formulation was stable with respect to its drug release.

European Journal of Biomedical and Pharmaceutical Sciences published new progress about Absorption. 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

Hedge, Oliver J. published the artcileInvestigation of Self-Emulsifying Drug-Delivery System Interaction with a Biomimetic Membrane under Conditions Relevant to the Small Intestine, Safety of 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is small intestine self emulsifying drug delivery system biomimetic membrane.

Self-emulsifying drug-delivery systems (SEDDS) have been extensively shown to increase oral absorption of solvation-limited compounds However, there has been little clin. and com. use of these formulations, in large part because the demonstrated advantages of SEDDS have been outweighed by our inability to precisely predict drug absorption from SEDDS using current in vitro assays. To overcome this limitation and increase the biol. relevancy of in vitro assays, an absorption function can be incorporated using biomimetic membranes. However, the effects that SEDDS have on the integrity of a biomimetic membrane are not known. In this study, a quartz crystal microbalance with dissipation monitoring and total internal reflection fluorescence microscopy were employed as complementary methods to in vitro lipolysis-permeation assays to characterize the interaction of various actively digested SEDDS with a liquescent artificial membrane comprising lecithin in dodecane (LiDo). Observations from surface anal. showed that interactions between the digesting SEDDS and LiDo membrane coincided with inflection points in the digestion profiles. Importantly, no indications of membrane damage could be observed, which was supported by flux profiles of the lipophilic model drug felodipine (FEL) and impermeable marker Lucifer yellow on the basal side of the membrane. There was a correlation between the digestion kinetics of the SEDDS and the flux of FEL, but no clear correlation between solubilization and absorption profiles. Membrane interactions were dependent on the composition of lipids within each SEDDS, with the more digestible lipids leading to more pronounced interactions, but in all cases, the integrity of the membrane was maintained. These insights demonstrate that LiDo membranes are compatible with in vitro lipolysis assays for improving predictions of drug absorption from lipid-based formulations.

Langmuir published new progress about Absorption. 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, Safety of 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem