Category: 72509-76-3

Asano, Satoshi published the artcileA new intestinal model for analysis of drug absorption and interactions considering physiological translocation of contents, Application of 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is midazolam drug absorption interaction intestinal model pharmacotherapy.

Precise prediction of drug absorption is key to the success of new drug development and efficacious pharmacotherapy. In this study, we developed a new absorption model, the advanced translocation model (ATOM), by extending our previous model, the translocation model. ATOM reproduces the translocation of a substance in the intestinal lumen using a partial differential equation with variable dispersion and convection terms to describe natural flow and micromixing within the intestine under not only fasted but also fed conditions. In comparison with ATOM, it was suggested that a conventional absorption model, advanced compartmental absorption and transit model, tends to underestimate micromixing in the upper intestine, and it is difficult to adequately describe movements under the fasted and fed conditions. ATOM explains the observed nonlinear absorption of midazolam successfully, with a minimal number of scaling factors. Furthermore, ATOM considers the apical and basolateral membrane permeabilities of enterocytes sep. and assumes compartmentation of the lamina propria, including blood vessels, to consider intestinal blood flow appropriately. ATOM estimates changes in the intestinal availability caused by drug interaction associated with inhibition of CYP3A and P-glycoprotein in the intestine. Addnl., ATOM can estimate the drug absorption in the fed state considering delayed intestinal drug flow. Therefore, ATOM is a useful tool for the anal. of local pharmacokinetics in the gastrointestinal tract, especially for the estimation of nonlinear drug absorption, which may involve various interactions with intestinal contents or other drugs.

Drug Metabolism & Disposition 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

Yi, Hanxi published the artcileEvaluation of a modified flow-through method for predictive dissolution and in vitro/in vivo correlations of immediate release and extended release formulations, Category: pyridine-derivatives, the main research area is dissolution modified flow predictive method immediate extended release formulation.

The present study evaluated the ability of a modified flow-through method for predicting in vivo performance of immediate release (IR) and extended release (ER) formulations. In vitro dissolution of two model drugs, paracetamol IR tablets and felodipine ER tablets, was investigated under tuned conditions using the modified flow-through method and compared with the compendial quality control (QC) basket method. The in vivo absorption properties of paracetamol IR tablets and felodipine ER tablets were investigated in healthy volunteers. In vitro-in vivo correlation (IVIVC) anal. was performed based on the obtained in vitro and in vivo data. Our results demonstrated that the compendial QC method was not able to reflect in vivo actual absorption, while satisfactory discriminatory power and comparable in vitro dissolution/in vivo absorption were achieved for both paracetamol IR tablets and felodipine ER tablets by the modified flow-through method. This study indicated that the modified flow-through method is a potential tool to reflect in vivo performance of the IR and ER formulations.

Journal of Nanomaterials 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, Category: pyridine-derivatives.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Abuhassan, Qamar published the artcileStructured solubility behaviour in bioequivalent fasted simulated intestinal fluids, Quality Control of 72509-76-3, the main research area is bioequivalent fasted simulated intestinal fluid solubility.

Drug solubility in intestinal fluid is a key parameter controlling absorption after the administration of a solid oral dosage form. To measure solubility in vitro simulated intestinal fluids have been developed, but there are multiple recipes and the optimum is unknown. This situation creates difficulties during drug discovery and development research. A recent study characterised sampled fasted intestinal fluids using a multidimensional approach to derive nine bioequivalent fasted intestinal media that covered over 90% of the compositional variability. These media have been applied in this study to examine the equilibrium solubility of twenty one exemplar drugs (naproxen, indomethacin, phenytoin, zafirlukast, piroxicam, ibuprofen, mefenamic acid, furosemide, aprepitant, carvedilol, tadalafil, dipyridamole, posaconazole, atazanavir, fenofibrate, felodipine, griseofulvin, probucol, paracetamol, acyclovir and carbamazepine) to determine if consistent solubility behavior was present. The bioequivalent media provide in the majority of cases structured solubility behavior that is consistent with physicochem. properties and previous solubility studies. For the acidic drugs (pKa < 6.3) solubility is controlled by media pH, the profile is identical and consistent and the lowest and highest pH media identify the lowest and highest solubility in over 70% of cases. For weakly acidic (pKa > 8), basic and neutral drugs solubility is controlled by a combination of media pH and total amphiphile concentration (TAC), a consistent solubility behavior is evident but with variation related to individual drug interactions within the media. The lowest and highest pH x TAC media identify the lowest and highest solubility in over 78% of cases. A subset of the latter category consisting of neutral and drugs non-ionised in the media pH range have been identified with a very narrow solubility range, indicating that the impact of the simulated intestinal media on their solubility is minimal. Two drugs probucol and atazanavir exhibit unusual behavior. The study indicates that the use of two appropriate bioequivalent fasted intestinal media from the nine will identify in vitro the maximum and min. solubility boundaries for drugs and due to the media derivation this is probably applicable in vivo. These media could be applied during discovery and development activities to provide a solubility range, which would assist placement of the drug within the BCS/DCS and rationalise drug and formulation decisions.

European Journal of Pharmaceutics and Biopharmaceutics 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, Quality Control of 72509-76-3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Krollik, Katharina published the artcileThe effect of buffer species on biorelevant dissolution and precipitation assays – Comparison of phosphate and bicarbonate buffer, SDS of cas: 72509-76-3, the main research area is carbamazepine probenecid griseofulvin phosphate bicarbonate buffer; Bicarbonate buffer; Biorelevant media; Dissolution; Precipitation; Solubility testing.

Biorelevant solubility and dissolution testing is an important tool during pharmaceutical development, however, solubility experiments performed using biorelevant media often do not properly match the solubility data observed in human intestinal fluids. Even though the bicarbonate buffer is the predominant buffer system in the small intestine, in vitro assays are commonly performed using non-volatile buffer systems like phosphate and maleate. In the current study, bicarbonate- and phosphate-buffered biorelevant media were applied to solubility, dissolution, and precipitation testing for a broad range of model compounds It was found that the medium affects primarily the dissolution kinetics. However, with the knowledge of the unique buffering properties of bicarbonate buffer in the diffusion layer, it was not always possible to predict the effect of buffer species on solubility and dissolution when changing from phosphate to bicarbonate buffer. This once again highlights the special role of bicarbonate buffer for simulating the conditions in the human intestinal fluids. Moreover, it is necessary to further investigate the factors which may cause the differences in solubility and dissolution behavior when using phosphate- vs. bicarbonate-buffered biorelevant media.

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, SDS of cas: 72509-76-3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Guo, Changchuan published the artcileTargeted and nontargeted screening and identification of 50 antihypertensive adulterants in dietary supplements and herbal medicines using quadrupole-orbitrap high resolution mass spectrometry with compound database, Category: pyridine-derivatives, the main research area is antihypertensive dietary supplement adulterant screening spectrometry; adulteration; antihypertensives; identification; mass spectrometry; orbitrap; traditional Chinese medicine.

In the present work, a novel database of drug compounds and a rapid screening method based on ultra-high performance liquid chromatog. coupled to high resolution orbitrap mass spectrometry were developed and applied in the screening and identification of targeted and nontargeted antihypertensive adulterants in dietary supplements and herbal medicines. The established screening database includes retention time, exact mass, fragments, isotopic pattern, and MS2 spectra library of the target compounds and thus provides automated search and identification of the targets with a single injection. The nontargeted compounds in the samples are identified through the full MS scan and MS2 data by using the Chemspider database and the data anal. in XCalibur, MassFrontier and TraceFinder software. In addition, this method possesses excellent quant. capacity. The novel approach was applied to 65 batches of samples that are claimed as “”all-natural”” products having the antihypertensive function, among which nine batches were found to be pos. Multiple targeted and nontargeted antihypertensive adulterants were detected at levels ranging from 2.8 to 27.9 mg/g. The novel database and screening method demonstrated herein will be promising and powerful tools for rapid screening of antihypertensive adulterants in dietary supplements and herbal medicines.

Journal of Separation Science published new progress about Adulterants. 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, Category: pyridine-derivatives.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Zadymova, N. M. published the artcileNanoemulsions Containing Incorporated Lipophilic Drug, Felodipine, and Microheterogeneous Adhesive Polymer Matrices Based on These Nanoemulsions, SDS of cas: 72509-76-3, the main research area is lipophilic felodipine microheterogeneous adhesive polymer matrix nanoemulsion.

Oil-in-water nanoemulsions (NEs) have been obtained with a simple composition, in which a lipophilic non-micelle-forming nonionic surfactant (Tween 85) serves as both a dispersed phase and a stabilizer. The NEs remain in a metastable state for a long time (several months) and have a highly developed sp. surface area (Ssp ≃ 63 m2/g) and a high solubilization capacity with respect to a lipophilic hypotensive drug, felodipine (FD). Nanosized droplets (dav ≃ 95 nm) of the NEs efficiently transport FD in an aqueous medium. The oil-in-water NEs of Tween 85 with incorporated FD and a solution of a polymer adhesive (a blend of polyisobutylenes having different mol. weights and polybutene) in heptane have been used to obtain oil1/water/oil2 double emulsions, which are used as premixes for polymer microheterogeneous matrixes. Obtained polymer films are characterized by a good adhesion to skin, the absence of FD crystallization, and a constant rate of its release for several hours.

Colloid Journal published new progress about Aggregation. 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

Buchwald, Peter published the artcileSoft drugs: design principles, success stories, and future perspectives, Quality Control of 72509-76-3, the main research area is Soft drug design success story future perspective; Antedrug; drug metabolism; esterases; methylphenidate; prodrug; sofpironium; therapeutic index; toxic metabolite.

In the present study, the SD concept is part of the more general recognition that drug design needs to fully integrate metabolic con-siderations from the very beginning as metabolites contribute significantly to the overall activity and toxicity profile of the original drug and focus not on improving activity alone, but on improving the activity/toxicity ratio. This is usually characterized by the therapeutic index, typically defined as the ratio between the half-maximal toxic and effec-tive doses: TI = TD50/ED50. These ideas are the main underlying principles of retrometabolic drug design, which incorporates both SD and chem. delivery system (CDS) design. For most drugs, several metabolites are formed following administration, and they can contribute significantly not just to the overall activity, but also to toxicity and side effects. This can lead to complex time-profiles as illustrated in Figure 1(a), which shows the case of a hypothetical drug D that is present together with its active, toxic, and inactive metabolites. In light of these, the SD approach, which provides general drug design strategies, has particular potential. Because it often starts from a known active structure and focuses on designing safer drugs by decreasing side effects and toxicity, the likelihood of success is increased, especially considering the perspective highlighted by Sir James Black: the most fruitful basis for the discovery of a new drug is to start with an old drug.

Expert Opinion on Drug Metabolism & Toxicology published new progress about Anesthetics. 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

Dzodic, Predrag published the artcileA reliable chromatographic method for the simultaneous determination of ciprofloxacin and moxifloxacin in human serum, Synthetic Route of 72509-76-3, the main research area is serum ciprofloxacin moxifloxacin high performance liquid chromatog.

Purpose: To develop and validate a simple chromatog. method for the anal. of ciprofloxacin and moxifloxacin in human serum. Methods: After protein precipitation had been performed, high performance liquid chromatog. (HPLC) with UV detection was utilized for the anal. of ciprofloxacin and moxifloxacin in human serum. Anal. column Zorbax SB-C18 (150 mm x 4.6 mm i.d., particle size 3.5μm) was used as a stationary phase. Chromatog. separation was realized with the mobile phase 0.1% trifluoroacetic acid in water for chromatog. – methanol (66:34, volume/volume), at the flow rate of 1 mL/min, temperature of 35°C and detection at 280 nm. The method validation was performed according to the guidelines of the European Medicines Agency (EMA). Results: The chromatog. run time was about 12 min and no interference was observed For ciprofloxacin, the method was linear over a concentration range of 0.5-50μg/mL, with a correlation coefficient of 0.9874. For moxifloxacin, the method was linear over a concentration range of 0.5-50μg/mL, with a correlation coefficient of 0.9946. Since relative standard deviation (RSD) and relative recovery values were within acceptable limits according to EMA guidelines, good intra-day precision, inter-day precision, as well as the accuracy of the method, were observed Conclusion: A simple and reliable HPLC-UV method has been developed and validated for the simultaneous determination of ciprofloxacin and moxifloxacin in human serum. The method can be applied for therapeutic drug monitoring but also and pharmacokinetic studies of ciprofloxacin and moxifloxacin.

Tropical Journal of Pharmaceutical Research published new progress about Blood serum. 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

Wang, Dongdong published the artcileCyclosporin population pharmacokinetics in pediatric refractory nephrotic syndrome based on real-world studies: effects of body weight and spirolactone administration, Recommanded Product: 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is refractory nephrotic syndrome cyclosporin spirolactone body weight pharmacokinetics pediatrics; cyclosporin; pediatric refractory nephrotic syndrome; population pharmacokinetics; real-world study; spirolactone; weight.

Different models of population pharmacokinetics (PPK) of cyclosporin have been established in various populations. However, the cyclosporin PPK model in patients with pediatric refractory nephrotic syndrome (PRNS) has yet to be constructed. The present study aimed to establish the cyclosporin PPK model in PRNS, and to identify factors that may account for any variability. Chinese patients with PRNS treated with cyclosporin between June 2014 and June 2018 at the Children’s Hospital of Fudan University (Shanghai, China) were retrospectively analyzed. The impact of demog. features, laboratory parameters and concomitant medications was evaluated. A total of 18 PRNS patients from real-world studies were analyzed by non-linear mixed-effects modeling. A one-compartment model with first-order absorption and elimination was selected as the appropriate model in PRNS. Body weight (WT) and spirolactone intake were included as significant covariates for the apparent oral clearance (CL/F), and the WT was revealed to significantly influence the apparent volume of distribution (V/F). The final covariate models were as follows: CL/F = 80.7 × (WT/70)0.75 × (1-0.265 × θspirolactone), and V/F = 2,030 × (WT/70), where θspirolactoneis the coefficient of spirolactone. The inter-individual variability in CL/F and V/F was 44.6 and 53.1%, resp. In conclusion, in the present study, a cyclosporin PPK model for patients with PRNS was successfully constructed, and the presence of a clin. significant interaction between spirolactone and cyclosporin in PRNS patients was determined based on real-world studies, indicating that concomitant medication with spirolactone was able to reduce cyclosporin clearance in the patients with PRNS.

Experimental and Therapeutic Medicine published new progress about Body weight. 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

Salunkhe, N. H. published the artcileValidated RP-HPLC method for quantification of felodipine in rabbit plasma: Application in a bioequivalence study, Name: 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is RP HPLC method felodipine rabbit plasma; Felodipine; La nimodipine; Nimodipine; Plasma de lapin; RP-HPLC; Rabbit plasma; Validation.

The aim of present study was to develop a simple, rapid, selective, sensitive and robust reverse phase high performance liquid chromatog. method for quantification of felodipine in rabbit plasma at the wavelength of 360 nm. Protein was precipitated from rabbit plasma sample by addition of acetonitrile as a vehicle. An isocratic elution of samples was performed on capcell pak C8 DD S5 column (4.6 mm × 250 mm particle size 5μm) column with mobile phase consisting 5 mM Phosphate Buffer (pH 4.8 adjusted with dilute ortho-phosphoric acid solution): acetonitrile (25:75:volume/volume) delivered at flow rate 1.0 mL min-1. A good linear response was achieved over the range of 0.25-20.00 g mL-1. LODs and LOQs for felodipine were found to be 0.055 and 0.201μg mL-1, resp. The method was quant. evaluated in terms of linearity, precision, accuracy (recovery), selectivity robustness and stability study as per standard guidelines. The validated RP-HPLC method was successfully applied for the bioavailability studies of felodipine. The pharmacokinetic parameters were calculated for all the investigated drugs in rabbit after single-dose administrations of pure drug and formulation of felodipine. Finally, the obtained results for the application of the proposed RP-HPLC method proved its efficiency to be applied to the therapeutic drug monitoring (TDM) and bioequivalence (BE) studies. Thus, developed method is simple, convenient and suitable for the anal. of felodipine in bulk and pharmaceutical formulations.

Annales Pharmaceutiques Francaises published new progress about Blood plasma. 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, Name: 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem