Category: 72509-76-3

Iwasaki, Shinji published the artcileApplication of unbound liver-to-plasma concentration ratio to quantitative projection of cytochrome P450-mediated drug-drug interactions using physiologically based pharmacokinetic modelling approach, Application of 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is liver plasma cytochrome drug interaction PBPK modeling approach; Drug–drug interaction; K; human cryopreserved hepatocytes; physiologically based pharmacokinetic model.

1. This study evaluated the prediction accuracy of cytochrome P 450 (CYP)-mediated drug-drug interaction (DDI) using minimal physiol.-based pharmacokinetic (PBPK) modeling incorporating the hepatic accumulation factor of an inhibitor (i.e. unbound liver/unbound plasma concentration ratio [Kp,uu,liver]) based on 22 clin. DDI studies.2. Kp,uu,liver values were estimated using three methods: (1) ratio of cell-to-medium ratio in human cryopreserved hepatocytes (C/Mu) at 37°C to that on ice (Kp,uu,C/M), (2) multiplication of total liver/unbound plasma concentration ratio (Kp,u,liver) estimated from C/Mu at 37°C with unbound fraction in human liver homogenate (Kp,uu,cell) and (3) observed Kp,uu,liver in rats after i.v. infusion (Kp,uu,rat).3. PBPK model using each Kp,uu,liver projected the area under the curve (AUC) increase of substrates more accurately than the model assuming a Kp,uu,liver of 1 for the average fold error and root mean square error did. Particularly, the model with a Kp,uu,liver of 1 underestimated the AUC increase of triazolam following co-administration with CYP3A4 inhibitor itraconazole by five-fold, whereas the AUC increase projected using the model incorporating the Kp,uu,C/M, Kp,uu,cell, or Kp,uu,rat of itraconazole and hydroxyitraconazole was within approx. two-fold of the actual value.4.

Xenobiotica 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, 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

Carling, Carl-Johan published the artcileMilling of poorly soluble crystalline drug compounds to generate appropriate particle sizes for inhaled sustained drug delivery, Quality Control of 72509-76-3, the main research area is lung inhaled sustained drug delivery; particle size AZD4854 milling dissolution; Dissolution; Inhaled sustained drug delivery; Milling; Nebulization; Suspension; Ultrasound.

One of the simplest design concepts of inhaled sustained drug delivery to the lung is to utilize the slow dissolution of drug crystals with poor aqueous solubility An optimum dissolution rate, and thereby a delivery profile locally in the lung tissue, can be achieved in a reliable way by selecting a compound with an appropriate combination of solubility and particle size. It is in our experience relatively straightforward to manufacture monomodal particle size distributions of poorly soluble drug crystals in the mass median diameter range of either a few micrometers or a few hundred nanometers, but very challenging to manufacture a monomodal distribution in the range intermediate to these two. In this manuscript, we describe an investigation with the objective of generating desired particle sizes in the whole size range from a few micrometers to a few hundred nanometers for inhaled sustained drug delivery, by utilizing Adaptive Focused Acoustic (AFA) milling and planetary bead-milling. By combining the two different milling techniques it was possible to produce two to three distinctly different monomodal or almost monomodal particle size distributions in the desired particle size range of each of the model drug compounds in milligram scale. The dissolution kinetics of the different particle sizes of the model drugs were measured exptl. as well as predicted theor., showcasing that the dissolution kinetics can be characterized, predicted and significantly changed in a controlled way by modifying the particle size. For one of the model drugs, it was shown in an in vivo rat study that the inhaled sustained drug delivery profile in the lung tissue could be significantly changed by modifying the particle size of the drug.

International Journal of Pharmaceutics (Amsterdam, Netherlands) 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, Quality Control of 72509-76-3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Poulin, Patrick published the artcileApplication of the Tissue Composition-Based Model to Minipig for Predicting the Volume of Distribution at Steady State and Dermis-to-Plasma Partition Coefficients of Drugs Used in the Physiologically Based Pharmacokinetics Model in Dermatology, Computed Properties of 72509-76-3, the main research area is dermis partition drug pharmacokinetics model dermatol; IVIVE; PBPK modeling; discovery; in silico; pharmacokinetics; tissue composition; topical; transdermal.

The minipig continues to build a reputation as a viable alternative large animal model to predict humans in dermatol. and toxicol. studies. Therefore, it is essential to describe and predict the pharmacokinetics in that species to speed up the clin. candidate selection. Essential input parameters in whole-body physiol. based pharmacokinetic models are the tissue-to-plasma partition coefficients and the resulting volume of distribution at steady-state (Vss). Mechanistic in vitro- and in silico-based models used for predicting these parameters of tissue distribution of drugs refer to the tissue composition-based model (TCM). Robust TCMs were initially developed for some preclin. species (e.g., rat and dog) and human; however, there is currently no model available for the minipig. Therefore, the objective of this present study was to develop a TCM for the minipig and to estimate the corresponding tissue composition data. Drug partitioning into the tissues was predominantly governed by lipid and protein binding effects in addition to drug solubilization and pH gradient effects in the aqueous phase on both sides of the biol. membranes; however, some more complex tissue distribution processes such as drug binding to the collagen-laminin material in dermis and a restricted drug partitioning into membranes of tissues for compounds that are amphiphilic and contain sulfur atom(s) were also challenged. The model was validated by predicting Vss and the dermis-to-plasma partition coefficients (Kp-dermis) of 68 drugs. The prediction of Kp-dermis was extended to humans for comparison with the minipig. The results indicate that the extended TCM provided generally good agreements with observations in the minipig showing that it is also applicable to this preclin. species. In general, up to 86% and 100% of the predicted Vss values are resp. within 2-fold and 3-fold errors compared to the exptl. determined values, whereas these numbers are 78% and 94% for Kp-dermis when the anticipated outlier compounds are not included. Binding data to dermis are comparable between minipigs and humans. Overall, this study is a first step toward developing a mechanistic TCM for the minipig, with the aim of increasing the use of physiol. based pharmacokinetic models of drugs for that species in addition to rats, dogs, and humans because such models are used in preclin. and clin. transdermal studies.

Journal of Pharmaceutical Sciences (Philadelphia, PA, United States) 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, Computed Properties of 72509-76-3.

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

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