Category: 72509-76-3

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

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

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

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

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

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

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

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

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

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

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

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

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

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

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

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Ge, Kai published the artcileNovel Computational Approach by Combining Machine Learning with Molecular Thermodynamics for Predicting Drug Solubility in Solvents, Formula: C18H19Cl2NO4, the main research area is antipyrine benzamide doxofylline gefitinib thermodn machine learning.

In this work, a novel strategy that combined mol. thermodn. and machine learning was proposed to accurately predict the solubility of drugs in various solvents. The strategy was based on 16 mol. descriptors representing drug-drug interactions and drug-solvent interactions including phys. parameters, pure perturbed-chain statistical associating fluid theory (PC-SAFT) parameters of drugs and solvents, and mixing rules. These mol. descriptors were inputted into five machine learning algorithms [multiple linear regression (MLR), artificial neural network (ANN), random forest (RF), extremely randomized trees (ET), and support vector machine (SVM)] to train the predictive model. A single-hidden-layer neural network was finally determined as the predictive model for predicting the solubility of drugs in various solvents. The drug solubility in the generalization evaluation set has also been successfully predicted, which indicates the good prediction performance of the model. Three directions for improving the model were summarized as adding mol. descriptors of drug-solvent interactions in the water system and drug-drug interactions in the organic solvent system and expanding the dataset to adequately obtain the features of multiple drugs. These findings show that the proposed model has the capability of solubility prediction, which is expected to provide important information for drug development and drug solvent screening.

Industrial & Engineering Chemistry Research published new progress about Drug discovery. 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, Formula: C18H19Cl2NO4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Achim, Marcela published the artcilePreparation and in vitro evaluation of felodipineloaded poly(ε-caprolactone) microspheres: quality by design approach, Category: pyridine-derivatives, the main research area is felodipine polycaprolactone microsphere polydispersity index drug development.

Felodipine was encapsulated into poly(ε-caprolactone) microspheres by the emulsion solvent evaporation method by employing the Quality by Design (QbD) strategy. Based on a risk anal., the influence of 4 critical process parameters (type of stirrer, stirring rate, shape of mixing vessel, aqueous phase volume) on the critical quality attributes of the microspheres (size, polydispersity, entrapment efficiency (EE)), was evaluated by a full factorial exptl. design. The microspheres’ morphol. and felodipine in vitro release were also studied. The particles’ size ranged between 39.8 and 302.5μm, and the polydispersity index varied from 0.279 to 0.517. Felodipine EE was above 93.59%. SEM (SEM) anal. revealed spherical particles, with imperfections and micropores on the surface. The microspheres exhibited an extended release of felodipine over a period of 12 h. In conclusion, the QbD approach helped understand the process parameters and their impact on the quality profile in the development of felodipine-loaded microspheres.

Farmacia (Bucharest, Romania) published new progress about Drug discovery. 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

Solomon, Samuel published the artcileInsights into the ameliorating ability of mesoporous silica in modulating drug release in ternary amorphous solid dispersion prepared by hot melt extrusion, HPLC of Formula: 72509-76-3, the main research area is mesoporous silica drug release solid dispersion hotmelt extrusion; Felodipine; Hotmelt Extrusion; Soluplus; Solvent less; Ternary dispersions.

In this work, the application of various mesoporous silica grades in the preparation of stabilized ternary amorphous solid dispersions of Felodipine using hot melt extrusion was explored. We have demonstrated the effectiveness of mesoporous silica in these dispersions without the need for any organic solvents i.e., no pre-loading or immersion steps required. The phys. and chem. properties, release profiles of the prepared formulations and the surface concentrations of the various mol. species were investigated in detail. Formulations containing 25 wt% and 50 wt% of Felodipine demonstrated enhanced stability and solubility of the drug substance compared to its crystalline counterpart. Based on the Higuchi model, ternary formulations exhibited a 2-step or 3-step release pattern which can be ascribed to the release of drug mols. from the organic polymer matrix and the external silica surface, followed by a release from the silica pore structure. According to the Korsmeyer-Peppas model, the release rate and release mechanism are governed by a complex quasi-Fickian release mechanism, in which multiple release mechanisms are occurring concurrently and consequently. Stability studies indicated that after 6 mo storage of all formulation at 30% RH and 20°C, Felodipine in all formulations remained stable in its amorphous state except for the formulation comprised of 40 wt% Syloid AL-1FP with a 50 wt% drug load.

European Journal of Pharmaceutics and Biopharmaceutics published new progress about Drug stability. 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

Sun, Lin published the artcileFelodipine-associated gingival overgrowth in a type 2 diabetic patient: a case report and literature review, Category: pyridine-derivatives, the main research area is type 2 diabetes gingival overgrowth felodipine; calcium channel blocker; drug-induced gingival overgrowth; felodipine.

Gingival overgrowth (GO) includes gingival enlargement and hyperplasia and may be induced by certain drugs, including calcium channel blockers (CCBs), particularly first-generation CCBs. However, to date, only few cases of GO induced by second- or third-generation CCBs have been reported. The present study reports on a case of a 48-yr-old diabetic male who was admitted to the First Hospital of Jilin University (Changchun, China) due to poor blood glucose control. This patient was diagnosed with GO. Review of the patient’s medical history revealed diagnoses of type 2 diabetes and hypertension, as well as the use of felodipine, a second-generation CCB, to control hypertension. The hypertensive drugs were replaced and the new drugs helped the patient control his blood glucose levels. Addnl., the patient was instructed on methods he could use to improve his oral hygiene, including rinsing of the teeth following each meal and increasing the frequency of tooth brushing per day. After 3 mo, the clin. symptoms of GO were relieved. The relevant literature was also reviewed to gain an improved understanding of the correlation between GO and CCBs, as well as diabetes and poor oral hygiene.

Experimental and Therapeutic Medicine published new progress about Adrenal gland. 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

Fu, Edouard L. published the artcileComparative Effectiveness of Renin-Angiotensin System Inhibitors and Calcium Channel Blockers in Individuals With Advanced CKD: A Nationwide Observational Cohort Study, Synthetic Route of 72509-76-3, the main research area is RAS inhibitor calcium channel blocker chronic kidney disease; Angiotensin-converting enzyme inhibitors (ACEi); CKD progression; advanced CKD; amlodipine; angiotensin receptor blockers (ARB); antihypertensive; calcium channel blockers (CCB); chronic kidney disease (CKD); comparative effectiveness; enalapril; end-stage kidney disease (ESKD); major adverse cardiovascular events (MACE); mortality; renoprotection.

It is unknown whether initiating renin-angiotensin system (RAS) inhibitor therapy in patients with advanced chronic kidney disease (CKD) is superior to alternative antihypertensive agents such as calcium channel blockers (CCBs). We compared the risks for kidney replacement therapy (KRT), mortality, and major adverse cardiovascular events (MACE) in patients with advanced CKD in routine nephrol. practice who were initiating either RAS inhibitor or CCB therapy. Observational study in the Swedish Renal Registry, 2007 to 2017.2,458 new users of RAS inhibitors and 2,345 CCB users with estimated glomerular filtration rates < 30 mL/min/1.73 m2 (CKD G4-G5 without KRT) who were being followed up by a nephrologist. As a pos. control cohort, new users of the same drugs with CKD G3 (estimated glomerular filtration rate, 30-60 mL/min/1.73 m2) were evaluated. RAS inhibitor vs. CCB therapy initiation. Initiation of KRT (maintenance dialysis or transplantation), all-cause mortality, and MACE (composite of cardiovascular death, myocardial infarction, or stroke). HRs with 95% CIs were estimated using propensity score-weighted Cox proportional hazards regression adjusting for demog., clin., and laboratory covariates. Median age was 74 years, 38% were women, and median follow-up was 4.1 years. After propensity score weighting, there was significantly lower risk for KRT after new use of RAS inhibitors compared with new use of CCBs (adjusted HR, 0.79 [95% CI, 0.69-0.89]) but similar risks for mortality (adjusted HR, 0.97 [95% CI, 0.88-1.07]) and MACE (adjusted HR, 1.00 [95% CI, 0.88-1.15]). Results were consistent across subgroups and in as-treated analyses. The pos. control cohort of patients with CKD G3 showed similar KRT risk reduction (adjusted HR, 0.67 [95% CI, 0.56-0.80]) with RAS inhibitor therapy compared with CCBs. Potential confounding by indication. Our findings provide evidence from real-world clin. practice that initiation of RAS inhibitor therapy compared with CCBs may confer kidney benefits among patients with advanced CKD, with similar cardiovascular protection. American Journal of Kidney Diseases published new progress about Aging, animal. 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

El Sayed, Mira published the artcileImpact of Simulated Intestinal Fluids on Dissolution, Solution Chemistry, and Membrane Transport of Amorphous Multidrug Formulations, Application In Synthesis of 72509-76-3, the main research area is multidrug formulation dissolution solubility membrane transport simulated intestinal fluid; FaSSIF; amorphous; fixed dose combination; flux; membrane transport; multidrug formulations; solubility; supersaturation.

The solution behavior and membrane transport of multidrug formulations were herein investigated in a biorelevant medium simulating fasted conditions. Amorphous multidrug formulations were prepared by the solvent evaporation method. Combinations of atazanavir (ATV) and ritonavir (RTV) and felodipine (FDN) and indapamide (IPM) were prepared and stabilized by a polymer for studying their dissolution (under non-sink conditions) and membrane transport in fasted state simulated intestinal fluid (FaSSIF). The micellar solubilization by FaSSIF enhanced the amorphous solubility of the drugs to different extents. Similar to buffer, the maximum achievable concentration of drugs in combination was reduced in FaSSIF, but the extent of reduction was affected by the degree of FaSSIF solubilization. Dissolution studies of ATV and IPM revealed that the amorphous solubility of these two drugs was not affected by FaSSIF solubilization. In contrast, RTV was significantly affected by FaSSIF solubilization with a 30% reduction in the maximum achievable concentration upon combination to ATV, compared to 50% reduction in buffer. This pos. deviation by FaSSIF solubilization was not reflected in the mass transport-time profiles. Interestingly, FDN concentrations remain constant until the amount of IPM added was over 1000 μg/mL. No decrease in the membrane transport of FDN was observed for a 1:1 M ratio of FDN-IPM combination. This study demonstrates the importance of studying amorphous multidrug formulations under physiol. relevant conditions to obtain insights into the performance of these formulations after oral administration.

Molecular Pharmaceutics 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, Application In Synthesis of 72509-76-3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem