Category: pyridine-derivatives

Ma, Xiangyu published the artcileInfluence of mechanical and thermal energy on nifedipine amorphous solid dispersions prepared by hot melt extrusion: Preparation and physical stability, Application In Synthesis of 21829-25-4, the main research area is nifedipine amorphous solid dispersion extrusion stability; Amorphous solid dispersion; Homogeneity; Hot melt extrusion; Physical stability; Specific mechanical energy; Thermal energy.

Hot melt extrusion (HME) has been used to prepare solid dispersions, especially molecularly dispersed amorphous solid dispersions (ASDs) for solubility enhancement purposes. The energy generated by the extruder in the form of mech. and thermal output enables the dispersion and dissolution of crystalline drugs in polymeric carriers. However, the impact of this thermal and mech. energy on ASD systems remains unclear. We selected a model ASD system containing nifedipine (NIF) and polyvinylpyrrolidone vinyl acetate (PVP/VA 64) to investigate how different types of energy input affect the preparation and phys. stability of ASDs. Formulations were prepared using a Leistritz Nano-16 extruder, and we varied the screw design, barrel temperature, screw speed, and feed rate to control the mech. and thermal energy input. Specific mech. energy (SME) was calculated to quantitate the mech. energy input, and the thermal energy was estimated using barrel temperature We find that both mech. and thermal energy inputs affect the conversion of crystalline NIF into an amorphous form, and they also affect the level of mixing and the degree of homogeneity in NIF ASDs. However, for small size extruders (e.g., Leistritz Nano-16), thermal energy is more efficient than mech. energy in preparing NIF ASDs that have better stability.

International Journal of Pharmaceutics (Amsterdam, Netherlands) published new progress about Amorphous materials. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Application In Synthesis of 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Zhou, Deliang published the artcileAssessing physical stability risk using the amorphous classification system (ACS) based on simple thermal analysis, Synthetic Route of 72509-76-3, the main research area is phys stability risk amorphous classification thermal analysis; amorphous classification system (ACS); amorphous solid dispersions (ASD); configurational entropy; crystallization; differential scanning calorimetry (DSC); molecular mobility; physical stability; risk assessment.

The purpose of this study is to develop a classification system utilizing milligram amounts of the compound for phys. stability ranking of amorphous pharmaceuticals, which can be used as an early risk assessment tool for amorphous solid dispersion formulations. Simple thermal anal. utilizing a differential scanning calorimeter is used to characterize amorphous pharmaceuticals with respect to their mol. mobility and configurational entropy. Mol. mobility and configurational entropy are considered as two critical factors in determining the phys. stability of amorphous phases. Theor. arguments and numerical simulations suggest that the fragility strength parameter is a good indicator of the mol. mobility below Tg, and the heat capacity change at Tg is a good indicator of the configurational entropy. Using these two indicators, 40 structurally diverse pharmaceuticals with known phys. stability were analyzed. Four classes of compounds are defined with class I being the most stable and class IV the least stable. The proposed amorphous classification system and methodol. for estimating mol. mobility and configurational entropy provides an easily accessible framework to conduct early risk assessments related to phys. stability challenges in developing amorphous formulations.

Molecular Pharmaceutics published new progress about Amorphous materials. 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

Sarpal, Kanika published the artcileAmorphous Solid Dispersions of Felodipine and Nifedipine with Soluplus: Drug-Polymer Miscibility and Intermolecular Interactions, Category: pyridine-derivatives, the main research area is felodipine nifedipine soluplus miscibility polymer; Amorphous solid dispersions; Hydrogen bonding; Phase heterogeneity; Solid-state nuclear magnetic resonance spectroscopy; Thermodynamic miscibility.

The objective of this study was to investigate thermodn. and kinetic miscibility for two structurally similar model compounds nifedipine (NIF) and felodipine (FEL) when formulated as amorphous solid dispersions (ASDs) with an amphiphilic polymer Soluplus. Thermodn. miscibility was studied via m.p. depression approach for the two systems. The Flory Huggins theory was used to calculate the interaction parameter and generate the phase diagrams. It was shown that NIF was more miscible in Soluplus than FEL. The nature of drug-polymer interactions was studied by fourier transform infra-red spectroscopy (FTIR) and solid-state NMR spectroscopy (ssNMR). The data from spectroscopic analyses showed that both the drugs interacted with Soluplus through hydrogen bonding interactions. Furthermore, 13C ssNMR data was used to get quant. estimate of the extent of hydrogen bonding for ASDs samples. Proton relaxation measurements were carried out on ASDs in order to evaluate phase heterogeneity on two different length scales of mixing. The data suggested that better phase homogeneity in NIF:SOL systems especially for lower Soluplus content ASDs on smaller domains. This could be explained by understanding the extent of hydrogen bonding interactions for these two systems. This study highlights the need to consider thermodn. and kinetic mixing, when formulating ASDs with the goal of understanding phase mixing between drug and polymer.

Journal of Pharmaceutical Sciences (Philadelphia, PA, United States) published new progress about Amorphous materials. 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

Sarpal, Kanika published the artcileAmorphous Solid Dispersions of Felodipine and Nifedipine with Soluplus: Drug-Polymer Miscibility and Intermolecular Interactions, Application In Synthesis of 21829-25-4, the main research area is felodipine nifedipine soluplus miscibility polymer; Amorphous solid dispersions; Hydrogen bonding; Phase heterogeneity; Solid-state nuclear magnetic resonance spectroscopy; Thermodynamic miscibility.

The objective of this study was to investigate thermodn. and kinetic miscibility for two structurally similar model compounds nifedipine (NIF) and felodipine (FEL) when formulated as amorphous solid dispersions (ASDs) with an amphiphilic polymer Soluplus. Thermodn. miscibility was studied via m.p. depression approach for the two systems. The Flory Huggins theory was used to calculate the interaction parameter and generate the phase diagrams. It was shown that NIF was more miscible in Soluplus than FEL. The nature of drug-polymer interactions was studied by fourier transform infra-red spectroscopy (FTIR) and solid-state NMR spectroscopy (ssNMR). The data from spectroscopic analyses showed that both the drugs interacted with Soluplus through hydrogen bonding interactions. Furthermore, 13C ssNMR data was used to get quant. estimate of the extent of hydrogen bonding for ASDs samples. Proton relaxation measurements were carried out on ASDs in order to evaluate phase heterogeneity on two different length scales of mixing. The data suggested that better phase homogeneity in NIF:SOL systems especially for lower Soluplus content ASDs on smaller domains. This could be explained by understanding the extent of hydrogen bonding interactions for these two systems. This study highlights the need to consider thermodn. and kinetic mixing, when formulating ASDs with the goal of understanding phase mixing between drug and polymer.

Journal of Pharmaceutical Sciences (Philadelphia, PA, United States) published new progress about Amorphous materials. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Application In Synthesis of 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Sahoo, Anasuya published the artcileStabilization of Amorphous Drugs by Polymers: The Role of Overlap Concentration (C*), Safety of 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is amorphous solid dispersion overlap concentration melt quenching crystallization; amorphous solid dispersions (ASD); crystallization; enthalpy of fusion; melt quenching; overlap concentration (C*).

Amorphous solid dispersions (ASDs), in which polymers are admixed with a drug, retard or inhibit crystallization of the drug, increasing the drug’s apparent solubility and oral bioavailability. To date, there are no guidelines regarding how much polymer should be added to stabilize the amorphous form of the drug. We hypothesized that only drug that is not within a “”sphere of influence”” of a polymer chain is able to nucleate and form crystals and that the degree of crystallization should depend primarily on the ratio C/C*, where C is the polymer concentration and C* is the overlap concentration We tested this hypothesis by quenching dispersions of polyvinylpyrrolidone (PVP) dissolved in molten felodipine (FEL) or indomethacin (IMC) at four mol. weights of PVP. For each mol. weight of PVP, C* in the drug (as solvent) was determined by dynamic light scattering and intrinsic viscosity. The enthalpy of fusion (ΔHf), determined by DSC, was used to measure the fraction of drug that crystallized in an ASD. It was found, roughly, that ΔHf/ΔHf,C=0 = f(C/C*) and that no crystallization occurred when C > C*. XRD also showed that crystallization was completely inhibited up to ~Tg + 75°C when the polymer concentration was above C*. Our results suggest that stabilization of amorphous drugs can be achieved by incorporating a polymer just above C*, which is much lower than polymer concentrations customarily used in ASDs. This work reveals the importance of C* in selecting polymer concentrations when formulating drugs as ASDs.

Molecular Pharmaceutics published new progress about Amorphous structure. 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

Shi, Nian-Qiu published the artcileThe Influence of Cellulosic Polymers Variables on Dissolution/Solubility of Amorphous Felodipine and Crystallization Inhibition from a Supersaturated State, Related Products of pyridine-derivatives, the main research area is dissolution solubility amorphous felodipine crystallization cellulose; amorphous drug; cellulosic polymers; crystallization inhibition; dissolution/solubility enhancement; supersaturated state.

The collective impact of cellulosic polymers on the dissolution, solubility, and crystallization inhibition of amorphous active pharmaceutical ingredients (APIs) is still far from being adequately understood. The goal of this research was to explore the influence of cellulosic polymers and incubation conditions on enhancement of solubility and dissolution of amorphous felodipine, while inhibiting crystallization of the drug from a supersaturated state. Variables, including cellulosic polymer type, amount, ionic strength, and viscosity, were evaluated for effects on API dissolution/solubility and crystallization processes. Water-soluble cellulosic polymers, including HPMC E15, HPMC E5, HPMC K100-LV, L-HPC, and MC, were studied. All cellulosic polymers could extend API dissolution and solubility to various extents by delaying crystallization and prolonging supersaturation duration, with their effectiveness ranked from greatest to least as HPMC E15 > HPMC E5 > HPMC K100-LV > L-HPC > MC. Decreased polymer amount, lower ionic strength, or higher polymer viscosity tended to decrease dissolution/solubility and promote crystal growth to accelerate crystallization HPMC E15 achieved greatest extended API dissolution and maintenance of supersaturation from a supersaturated state; this polymer thus had the greatest potential for maintaining sustainable API absorption within biol. relevant time frames.

AAPS PharmSciTech published new progress about Amorphous structure. 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

Baxevanis, Fotios published the artcileInvestigation of drug partition kinetics to fat in simulated fed state gastric conditions based on drug properties, Recommanded Product: 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is simulated gastric fluid fat drug partition kinetics; Drug partition; Fed state; Food effect; Partial least squares regression; Physicochemical properties.

The presence of fat in the gastric environment can affect the pharmacokinetic behavior of drugs with mechanisms which have not been yet fully understood. The objective of the current study was to assess the drug partition to the lipid part of the fed gastric content under different emulsification conditions, using in vitro discriminating setups. The model drugs used in the study were selected on the basis of different physicochem. properties (lipophilicity, ionization, mol. weight and aqueous solubility) and different food effect observed in in vivo human studies. Fed State Simulated Gastric Fluid prepared with skimmed milk (FeSSGFsk) and anhydrous milk fat were used as surrogates for the aqueous and fat portions of the fed gastric environment resp. An optimized biphasic model was developed so as to predict the differences in partition rate constants to fat, for model drugs of a wide range of the properties mentioned above. The exptl. data and the use of statistical anal. revealed that mol. weight, mol. weight and log D pH5 interaction and neg. food effect act as neg. factors to the rate constants of fat partition, while absence of food effect and logD pH 5interaction with aqueous solubility affect the rate constants of partition to fat favorably.

European Journal of Pharmaceutical Sciences published new progress about Anionic surfactants. 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

Suriyapakorn, Bovornpat published the artcileComparison of potential drug-drug interactions with metabolic syndrome medications detected by two databases, Category: pyridine-derivatives, the main research area is atenolol bisoprolol enalapril imidapril antiplatelet antilipemic antihypertensive metabolic syndrome.

Drug-drug interactions (DDIs) are one of the most common drug-related problems. Recently, electronic databases have drug interaction tools to search for potential DDIs, for example, Micromedex and Drugs.com. However, Micromedex and Drugs.com have different abilities in detecting potential DDIs, and this might cause misinformation to occur between patients and health care providers. The aim of this study was to compare the ability of Micromedex and Drugs.com to detect potential DDIs with metabolic syndrome medications using the drug list from the U-central database, King Chulalongkorn Memorial Hospital in Apr. 2019. There were 90 available drugs for the treatment of the metabolic syndrome and its associated complications, but six were not found in the Micromedex and Drugs.com databases; therefore, only 84 items were used in the present study. There were 1,285 potential DDI pairs found by the two databases. Micromedex reported DDIs of 724 pairs, while, Drugs.com reported 1,122 pairs. For the severity of the potential DDI reports, the same severity occurred between the two databases of 481 pairs (37.43%) and a different severity for 804 pairs (62.57%). Drugs.com had a higher sensitivity to detect potential DDIs by approx. 1.5-fold, but Micromedex supplied more informative documentation for the severity classification. Therefore, pharmacists should use at least two databases to evaluate potential DDIs and determine the appropriate drug regimens for physician communications and patient consultations.

PLoS One published new progress about Antidiabetic agents. 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

Turkes, Cuneyt published the artcileAnti-diabetic Properties of Calcium Channel Blockers: Inhibition Effects on Aldose Reductase Enzyme Activity, Application In Synthesis of 21829-25-4, the main research area is cinnarizine calcium channel blocker antidiabetic agent aldose reductase; Aldose reductase; Calcium channel blockers; Inhibition; Purification.

Aldose reductase (AR) belongs to NADPH-dependent oxidoreductases and converts glucose to sorbitol in the polyol pathway. AR inhibition is essential to prevent diabetic complications. Here, AR was purified from sheep kidney using simple methods and determined the interactions between some calcium channel blockers and the enzyme. It was found that calcium channel blockers (cinnarizine, nilvadipine, amlodipine besylate, nifedipine, isradipine, and nitrendipine) exhibit potential inhibitor properties for sheep kidney AR with IC50 values in the range of 5.87-8.77μM and Ki constants in the range of 2.07 ± 0.72-5.62 ± 1.53μM. The calcium channel blockers showed different inhibition mechanisms. It was determined that all studied compounds showed competitive inhibition effect except for isradipine and nitrendipine. They showed non-competitive inhibition. Among these drugs, cinnarizine was found to be the most potent AR inhibitor (Ki: 2.07 ± 0.72μM). They may be useful in the treatment and/or prevention of diabetic complications.

Applied Biochemistry and Biotechnology published new progress about Antidiabetic agents. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Application In Synthesis of 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Seo, Mi Seon published the artcileEmpagliflozin dilates the rabbit aorta by activating PKG and voltage-dependent K+ channels, Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is empagliflozin antidiabetic agent vasodilatory; Aorta; Empagliflozin; Protein kinase G; Voltage-dependent K(+) (Kv) channel.

We investigated the vasodilatory effects of empagliflozin (a sodium-glucose co-transporter 2 inhibitor) and the underlying mechanisms using rabbit aorta. Empagliflozin induced vasodilation in a concentration-dependent manner independently of the endothelium. Likewise, pretreatment with the nitric oxide synthase inhibitor L-NAME or the SKca inhibitor apamin together with the IKca inhibitor TRAM-34 did not impact the vasodilatory effects of empagliflozin. Pretreatment with the adenylyl cyclase inhibitor SQ22536 or a guanylyl cyclase inhibitor ODQ or a protein kinase A (PKA) inhibitor KT5720 also did not alter the vasodilatory response of empagliflozin. However, the vasodilatory effects of empagliflozin were significantly reduced by pretreatment with the protein kinase G (PKG) inhibitor KT5823. Although application of the ATP-sensitive K+ (KATP) channel inhibitor glibenclamide, large-conductance Ca2+-activated K+ (BKCa) channel inhibitor paxilline, or inwardly rectifying K+ (Kir) channel inhibitor Ba2+ did not impact the vasodilatory effects of empagliflozin, pretreatment with the voltage-dependent K+ (Kv) channel inhibitor 4-AP reduced the vasodilatory effects of empagliflozin. Pretreatment with DPO-1 (Kv1.5 channel inhibitor), guangxitoxin (Kv2.1 channel inhibitor), or linopirdine (Kv7 channel inhibitor) had little effect on empagliflozin-induced vasodilation. Application of nifedipine (L-type Ca2+ channel inhibitor) or thapsigargin (sarco-endoplasmic reticulum Ca2+-ATPase pump inhibitor) did not impact empagliflozin-induced vasodilation. Therefore, empagliflozin induces vasodilation by activating PKG and Kv channels.

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

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem