Tag: M.W=350-400

Sarpal, Kanika published the artcilePhase Behavior of Amorphous Solid Dispersions of Felodipine: Homogeneity and Drug-Polymer Interactions, HPLC of Formula: 72509-76-3, the main research area is polymer interaction felodipine formulation; amorphous solid dispersions; differential scanning calorimetry; felodipine; hydrogen bonding; phase behavior; solid-state nuclear magnetic resonance spectroscopy.

In the current investigation, the role of drug-polymer hydrogen bonding (H-bonding) with respect to the phase behavior of amorphous solid dispersions (ASDs) is studied in depth on a nanometer level. Melt-quenched dispersions of felodipine (FEL) with poly(vinylpyrrolidone), or PVP, poly(vinylpyrrolidone-co-vinylacetate), or PVP/VA, and poly(vinylacetate), or PVAc, were prepared at drug loadings of 50-90% weight/weight Modulated differential scanning calorimetry (MDSC) was used to detect microscopic homogeneity for each set of ASDs. A single composition dependent glass transition temperature (Tg) was observed over the entire composition range in MDSC data for each set of ASDs; however some samples within each set of ASDs showed a crystallization exotherm and corresponding melting endotherm in the first heating scan. Solid-state NMR spectroscopy (SSNMR) was further employed to understand phase homogeneity in these systems. The proton spin-lattice relaxation times in the laboratory and rotating frame (1H T1 and T1ρ) for the drug and individual polymer for each set of ASDs were measured to evaluate phase homogeneity. On the basis of proton relaxation measurements, it was revealed that FEL:PVP and FEL:PVP/VA ASDs exhibited better compositional homogeneity than FEL:PVAc ASDs. The strength and the extent of H-bonding were studied by using 13C SSNMR spectra. In addition, deconvolution of the carbonyl region of amorphous FEL revealed that 40% of amorphous FEL mols. were hydrogen bonded (H-bonded) through dimers and the remaining 60% were free/non H-bonded. The dimer fraction decreased as the polymer content increased for each set of ASDs, while the free fraction increased. This indicated that the polymers containing hydrogen bond acceptor groups disrupted dimers and formed intermol. H-bonding interactions with FEL. The strength and extent of FEL:polymer H-bonding was rank ordered as PVP > PVP/VA > PVAc. These findings were also confirmed through DFT calculations on these systems. Our results suggest that drug-polymer H-bonding interaction may impact the phase homogeneity in ASDs formulated by a specific method. The data from the current study further demonstrate that SSNMR is a powerful tool for characterizing phase homogeneity in ASDs with sub-50 nm resolution In addition, SSNMR can provide insights into drug-polymer interactions and speciation in ASDs.

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, HPLC of Formula: 72509-76-3.

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

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

Joyce, Paul published the artcileTIRF Microscopy-Based Monitoring of Drug Permeation Across a Lipid Membrane Supported on Mesoporous Silica, SDS of cas: 72509-76-3, the main research area is felodipine drug permeation lipid membrane mesoporous silica; drug delivery; membrane permeation; mesoporous silica; supported lipid bilayer; total internal reflection fluorescence.

There is an urgent demand for analytic approaches that enable precise and representative quantification of the transport of biol. active compounds across cellular membranes. In this study, we established a new means to monitor membrane permeation kinetics, using total internal reflection fluorescence microscopy confined to a �00 nm thick mesoporous silica substrate, positioned underneath a planar supported cell membrane mimic. This way, we demonstrate spatiotemporally resolved membrane permeation kinetics of a small-mol. model drug, felodipine, while simultaneously controlling the integrity of, and monitoring the drug binding to, the cell membrane mimic. By contrasting the permeation behavior of pure felodipine with felodipine coupled to the permeability enhancer caprylate (C8), we provide evidence for C8-facilitated transport across lipid membranes, thus validating the potential for this approach to successfully quantify carrier system-induced changes to cellular membrane permeation.

Angewandte Chemie, International Edition published new progress about Blood-brain barrier. 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

Zhang, Shujuan published the artcileBile acid transporter mediated STC/Soluplus self-assembled hybrid nanoparticles for enhancing the oral drug bioavailability, Synthetic Route of 72509-76-3, the main research area is sodium taurocholate Soluplus nanoparticle bioavailability bile acid transporter; ASBT; Felodipine; P4; Self-assembled hybrid nanoparticles; Sodium taurocholate; Soluplus.

The nano-particulate system for oral delivery faces a big challenge across the gastrointestinal bio-barriers. The aim was to explore the potential applications of bile acid transporter mediated the self-assembled hybrid nanoparticles (SHNPs) of sodium taurocholate (STC) and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol (Soluplus) for augmenting the oral delivery of poorly water-soluble drugs. Felodipine (FLDP) was chosen as a model drug. The self-assembly of STC with Soluplus to load FLDP and the microstructure of the SHNPs were confirmed using mol. simulation, STC determination by high performance liquid chromatog. (HPLC) and transmission electron microscope. Results showed that STC was integrated with Soluplus on the surface of nanoparticles by hydrophobic interactions. The permeability of FLDP loaded STC/Soluplus SHNPs was STC dependent in the ileum, which was inhibited by the higher concentrations of STC and the inhibitor of apical sodium-dependent bile acid transporter (ASBT). STC/Soluplus (1:9) SHNPs significantly improved the drug loading of FLDP, achieved the highest permeability of FLDP and realized 1.6-fold of the area under the curve (AUC) of Soluplus self-assembled nanoparticles (SNPs). A water-quenching fluorescent probe P4 was loaded into the STC/Soluplus SHNPs, which verified that the SHNPs were transferred intactly across the ileum. In conclusion, STC/Soluplus SHNPs via ASBT are a potential strategy for enhancing the oral bioavailability of poorly water-soluble drugs.

International Journal of Pharmaceutics (Amsterdam, Netherlands) published new progress about Drug bioavailability. 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 artcileInsights into Dissolution and Solution Chemistry of Multidrug Formulations of Antihypertensive Drugs, COA of Formula: C18H19Cl2NO4, the main research area is antihypertensive dissolution solubility supersaturation formulation; amorphous; fixed dose combinations; multidrug formulations; solubility; supersaturation.

Using fixed dose combinations of drugs instead of administering drugs sep. can be beneficial for both patients and the health care system, but the current understanding of how multidrug formulations work at the mol. level is still in its infancy. Here, we explore dissolution, solubility, and supersaturation of various drug combinations in amorphous formulations. The effect of chem. structural similarity on combination behavior was investigated by using structurally related compounds of both drugs. The effect of polymer type on solution behavior was also evaluated using chem. diverse polymers. Indapamide (IPM) concentration decreased when combined with felodipine (FDN) or its analogs, which occurred even when the IPM solution was undersaturated The extent of solubility decrease of FDN was less than that of IPM from the dissolution of an equimolar formulation of the drugs. No significant solubility decrease was observed for FDN at low contents of IPM which was also observed for other dihydropyridines, whereas FDN decreases at high contents of IPM. This was explained by the complex nature of the colloidal precipitates of the combinations which impacts the chem. potential of the drugs in solution at different levels. The maximum achievable concentration of FDN and IPM during dissolution of the polyvinylpyrrolidone-based amorphous solid dispersion was higher than the value measured with the hydroxypropyl methylcellulose acetate succinate-based formulation. This emphasizes the significance of mol. properties and chem. diversity of drugs and polymers on solution chem. and solubility profiles. These findings may apply to drugs administered as a single dosage form or in sep. dosage forms and hence need to be well controlled to assure effective treatments and patient safety.

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, COA of Formula: C18H19Cl2NO4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem