Day: November 30, 2022

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

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

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

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

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

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

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

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

Meere, Martin published the artcileModelling phase separation in amorphous solid dispersions, Synthetic Route of 72509-76-3, the main research area is amorphous solid dispersion phase separation; Amorphous solid dispersion; Drug diffusion; Mathematical model; Phase separation.

Much work has been devoted to analyzing thermodn. models for solid dispersions with a view to identifying regions in the phase diagram where amorphous phase separation or drug recrystallization can occur. However, detailed partial differential equation non-equilibrium models that track the evolution of solid dispersions in time and space are lacking. Hence theor. predictions for the timescale over which phase separation occurs in a solid dispersion are not available. In this paper, we address some of these deficiencies by (i) constructing a general multicomponent diffusion model for a dissolving solid dispersion; (ii) specializing the model to a binary drug/polymer system in storage; (iii) deriving an effective concentration dependent drug diffusion coefficient for the binary system, thereby obtaining a theor. prediction for the timescale over which phase separation occurs; (iv) calculating the phase diagram for the Felodipine/HPMCAS system; and (iv) presenting a detailed numerical investigation of the Felodipine/HPMCAS system assuming a Flory-Huggins activity coefficient The numerical simulations exhibit numerous interesting phenomena, such as the formation of polymer droplets and strings, Ostwald ripening/coarsening, phase inversion, and droplet-to-string transitions. A numerical simulation of the fabrication process for a solid dispersion in a hot melt extruder was also presented. Solid dispersions are products that contain mixtures of drug and other materials e.g. polymer. These are liable to sep.-out over time – a phenomenon known as phase separation This means that it is possible the product differs both compositionally and structurally between the time of manufacture and the time it is taken by the patient, leading to poor bioavailability and so ultimately the shelf-life of the product has to be reduced. Theor. predictions for the timescale over which phase separation occurs are not currently available. Also lacking are detailed partial differential equation non-equilibrium models that track the evolution of solid dispersions in time and space. This study addresses these issues, before presenting a detailed investigation of a particular drug-polymer system.

Acta Biomaterialia 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

Sarabu, Sandeep published the artcileHypromellose acetate succinate based amorphous solid dispersions via hot melt extrusion: Effect of drug physicochemical properties, Formula: C17H18N2O6, the main research area is hypromellose acetate succinate amorphous solid dispersion hot melt extrusion; Efavirenz; HME; HPMCAS; Nifedipine; Solid dispersions; Supersaturation.

In this study, the impact of drug and hydroxypropyl methylcellulose acetate succinate (HPMCAS) grades physicochem. properties on extrusion process, dissolution and stability of the hot melt extruded amorphous solid dispersions (ASDs) of nifedipine and efavirenz was investigated. Incorporation of drugs affected the extrusion temperature required for solid dispersion preparation Differential scanning calorimetry and powder X-ray diffraction studies confirmed the amorphous conversion of the drugs in the prepared formulations. The amorphous nature of ASDs was unchanged after 3 mo of stability testing at 40°C and 75% relative humidity. The dissolution efficiency of the ASDs was dependent on the log P of the drug. The inhibitory effect of HPMCAS on drug precipitation was dependent on the hydrophobic interactions between drug and polymer, polymer grade, and dose of the drug. The dissolution efficiency and dissolution rate of the ASDs were dependent on the log P of the drug and solubility and hydrophilicity of the polymer grade resp. The inhibitory effect of HPMCAS on drug precipitation was dependent on the hydrophobic interactions between drug and polymer, polymer grade, and the dissolution dose of the drug.

Carbohydrate Polymers 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, Formula: C17H18N2O6.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem