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Chem Pharm Bull [journal]
- Effect of Process Variables on the Drucker-Prager Cap Model and Residual Stress Distribution of Tablets Estimated by the Finite Element Method. [JOURNAL ARTICLE]
- Chem Pharm Bull (Tokyo) 2014 Aug 9.
A multivariate statistical technique was applied to clarify the causal correlation between variables in the manufacturing process and the residual stress distribution of tablets. Theophylline tablets were prepared according to a Box-Behnken design using the wet granulation method. Water amounts (X1), kneading time (X2), lubricant-mixing time (X3), and compression force (X4) were selected as design variables. The Drucker-Prager cap (DPC) model was selected as the method for modeling the mechanical behavior of pharmaceutical powders. Simulation parameters, such as Young's modulus, Poisson rate, internal friction angle, plastic deformation parameters, and initial density of the powder, were measured. Multiple regression analysis demonstrated that the simulation parameters were significantly affected by process variables. The constructed DPC models were fed into the analysis using the finite element method (FEM), and the mechanical behavior of pharmaceutical powders during the tableting process was analyzed using the FEM. The results of this analysis revealed that the residual stress distribution of tablets increased with increasing X4. Moreover, an interaction between X2 and X3 also had an effect on shear and the x-axial residual stress of tablets. Bayesian network analysis revealed causal relationships between the process variables, simulation parameters, residual stress distribution, and pharmaceutical responses of tablets. These results demonstrated the potential of the FEM as a tool to help improve our understanding of the residual stress of tablets and to optimize process variables, which not only affect tablet characteristics, but also are risks of causing tableting problems.
- Screening for Protein Kinase C Ligands Using Fluorescence Resonance Energy Transfer. [JOURNAL ARTICLE]
- Chem Pharm Bull (Tokyo) 2014 Aug 8.
Protein kinase C (PKC) is correlated with cell signaling pathways and also receives attention as a therapeutic target for cancer and Alzheimer-type dementia. The application of Förster/fluorescence resonance energy transfer (FRET) phenomena to detect binding between proteins and small molecules, for example, PKC and its ligands, underlies a fluorescence-based assay method suitable for high-throughput screening. To accelerate studies on PKC functions in processing signals using small molecules and the development of drugs that target PKC, novel methods for the assessment of the PKC binding affinity of compounds are necessary. We previously developed solvatochromic fluorophore-based methods for that assessment. In this study, a novel method for a FRET-based PKC binding assay was developed and is expected to overcome the limitations of solvatochromic fluorophores.
- Design and evaluation of a brinzolamide drug-resin in situ thermosensitive gelling system for sustained ophthalmic drug delivery. [JOURNAL ARTICLE]
- Chem Pharm Bull (Tokyo) 2014 Aug 5.
In this study a brinzolamide drug-resin ophthalmic thermosensitive in situ gelling system was developed and evaluated. Brinzolamide was combined with ion exchange resins to prolong the retention time of drugs in the eye and to reduce ocular and systemic side effects. Poloxamer F127 was used as gelling vehicle in combination with carbopol 934P, which acted as a viscosity-enhancing agent. They were prepared using the cold method. The optimized formulation exhibited a sol-gel transition at 33.2±1.1°C with pseudoplastic flow behavior. This formulation was stable and nonirritant to rabbit eyes. In vitro release studies demonstrated diffusion-controlled release of brinzolamide from the combined solutions over a period of 8 h. In vivo evaluation (the elimination of brinzolamide through tears and absorption of brinzolamide in aqueous humor) indicated that the solution combination was better able to retain the drug than commercial preparations. Thus this formulation is safe for ophthalmic use and significantly increases brinzolamide bioavailability in aqueous humor.
- Calysolins X-XIII, Resin Glycosides from Calystegia soldanella, and Their Antiviral Activity toward Herpes Simplex Virus. [Journal Article]
- Chem Pharm Bull (Tokyo) 2014; 62(8):839-44.
Four new resin glycosides having macrolactone structures (jalapins), named calysolins X (1)-XIII (4), were isolated from the leaves, stems, and roots of Calystegia soldanella ROEM. et SCHULT. (Convolvulaceae). Their structures were determined on the basis of spectroscopic data as well as chemical evidence. The sugar moieties of 1-4 were partially acylated by some organic acids, including tiglic acid, 2S-methylbutyric acid, and 2S,3S-nilic acid. Additionally, the antiviral activity of 1-4 toward herpes simplex virus type 1 was evaluated. All the compounds showed antiviral activity.
- Crystallization-Induced Diastereomeric Transformation of N-2'-t-Butyl-6'-iodobenzoyl-3-bromocarbazole. [Journal Article]
- Chem Pharm Bull (Tokyo) 2014; 62(8):836-8.
We previously reported the atropisomeric properties of 2'-t-butyl-6'-iodo-substituted N-benzoyl-3-bromocarbazole, i.e., the steric or electronic effects of the substituents restricted the rotation about the N-C7' and C7'-C1' bonds to separate four stereoisomers (cis/trans for the N-C7' axis, aR/aS for the C7'-C1' axis). Furthermore, the 2'-t-butyl-6'-iodo-substituted N-benzoyl 3-bromocarbazole was confirmed to be a gear molecule, in which the rotation about the C7'-C1' bond was in perfect concert with that about the N-C7' bond. Herein, we report a unique crystallization-induced diastereomeric transformation found in this molecule. In the isolation process, where the product is recrystallized from the diastereoisomeric mixture, in situ isomerization and selective crystallization could lead to a diastereomeric transformation, and a mixture of diastereomers (trans/cis=54 : 46) was converted to trans-isomer-enriched crystals (trans/cis>96 : 4) in 95% yield. Conformational analysis clarified the preference for the trans versus cis isomer.
- Four New Acylated Glycosidic Acid Methyl Esters Isolated from the Convolvulin Fraction of Seeds of Quamoclit pennata after Treatment with Indium(III) Chloride in Methanol. [Journal Article]
- Chem Pharm Bull (Tokyo) 2014; 62(8):830-5.
Four new acylated glycosidic acid methyl esters were isolated after treatment of the crude ether-insoluble resin glycoside (convolvulin) fraction obtained from the seeds of Quamoclit pennata BOJER (Convolvulaceae) with indium(III) chloride in methanol. Their structures were elucidated on the basis of spectroscopic data and chemical conversions.
- Synthesis of a Natural Chromenoquinone via the Diels-Alder Reaction of Pyranobenzyne and Furan. [Journal Article]
- Chem Pharm Bull (Tokyo) 2014; 62(8):820-3.
We describe the total synthesis of angular chromenoquinone 1 isolated from Conospermum plants. Iodophenol, a precursor of pyranobenzyne, was prepared by Claisen rearrangement of an iodoresorcinol derivative. Diels-Alder reaction of the pyranobenzyne and a substituted furan proceeded in low regioselectivity to afford desired 1 and its regioisomer.
- Synthesis and Biological Evaluation of 3-Styrylchromone Derivatives as Free Radical Scavengers and α-Glucosidase Inhibitors. [Journal Article]
- Chem Pharm Bull (Tokyo) 2014; 62(8):810-5.
A series of 3-styrylchromone derivatives (4-20) were synthesized and the structure-activity relationships for α-glucosidase inhibition and antioxidant activities were analyzed. Among the synthesized compounds, compounds 15 and 20, which contain a catechol moiety, showed both potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity (15: EC50=17 µM; 20: EC50=23 µM) and α-glucosidase inhibitory activity (15: IC50=16 µM; 20: IC50=10 µM). Our data suggest that 3-styrylchromone derivatives are novel α-glucosidase inhibitors that have the potential to counteract diet-induced hyperglycemia in diabetes.
- Synthesis of (13)c-lidocaine as a probe of breath test for the evaluation of cytochrome p450 activity. [Journal Article]
- Chem Pharm Bull (Tokyo) 2014; 62(8):806-9.
(13)C-Labeled lidocaine, 2-di[1-(13)C]ethylamino-N-(2,6-dimethylphenyl)acetamide (1), was synthesized from [1-(13)C]acetic acid in six steps, as a probe for a breath test to evaluate in vivo cytochrome P450 activity. The measurement of (13)CO2 in breath was successfully performed following oral administration of (13)C-lidocaine 1 to mice.
- Adsorption of orthophosphoric, pyrophosphoric, and tripolyphosphoric acids from aqueous solutions by calcined gibbsite. [Journal Article]
- Chem Pharm Bull (Tokyo) 2014; 62(8):799-805.
In this research, gibbsite (GB) samples calcined at 200-1000°C (GB200-GB1000) were produced. These GBs were used to adsorb orthophosphoric, pyrophosphoric, and tripolyphosphoric acids from aqueous solutions. The properties (amounts of hydroxyl groups, specific surface areas, mean pore diameters, and solution pHs) of the GBs were investigated, and their adsorption capacities for phosphoric acids evaluated. The amount of hydroxyl groups (0.46 mmol/g) and specific surface area (295.3 m(2)/g) of GB400 were greater than those of the other GBs. The mechanism of phosphoric acid adsorption on the GBs was related to the amount of hydroxyl groups and specific surface area. The optimal pH for phosphoric acid adsorption by GBs was 2.0-3.0. Equilibrium adsorption was reached within 24 h. The adsorption processes followed a pseudo-second-order kinetic model (correlation coefficient, 0.998-0.999). The adsorption capacity increased with increasing temperature. The adsorption isotherm data fitted the Langmuir (correlation coefficient: 0.921-0.992) and Freundlich (correlation coefficient: 0.948-0.997) equations well. Our results will be useful when developing methods for the adsorption of phosphoric acids from aqueous solutions.