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Volume 60, Issue 11
Displaying 1-19 of 19 articles from this issue
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Regular Articles
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Zhe Fang, Su Yang Jeong, Hyun Ah Jung, Jae Sue Choi, Byung Sun Min, Mi ...Article type: Regular Article
2012 Volume 60 Issue 11 Pages 1351-1358
Published: November 01, 2012
Released on J-STAGE: November 01, 2012
JOURNAL FREE ACCESSActivity-directed isolation of the n-hexane and dichloromethane fractions of Capsosiphon fulvescens resulted in the identification of four new glycolipids (1–3): (2S)-1-O-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-2-O-(4Z,7Z,10Z,13Z-hexadecatetraenoyl)-3-O-β-D-galactopyranosyl glycerol (1, capsofulvesin A), (2S)-l-O-(9Z,12Z,15Z-octadecatrienoyl)-2-O-(10Z,13Z-hexadecadienoyl)-3-O-β-D-galactopyranosyl glycerol (2, capsofulvesin B), (2S)-1-O-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-3-O-β-D-galacatopyranosyl glycerol (3, capsofulvesin C). Compounds 1–6 exhibited acetylcholinesterase (AChE) inhibitory activities with IC50 values ranging from 50.90 to 82.83 µM, whereas 2–6 showed butyrylcholinesterase (BChE) inhibitory activities with IC50 values of 114.75–185.55 µM. Although most of the compounds isolated lacked scavenging activity for 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and peroxynitrite (ONOO−), compound 8 showed ONOO− scavenging activity with an IC50 value of 26.23 µg/mL.View full abstractDownload PDF (451K) -
Genki Terashi, Makoto Oosawa, Yuuki Nakamura, Kazuhiko Kanou, Mayuko T ...Article type: Regular Article
2012 Volume 60 Issue 11 Pages 1359-1365
Published: November 01, 2012
Released on J-STAGE: November 01, 2012
JOURNAL FREE ACCESSIn protein structure prediction, such as template-based modeling and free modeling (ab initio modeling), the step that assesses the quality of protein models is very important. We have developed a model quality assessment (QA) program United3D that uses an optimized clustering method and a simple Cα atom contact-based potential. United3D automatically estimates the quality scores (Qscore) of predicted protein models that are highly correlated with the actual quality (GDT_TS). The performance of United3D was tested in the ninth Critical Assessment of protein Structure Prediction (CASP9) experiment. In CASP9, United3D showed the lowest average loss of GDT_TS (5.3) among the QA methods participated in CASP9. This result indicates that the performance of United3D to identify the high quality models from the models predicted by CASP9 servers on 116 targets was best among the QA methods that were tested in CASP9. United3D also produced high average Pearson correlation coefficients (0.93) and acceptable Kendall rank correlation coefficients (0.68) between the Qscore and GDT_TS. This performance was competitive with the other top ranked QA methods that were tested in CASP9. These results indicate that United3D is a useful tool for selecting high quality models from many candidate model structures provided by various modeling methods. United3D will improve the accuracy of protein structure prediction.View full abstractDownload PDF (888K) -
Atsushi Sakurai, Kazuhiro Sako, Yoshie MaitaniArticle type: Regular Article
2012 Volume 60 Issue 11 Pages 1366-1371
Published: November 01, 2012
Released on J-STAGE: November 01, 2012
JOURNAL FREE ACCESSIn this study, we investigated the effect of manufacturing factors such as particle size, water content and manufacturing method on the physical stability and solubility of solid dispersion formulations of a low-glass-transition-temperature (Tg) drug. Solid dispersions were prepared from polyvinylpyrrolidone (PVP) and hydroxypropylmethylcellulose (HPMC) by hot melt extrusion or spray drying. Water content of solid dispersions prepared by hot melt extrusion determined by dynamic moisture sorption measurement was increased drastically with relative humidity below a certain level of particle size. The blends with a lower water content (0.8%) prepared by hot melt extrusion during storage were more stable than those with a higher water content (3.5%) prepared by spray drying, which caused rapid recrystallization. Physical stability in the hot melt blends may be attributed to reduced molecular mobility due to a higher Tg. Dissolution study revealed that solid dispersions prepared by hot melt extrusion with the smallest particle size showed decreased solubility, attributed to reduced wetting properties (surface energy), which is not predictable by the Noyes–Whitney equation. Taken together, these results indicate that the control of particle size concerned in water content or wetting properties is critical to ensuring the physical stability or enhancing solubility of low-Tg drugs. Further, hot melt extrusion, which can reduce water content, is a suitable manufacturing method for solid dispersions of low-Tg drugs.View full abstractDownload PDF (480K) -
Camila Mareco Bento Leite Silva, Francielle Pelegrin Garcia, Jean Henr ...Article type: Regular Article
2012 Volume 60 Issue 11 Pages 1372-1379
Published: November 01, 2012
Released on J-STAGE: November 01, 2012
JOURNAL FREE ACCESSA series of novel benzo[4,5]canthin-6-ones, bearing the N′-(substituted benzylidene)-carbohydrazide (11a–e) and N-alkylcarboxamide (13a–g) moieties at position-2, were synthesized and screened for their in vitro antitumor activity, against seven human cancer cell lines, and for antitrypanosomal and antileishmanial activities against Trypanosoma cruzi and Leishmania amazonensis. The results indicated that N-methylpiperazyl-6-oxobenzo[4,5]canthine-2-carboxamide (13f) displayed potent antitumor activity with IC50 values in the range of 1.15–8.46 µM for all cell lines tested. Compounds 13f and 13g bearing an N-methylpiperazylcarboxamide and N-morpholylcarboxamide at C-2, respectively, showed potent activities towards both Trypanosoma cruzi and Leishmania amazonensis parasites, with IC50 in the range of 0.4 to 16.70 µM.View full abstractDownload PDF (612K) -
Maya Fujiwara, Masafumi Dohi, Tomoko Otsuka, Kazunari Yamashita, Kazuh ...Article type: Regular Article
2012 Volume 60 Issue 11 Pages 1380-1386
Published: November 01, 2012
Released on J-STAGE: November 01, 2012
JOURNAL FREE ACCESSWe evaluated models for predicting spray mist diameter suitable for scaling-up the fluidized bed granulation process. By precise selection of experimental conditions, we were able to identify a suitable prediction model that considers changes in binder solution, nozzle dimension, and spray conditions. We used hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC), or polyvinylpyrrolidone (PVP) binder solutions, which are commonly employed by the pharmaceutical industry. Nozzle dimension and spray conditions for oral dosing were carefully selected to reflect manufacturing and small (1/10) scale process conditions. We were able to demonstrate that the prediction model proposed by Mulhem optimally estimated spray mist diameter when each coefficient was modified. Moreover, we developed a simple scale-up rule to produce the same spray mist diameter at different process scales. We confirmed that the Rosin–Rammler distribution could be applied to this process, and that its distribution coefficient was 1.43–1.72 regardless of binder solution, spray condition, or nozzle dimension.View full abstractDownload PDF (775K) -
Letícia Lenz Sfair, Caren Gobetti, Maximiliano da Silva Sangoi, ...Article type: Regular Article
2012 Volume 60 Issue 11 Pages 1387-1394
Published: November 01, 2012
Released on J-STAGE: November 01, 2012
JOURNAL FREE ACCESSA simple, stability-indicating micellar electrokinetic chromatography (MEKC) method was developed and validated for the analysis of mianserin hydrochloride in coated tablets. The method employed (hydroxymethyl)aminomethane (TRIS) 50 mM to which sodium dodecyl sulfate (SDS) 50 mM was added at pH 10.6 as the electrolyte and the voltage applied was 25 kV. The capillary used was 48.5 cm long (40.0 cm effective length and 50.0 µm i.d.) and the detection wavelength was 220 nm. Tetracycline was used as internal standard. The method was validated in accordance with the International Conference on Harmonization (ICH) requirements, which involved specificity, linearity, precision, accuracy and robustness. The stability-indicating capability of the method was established by enforced degradation studies combined with peak purity assessment using photodiode array detection. The degradation products formed under photolytic and oxidative conditions were investigated by electrospray ionization mass spectrometry. The method was linear over the concentration range of 50–130 µg/mL. The method was precise as demonstrated by an inter-day and intra-day relative standard deviation of less than 2.0%. The proposed validated MEKC method showed recoveries between 98.16 and 102.80% of the nominal contents. The Plackett–Burman design was applied for the robustness test in order to examine potential sources of variability by screening a large number of factors in a relatively small number of experiments.View full abstractDownload PDF (593K) -
Maiko Hamada, Kunitomo Adachi, Hidemasa Hikawa, Yuusaku YokoyamaArticle type: Regular Article
2012 Volume 60 Issue 11 Pages 1395-1398
Published: November 01, 2012
Released on J-STAGE: November 01, 2012
JOURNAL FREE ACCESSA concise synthesis of a useful intermediate 10 for the preparation of fingolimod (FTY-720) analogs was achieved by utilizing a chemoselective Sonogashira reaction of trihalobenzene 12 with alkyne 13. The reaction proceeded with high selectivity to give alkyne 11 containing the dihalobenzene moiety in good yield. Compound 11 was converted into intermediate 10 by hydrogenation without reduction of the halogen atoms.View full abstractDownload PDF (485K) -
Jin Maeda, Tatsuya Suzuki, Kozo TakayamaArticle type: Regular Article
2012 Volume 60 Issue 11 Pages 1399-1408
Published: November 01, 2012
Released on J-STAGE: November 01, 2012
JOURNAL FREE ACCESSDesign spaces for multiple dose strengths of tablets were constructed using a Bayesian estimation method with one set of design of experiments (DoE) of only the highest dose-strength tablet. The lubricant blending process for theophylline tablets with dose strengths of 100, 50, and 25 mg is used as a model manufacturing process in order to construct design spaces. The DoE was conducted using various Froude numbers (X1) and blending times (X2) for theophylline 100-mg tablet. The response surfaces, design space, and their reliability of the compression rate of the powder mixture (Y1), tablet hardness (Y2), and dissolution rate (Y3) of the 100-mg tablet were calculated using multivariate spline interpolation, a bootstrap resampling technique, and self-organizing map clustering. Three experiments under an optimal condition and two experiments under other conditions were performed using 50- and 25-mg tablets, respectively. The response surfaces of the highest-strength tablet were corrected to those of the lower-strength tablets by Bayesian estimation using the manufacturing data of the lower-strength tablets. Experiments under three additional sets of conditions of lower-strength tablets showed that the corrected design space made it possible to predict the quality of lower-strength tablets more precisely than the design space of the highest-strength tablet. This approach is useful for constructing design spaces of tablets with multiple strengths.View full abstractDownload PDF (12754K) -
Bijay Kumar Poudel, Nirmal Marasini, Tuan Hiep Tran, Han-Gon Choi, Chu ...Article type: Regular Article
2012 Volume 60 Issue 11 Pages 1409-1418
Published: November 01, 2012
Released on J-STAGE: November 01, 2012
JOURNAL FREE ACCESSThe aim of the present research was to systematically investigate the main, interaction and the quadratic effects of formulation variables on the performance of self-microemulsifying drug delivery system (SMEDDS) of valsartan using design of experiment. A 17-run Box–Behnken design (BBD) with 3-factors and 3-levels, including 5 replicates at the centre point, was used for fitting a 2nd-order response surface. After the preliminary screening, Labrafil M 2125 CS as oil, Tween 20 as surfactant and Capryol 90 as co-surfactant were taken as independent variables. The dependent factors (responses) were particle size, polydispersity index (PDI), dissolution after 15 min and equilibrium solubility. Coefficients were estimated by regression analysis and the model adequacy was checked by an F-test and the determination coefficient (R2). All the responses were optimized simultaneously by using desirability function. Our results demonstrated marked main and interaction effects of independent factors on responses. The optimized formulation consisted of 26.8% (w/w) oil, 60.1% (w/w) surfactant and 13.1% (w/w) co-surfactant, and showed average micelle size of 90.7 nm and 0.246 PDI, 91.2% dissolution after 15 min and 226.7 mg/g equilibrium solubility. For the optimized formulation, predicted value and experimental value were in close agreement. After oral administration, the optimized formulation gave more than 2-fold higher area under curve (AUC) and about 6-fold higher Cmax in rats than valsartan powder (p<0.05). The BBD facilitated in the better understanding of inherent relationship of formulation variables with the responses and in the optimization of valsartan SMEDDS in relatively time and labor effective manner.View full abstractDownload PDF (1759K) -
Yoshihiro Hayashi, Etsuko Oshima, Jin Maeda, Yoshinori Onuki, Yasuko O ...Article type: Regular Article
2012 Volume 60 Issue 11 Pages 1419-1425
Published: November 01, 2012
Released on J-STAGE: November 01, 2012
Advance online publication: August 10, 2012JOURNAL FREE ACCESSA multivariate statistical technique was applied to the design of an orally disintegrating tablet and to clarify the causal correlation among variables of the manufacturing process and pharmaceutical responses. Orally disintegrating tablets (ODTs) composed mainly of mannitol were prepared via the wet-granulation method using crystal transition from the δ to the β form of mannitol. Process parameters (water amounts (X1), kneading time (X2), compression force (X3), and amounts of magnesium stearate (X4)) were optimized using a nonlinear response surface method (RSM) incorporating a thin plate spline interpolation (RSM-S). The results of a verification study revealed that the experimental responses, such as tensile strength and disintegration time, coincided well with the predictions. A latent structure analysis of the pharmaceutical formulations of the tablet performed using a Bayesian network led to the clear visualization of a causal connection among variables of the manufacturing process and tablet characteristics. The quantity of β-mannitol in the granules (Qβ) was affected by X2 and influenced all granule properties. The specific surface area of the granules was affected by X1 and Qβ and had an effect on all tablet characteristics. Moreover, the causal relationships among the variables were clarified by inferring conditional probability distributions. These techniques provide a better understanding of the complicated latent structure among variables of the manufacturing process and tablet characteristics.View full abstractDownload PDF (2129K) -
Khaled Darwish, Ismail Salama, Samia Mostafa, Mohamed El-SadekArticle type: Regular Article
2012 Volume 60 Issue 11 Pages 1426-1436
Published: November 01, 2012
Released on J-STAGE: November 01, 2012
JOURNAL FREE ACCESSNew, simple, rapid and precise reversed-phase high-performance liquid chromatographic method was developed for the simultaneous determination of orphenadrine citrate, caffeine and aspirin in presence of aspirin degradation products, orphenadrine citrate and caffeine process related impurities, and excipients. Good resolution and quantization were achieved on reversed-phase column [Phenomenex™ Luna ODS C18 (25 cm×4.6 mm, 5 µm particles)]. Gradient elution based on; eluant [A]: 0.1% triethylamine in aqueous potassium dihydrogen phosphate buffer (50 mM; pH 3.0), while as, eluant [B]: acetonitrile, at a flow rate of 1.5 mL min−1. UV quantitation was set at 215 nm. Linearity was exhibited for orphenadrine citrate, caffeine and aspirin within 0.5–150, 0.5–360 or 0.7–301 µg mL−1 ranges, respectively. Satisfactory validation results were ascertained in terms of low limits of quantiation (6.33×10−2–7.94×10−2), mean percentage recovery (98.9–101.4%), precision (<2%) and robustness. The proposed method was proved to be specific, robust and accurate for the determination of cited drugs in pharmaceutical preparations in presence of their degradation products.View full abstractDownload PDF (816K) -
Yi Shen, Jianhua Zou, Dan Xie, Hanlin Ge, Xiuping Cao, Jungui DaiArticle type: Regular Article
2012 Volume 60 Issue 11 Pages 1437-1441
Published: November 01, 2012
Released on J-STAGE: November 01, 2012
JOURNAL FREE ACCESSA new butyrolactone, 7″-hydroxybutyrolactone III (1) and three new cycloheptanetriones, terretrione A–C (2–4), together with five known compounds, butyrolactone I, cyclo(Leu-Pro), cyclo(Val-Pro), cyclo(Ile-Pro), cyclo(Phe-Pro), were isolated from mangrove-associated marine fungus Aspergillus terreus. The structures of these compounds were elucidated on the basis of physical data analysis (NMR, high resolution-electrospray ionization (HR-ESI)-MS), especially by 2D-NMR techniques. These compounds showed weak cytotoxicity in vitro against HCT-8, Bel-7402, BGC-823, A2780 cell lines.View full abstractDownload PDF (457K) -
Toshifumi Dohi, Tohru Kamitanaka, Eisuke Mochizuki, Motoki Ito, Yasuyu ...Article type: Regular Article
2012 Volume 60 Issue 11 Pages 1442-1447
Published: November 01, 2012
Released on J-STAGE: November 01, 2012
JOURNAL FREE ACCESSBy utilizing a specific solvent and highly active 2-azaadamantane-N-oxyl (AZADO) as an organocatalyst, we have improved the recycling protocol of the adamatane reagent 1 to be faster and more operationally simple for the hypervalent iodine/nitroxyl radical mediated alcohol oxidation. This very mild system can efficiently mediate the oxidation of a range of alcohols to carbonyl compounds with a broad substrate scope, and after the reactions, the reduced adamantane tetraiodide 1′, which automatically precipitated from the reaction mixtures as the reactions progresses, could be directly recovered by filtration.View full abstractDownload PDF (677K)
Notes
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Bo Li, Wei-Dong Zhang, Yi-Ren He, Lu Lu, De-Yun Kong, Yun-Heng ShenArticle type: Note
2012 Volume 60 Issue 11 Pages 1448-1452
Published: November 01, 2012
Released on J-STAGE: November 01, 2012
Advance online publication: August 20, 2012JOURNAL FREE ACCESS
Supplementary materialThree new alkaloids (1–3), together with ten known alkaloids, were isolated from the ethanolic extract of the whole plants of Lycopodium japonicum THUNB. Their structures were elucidated on the basis of spectroscopic analysis, including MS and NMR methods. All alkaloids isolated were assayed for cytotoxic activity against four human cancer cell lines and acetylcholinesterase (AChE) inhibitory activity. No alkaloid showed either cytotoxic activity against four human cancer cell lines or AChE inhibitory activity.View full abstractDownload PDF (670K) -
Ing-Jy Tseng, Shiow-Yunn Sheu, Ying-Tzu Chen, Chu-Yun Huang, Ching-Tun ...Article type: Note
2012 Volume 60 Issue 11 Pages 1453-1457
Published: November 01, 2012
Released on J-STAGE: November 01, 2012
JOURNAL FREE ACCESSThe lab made an effort to prepare some biological active cantharidinimines by heating the reactant 1 and 2a–g, 5h–i and 7j–r amines to suitable temperature with ethanol to provide 18 N-thiazolyl-, sulfanyl-, aminopyridyl-, bromopyridyl-, alkylpyridyl- and hydroxypyridylcantharidinimines 3a–g, 4a–c, 6h–i and 8j–r in yield of 4–77% (Chart 1). These cantharidinimine derivatives were tested for their capabilities to suppress growth of the human carcinoma cell lines, HL-60, MCF7, Neuro-2a and A549, because the incidence rate is more prominent in Asian countries than western countries. Compounds 3c–d and 6h–i were found to have some antitumor activity in HL-60 but less activity in MCF cell and compounds 8j–l displayed some inhibition effects to A549 cell line, but less effect to Neuro-2a cell line. Compounds 8m–r had no cytotoxic effect against both cell lines. The cytotoxic effects of these cantharidinimine compounds seemed to be better than the cantharidinimide compounds which we had mentioned several years ago.View full abstractDownload PDF (514K) -
Huquan Gao, Lianqing Zhang, Tianjiao Zhu, Qianqun Gu, Dehai LiArticle type: Note
2012 Volume 60 Issue 11 Pages 1458-1460
Published: November 01, 2012
Released on J-STAGE: November 01, 2012
Advance online publication: September 04, 2012JOURNAL FREE ACCESSOne new pyrrolyl 4-quinolinone alkaloid, penicinoline E (1), together with three known deriverites, methyl-penicinoline (2), penicinoline (3), and quinolactacide (4), were isolated from the marine-derived fungus Penicillium sp. ghq208. The structures of these isolated compounds were elucidated by spectroscopic methods. Compounds (2, 3) exhibited moderate cytotoxicities against the HepG2 cell line with IC50 values of 11.3 and 13.2 µM, respectively.View full abstractDownload PDF (307K) -
Yukiko Akai, Yukako Tabuchi, Kumiko Ando, Azusa Ito, Yoko Sakata, Ikuo ...Article type: Note
2012 Volume 60 Issue 11 Pages 1461-1467
Published: November 01, 2012
Released on J-STAGE: November 01, 2012
JOURNAL FREE ACCESS
Supplementary materialA series of benzo[b]furan derivatives having a five-membered heterocyclic substituent at the 2-position were prepared from 2-(1-chloro-2-formylvinyl)benzo[b]furans (2) and 2-(4-alkylcarbamoylbuta-1,3-dienyl)benzo[b]furans. These 2-heterocyclic benzo[b]furans were evaluated for their cysteinyl leukotriene receptor (cysLT1, cysLT2) inhibitory activity. Several compounds showed moderate inhibition of calcium mobilization in HEK 293T-cysLT2 or CHO-cysLT1 cells.View full abstractDownload PDF (1260K) -
In-Hwan Beak, Min-Soo KimArticle type: Note
2012 Volume 60 Issue 11 Pages 1468-1473
Published: November 01, 2012
Released on J-STAGE: November 01, 2012
JOURNAL FREE ACCESSIn this study, amorphous solid dispersions containing dutasteride and various excipients, manufactured by spray-drying processes, were characterized to determine the effects on their ability to form supersaturated solutions and to identify the effects of supersaturation on increasing the bioavailability of dutasteride. The excipients included Eudragit E, hydroxypropyl-β-cyclodextrin (HP-β-CD), hydroxypropyl cellulose (HPC), hydroxypropylmethyl cellulose (HPMC), and polyvinylpyrrolidone (PVP K30). A solid dispersion with Eudragit E displayed a high maximum supersaturation with extended supersaturation, compared with a water-soluble polymer. The maximum concentration and the degree of supersaturation increased in the following order: PVP K30<HP-β-CD=HPC<HPMC<Eudragit E. Oral drug absorption of solid dispersions was obviously higher when compared with micronized raw material and physical mixtures, in the following order: HPC<HPMC<Eudragit E. In fact, the AUC0→24 h and Cmax of dutasteride increased with supersaturation concentration. These results suggest that amorphous solid dispersions containing Eudragit E, formed by a spray-drying process, offer enhanced supersaturation characteristics, leading to increased oral absorption of dutasteride.View full abstractDownload PDF (694K) -
Wen Gu, Chao QiaoArticle type: Note
2012 Volume 60 Issue 11 Pages 1474-1477
Published: November 01, 2012
Released on J-STAGE: November 01, 2012
Advance online publication: August 27, 2012JOURNAL FREE ACCESSTwo new furandiones named asperterone B (1) and C (2) together with four known metabolites (3–6) were isolated from the liquid culture of the endophytic fungus Aspergillus terreus MHL-P22 residing in the fresh leaves of Malus halliana. The structures of the new compounds were elucidated by analysis of their MS, IR, 1D- and 2D-NMR spectra. 1 and 2 showed moderate cytotoxic activities against human colorectal carcinoma SW1116 cells with IC50 values of 57.5 and 71.0 µM, respectively. The biosynthetic pathway for 1, 2 and their analogues was also postulated and briefly discussed.View full abstractDownload PDF (459K)
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