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Effect of Solubilizing and Microemulsifying Excipients in Polyethylene Glycol 6000 Solid Dispersion on Enhanced Dissolution and Bioavailability of Ketoconazole

  • Heo, Min-Young;Piao, Zong-Zhu;Kim, Tae-Wan;Cao, Qing-Ri;Kim, Ae-Ra;Lee, Beom-Jin
    • Archives of Pharmacal Research
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    • v.28 no.5
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    • pp.604-611
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    • 2005
  • Polyethylene glycol (PEG) 6000-based solid dispersions (SDs), by incorporating various pharmaceutical excipients or microemulsion systems, were prepared using a fusion method, t o compare the dissolution rates and bioavailabilities in rats. The amorphous structure of the drug in SDs was also characterized by powder X-ray diffractometry (XRD) and differential scanning calorimetry (DSC). The ketoconazole (KT), as an antifungal agent, was selected as a model drug. The dissolution rate of KT increased when solubilizing excipients were incorporated into the PEG-based SDs. When hydrophilic and lipophilic excipients were combined and incorporated into PEG-based SDs, a remarkable enhancement of the dissolution rate was observed. The PEG-based SDs, incorporating a self microemulsifying drug delivery system (SMEDDS) or microemulsion (ME), were also useful at improving the dissolution rate by forming a microemulsion or dispersible particles within the aqueous medium. However, due to the limited solubilization capacity, these PEG-based SDs showed dissolution rates, below 50% in this study, under sink conditions. The PEG-based SD, with no pharmaceutical excipients incorporated, increased the maximum plasma concentration (C$_{max}$) and area under the plasma concentration curve (AUC$_{0-6h}$) two-fold compared to the drug only. The bioavailability was more pronounced in the cases of solubilizing and microemulsifying PEG-based SDs. The thermograms of the PEG-based SDs showed the characteristic peak of the carrier matrix around 60$^{\circ}C$, without a drug peak, indicating that the drug had changed into an amorphous structure. The diffraction pattern of the pure drug showed the drug to be highly crystalline in nature, as indicated by numerous distinctive peaks. The lack of the numerous distinctive peaks of the drug in the PEG-based SDs demonstrated that a high concentration of the drug molecules was dissolved in the solid-state carrier matrix of the amorphous structure. The utilization of oils, fatty acid and surfactant, or their mixtures, in PEG-based SD could be a useful tool to enhance the dissolution and bioavailability of poorly water-soluble drugs by forming solubilizing and microemulsifying systems when exposed to gastrointestinal fluid.

Portal Vein Thrombosis in a Dog with Dirofilariasis (심장사상충에 감염된 개에서 발생한 문정맥혈전증)

  • Yun, Seok-Ju;Cheon, Haeng-Bok;Han, Jae-Ik;Kang, Ji-Houn;Chang, Jin-Hwa;Na, Ki-Jeong;Chang, Dong-Woo
    • Journal of Veterinary Clinics
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    • v.27 no.5
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    • pp.600-604
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    • 2010
  • A ten-year-old female mongrel dog was presented to Veterinary Medical Center, Chungbuk National University with the signs of anorexia, weakness, and hemoglobinuria. Patient had been diagnosed as dirofilariasis based on heartworm antigen test and treated with adulticide (melarsomine) at local hospital one day before admission. On laboratory examinations, there were hypochromic and microcytic regenerative anemia, thrombocytopenia, moderate neutrophilia, and increase ALT, AST, and ALP. Radiographic exam showed main pulmonary artery bulging, pulmonary infiltration and hypervascularity, reduced abdominal serosal detail and mild hepatomegaly. Abdominal ultrasonographic exam showed mild peritoneal effusion and large hyperechoic thrombi at trifurcation of the porta hepatica and the splenic vein. In addition, intraluminal low density area and intravascular filling defect were confirmed on contrast enhanced CT scanning at the same anatomic locations. Patient was treated with anticoagulant and thrombolytic therapy. On day 42 after treatment, complete resolution of thrombi was confirmed via ultrasonography and improvement of clinical signs was observed.

The Tissues and Blood Components of Opsariichthys uncirostris amurensis in the Muddy Water Area (탁수역에 서식하는 끄리의 조직과 혈액 성분의 변화)

  • Shin, Myung-Ja;Lee, Jong-Eun;Seo, Eul-Won
    • Journal of Life Science
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    • v.17 no.1 s.81
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    • pp.97-104
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    • 2007
  • Present study aims to investigate the effect of muddy water on gill and kidney tissues and blood components of Opsariichthys uncirostris amurensis in Imha reservoir. As a result of observing the gill tissues in muddy water with light and scanning electron microscopes, the edema, the exfoliation of epithelial cells and fusion of the secondary lamellae were observed. The space between gill lamellae was irregular, and a lots of muddy debris around the secondary lamellae were observed. In case of kidney tissues, the size of glomerulus was smaller and thickness of basal membrane was broader and the empty space in Bowman's capsule was wider than those of the control. The blood cells of O. uncirostris amurensis in muddy water were increased in number. Of the white blood cells, acidophilic granulocytes were highly distributed, and the shapes were irregular. Among the plasma components, the concentration of TP, ALB, A/G ratio, TG, CHOL, and AST were low, whereas that of the inorganic materials was high. Based on the above results, it is considered that muddy water possibly involves in the decrease of respiratory and excretory rates, giving rise to secondary lesion of tissues.

The Effect of Circle Contact Lens on the Stability of Tear Film (써클콘택트렌즈가 눈물막 안정성에 미치는 영향)

  • Lee, Sehee;Hyung, Sung Min;Koh, Seung Hwan;Park, Mijung;Kim, So Ra
    • Journal of Korean Ophthalmic Optics Society
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    • v.20 no.2
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    • pp.125-131
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    • 2015
  • Purpose: The effect of pigmentation in circle contact lens on lens wearers' tear film stability was investigated in this study. Methods: Non-invasive tear film break-up times of 54 normal eyes before and after lens wearing in twenties and the portion of first tear breakup were measured. The frontal and back surface roughness of circle contact lens was further observed with a scanning electron microscope. The clear lens which was made of hilafilcon B and circle contact lenses which were made of hilafilcon B, polymacon and copolymer of HEMA NVP were tested. Results: Non-invasive tear film breakup time was significantly reduced compared with it before lens wearing. In some case, statistically significant difference in tear film breakup time was also observed between circle contact lenses. The tear file break-up was usually early started in lower than upper portion, and in temporal than nasal portion although there was variation in the lens material. The tear film break-up of circle contact lenses made of hilafilcon B was more commonly observed in peripheral portion(pigmented area) compared with clear contact lens made of same material. Conclusions: The present study revealed that the stability of tear film was affected by wearing circle contact lens and the result seems to be used as the basis for the problem solving that can occur due to the pigmentation when wearing circle contact lens.

Salinity Stress Resistance Offered by Endophytic Fungal Interaction Between Penicillium minioluteum LHL09 and Glycine max. L

  • Khan, Abdul Latif;Hamayun, Muhammad;Ahmad, Nadeem;Hussain, Javid;Kang, Sang-Mo;Kim, Yoon-Ha;Adnan, Muhammad;Tang, Dong-Sheng;Waqas, Muhammad;Radhakrishnan, Ramalingam;Hwang, Young-Hyun;Lee, In-Jung
    • Journal of Microbiology and Biotechnology
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    • v.21 no.9
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    • pp.893-902
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    • 2011
  • Endophytic fungi are little known for their role in gibberellins (GAs) synthesis and abiotic stress resistance in crop plants. We isolated 10 endophytes from the roots of field-grown soybean and screened their culture filtrates (CF) on the GAs biosynthesis mutant rice line - Waito-C. CF bioassay showed that endophyte GMH-1B significantly promoted the growth of Waito-C compared with controls. GMH-1B was identified as Penicillium minioluteum LHL09 on the basis of ITS regions rDNA sequence homology and phylogenetic analyses. GC/MS-SIM analysis of CF of P. minioluteum revealed the presence of bioactive $GA_4$ and $GA_7$. In endophyte-soybean plant interaction, P. minioluteum association significantly promoted growth characteristics (shoot length, shoot fresh and dry biomasses, chlorophyll content, and leaf area) and nitrogen assimilation, with and without sodium chloride (NaCl)-induced salinity (70 and 140 mM) stress, as compared with control. Field-emission scanning electron microcopy showed active colonization of endophyte with host plants before and after stress treatments. In response to salinity stress, low endogenous abscisic acid and high salicylic acid accumulation in endophyte-associated plants elucidated the stress mitigation by P. minioluteum. The endophytic fungal symbiosis of P. minioluteum also increased the daidzein and genistein contents in the soybean as compared with control plants, under salt stress. Thus, P. minioluteum ameliorated the adverse effects of abiotic salinity stress and rescued soybean plant growth by influencing biosynthesis of the plant's hormones and flavonoids.

MORPHOLOGICAL CHANGES OF DENTIN SURFACE TREATED WITH VARIOUS DENTIN SURFACE CONDITIONERS (수종(數種) 표면처리제(表面處理劑)에 의(依)한 상아질(象牙質) 표면(表面)의 형태(形態) 변화(變化)에 관(關)한 연구(硏究))

  • Cho, Jin-Ho;Choi, Ho-Young;Min, Byung-Soon;Park, Sang-Jin
    • Restorative Dentistry and Endodontics
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    • v.13 no.2
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    • pp.323-334
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    • 1988
  • The purpose of this study was to observe the effect of dentin surface conditioners on the dentin surfaces. Freshly extracted human molars were used in this study. They were stored at $4^{\circ}C$ saline solution before experiment. The crown portions of the teeth were cut in various directions by means of wet diamond point to expose dentin which include transverse, vertical oblique, horizontal and oblique cut to the long axis (Fig. 1). Each tooth was then mounted with self curing acrylic resin in brass ring to expose the flattened dentin surfaces. Final finish was accomplished by grinding the dentin specimens with wet No. 180 and No. 600 grit silicon carbide abrasive paper until a 6.0mm in diameter on a dentin surface was exposed without pulp exposure. The specimens were divided into 9 groups according to the modes of dentin treatment procedure. The following surface treatments were applied on these preparation surfaces; Group 1: unetched (control group) after finish with No. 600 silicon carbide abrasive paper. Group 2: etched with 30% phosphoric acid for 60s Group 3: etched with 10-3 solution for 60s Group 4: Cleaned with 5% NaOCl for 30s Group 5: applied Dentin Adhesit Group 6: cleaned with 5% NaOCl followed by applying the Dentin Adhesit$^{(R)}$ Group 7: applied Photo Bond on the unetched dentin followed by applying the Photo Clearfil Bright Group 8: Etched with 30% phosphoric acid followed by applying Photo Bond and Photo Clearfil Bright Group 9: etched with 10-3 solution followed by applying Photo Bond and Photo Clearfil Bright All the specimens were stored in $37^{\circ}C$ under 50% relative humidity for 24 hours before observations. The specimens in 7, 8, and 9 group, omitting the group 1 to 6, were demineralized in 10% HCl for 10s in order to observe the resin tags. All the specimens in each group were then dried at room temperature. The dried specimens were ion coated with Eiko ion coater (Eiko-engineering Co.), and observed in Hitachi S-430 Scanning electron microscope (Hitachi, Co. Tokyo) at 15KV. The following results were obtained as follows; 1. The smear layers were still remained in group 1,2,4,5, and 6. 2. There is no effect of 5% NaOCl and 30% phosphoric acid on the changes of dentin morphology 3. The dentin treated with 10-3 solution, indicating the tubules opened when the smear layer and the dental plug dissolved. 4. In case of applying the bonding agents the resin tag was not formed at the deep area of dentinal tubules, but in case of applying the Dentin Adhesit$^{(R)}$ that was not.

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Effects of one or two applications of all-in-one adhesive on microtensile bond strength to unground enamel (Unground enamel에 대한 all-in-one adhesive의 1회 또는 2회 적용이 미세인장 결합강도에 미치는 영향)

  • Son, Chang-Yong;Kim, Hyeon-Cheol;Hur, Bock;Park, Jeong-Kil
    • Restorative Dentistry and Endodontics
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    • v.31 no.6
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    • pp.445-451
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    • 2006
  • The purposes of this study were to compare the effects of one or two applications of all-in-one adhesives on microtensile bond strengths (${\mu}$TBS) to unground enamel and to investigate the morphological changes in enamel surfaces treated with these adhesives using a scanning electron microscopy (SEM). Twenty-five noncarious, unrestored human mandibular molars were used. The unground enamel surfaces were cleansed with pumice. The following adhesives were applied to lingual, mid-coronal surfaces according to manufacture's directions; Clearfil SE bond in SE group, Adper Prompt L-Pop$^{TM}$1 coat in LP1 group, 2 coats in LP2 group, Xeno$^{\R}$III1 coat in XN1 group, and 2 coats in XN2 group. After application of the adhesives, a hybrid light-activated resin composite was built up on the unground enamel. Each tooth was sectioned to make a cross-sectional area of approximately 1.0 mm$^2$ for each stick. The microtensile bond strength was determined. Each specimen was observed under SEM to examine the morphological changes. Data were analyzed with one-way ANOVA. The results of this study were as follows; 1. The microtensile bond strength values were; SE (19.77 ${\pm}$ 2.44 MPa), LP1 (13.88 ${\pm}$ 3.67 MPa), LP2 (14.50 ${\pm}$ 2.52 MPa), XN1 (14.42 ${\pm}$ 2.51 MPa) and XN2 (15.28 ${\pm}$ 2.79 MPa). SE was significantly higher than the other groups in bond strength (p < 0.05). All groups except SE were not significantly different in bond strength (p < 0.05). 2. All groups were characterized as shallow and irregular etching patterns.

Vortical Etching Characteristics of SrBi$_2$Ta$_2$O$_9$ thin Films Depending on Ar/Cl$_2$ Ratios and RF/DC Power Densities (SrBi$_2$Ta$_2$O$_9$ 박막에 있어서 Ar/C1$_2$가스의 비율 및 RF/DC Power Density의 변화에 따른 수직 식각의 특성연구)

  • 황광명;이창우;김성일;김용태;권영석;심선일
    • Journal of the Microelectronics and Packaging Society
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    • v.8 no.3
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    • pp.49-53
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    • 2001
  • Vortical etching experiments of ($SrBi_2Ta_2O_9$)/Si thin films have been performed by using the inductively coupled plasma reactive ion etching (ICP-ME) apparatus. The purposes of these experiments are to get the effective area of vertical surface. Because this technology is very important to get good qualities of ferroelectric gate structure, capacitor and the minimum parasitic effects related to the excellent performances of the FRAM (Ferroelectric Random Access Memory) device. The reacting gases were Ar and $Cl_2$gases, and various $Ar/C1_2$flow ratios were used. The etching experiments were carried out at various RF powers such as 700, 700, 500W and at various DC powers such as 200, 150, 100, 50W, respectively. The maximum etch rate of $SrBi_2Ta_2O_9$/Si thin films was 1050 A/min at the $Ar/C1_2$ gas ratio of 20/16, RF power of 700 W and DC power of 200 W. From the SEM (scanning electron microscopy) image of the SBT thin films, the wall angle was as good as about $82^{\circ}$.

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The validation of Periotest values for the evaluation of orthodontic mini-implants' stability (즉시 부하 교정용 미니임플랜트의 안정성 평가를 위한 Periotest$^{(R)}$의 유효성)

  • Cha, Jung-Yul;Yu, Hyung-Seog;Hwang, Chung-Ju
    • The korean journal of orthodontics
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    • v.40 no.3
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    • pp.167-175
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    • 2010
  • Objective: The aim of this study was to validate the Periotest values for the prediction of orthodontic mini-implants' stability. Methods: Sixty orthodontic mini-implants (7.0 mm $\times$ $\emptyset1.45$ mm; ACR, Biomaterials Korea, Seoul, Korea) were inserted into the buccal alveolar bone of 5 twelve month-old beagle dogs. Insertion torque (IT) and Periotest values (PTV) were measured at the installation procedure, and removal torque (RT) and PTV were recorded after 12 weeks of orthodontic loading. To correlate PTV with variables, the cortical bone thickness (mm) and bone mineral density (BMD) within the cortical bone and total bone area were calculated with the help of CT scanning. Results: The BMD and cortical bone thickness in mandibular alveolus were significantly higher than those of the maxilla (p < 0.05). The PTV values ranged from -3.2 to 4.8 for 12 weeks of loading showing clinically stable mini-implants. PTV at insertion was significantly correlated with IT (-0.51), bone density (-0.48), cortical bone thickness (-0.42) (p < 0.05) in the mandible, but showed no correlation in the maxilla. PTV before removal was significantly correlated with RT (-0.66) (p < 0.01) in the mandible. Conclusions: These results show that the periotest is a useful method for the evaluation of mini-implant stability, but it can only be applied to limited areas with thick cortical and high density bone such as the mandible.

Hot Corrosion Behavior of Plasma Sprayed 4 mol% Y2O3-ZrO2 Thermal Barrier Coatings with Volcanic Ash (플라즈마 용사법으로 제작된 4mol% Y2O3-ZrO2 열차폐코팅의 화산재에 의한 고온열화거동)

  • Lee, Won-Jun;Jang, Byung-Koog;Lim, Dae-Soon;Oh, Yoon-Suk;Kim, Seong-Won;Kim, Hyung-Tae;Araki, Hiroshi;Murakami, Hideyuki;Kuroda, Seiji
    • Journal of the Korean Ceramic Society
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    • v.50 no.6
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    • pp.353-358
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    • 2013
  • The hot corrosion behavior of plasma sprayed 4 mol% $Y_2O_3-ZrO_2$ (YSZ) thermal barrier coatings (TBCs) with volcanic ash is investigated. Volcanic ash that deposited on the TBCs in gas-turbine engines can attack the surface of TBCs itself as a form of corrosive melt. YSZ coating specimens with a thickness of 430-440 ${\mu}m$ are prepared using a plasma spray method. These specimens are subjected to hot corrosion environment at $1200^{\circ}C$ with five different duration time, from 10 mins to 100 h in the presence of corrosive melt from volcanic ash. The microstructure, composition, and phase analysis are performed using Field emission scanning electron microscopy, including Energy dispersive spectroscopy and X-ray diffraction. After the heat treatment, hematite ($Fe_2O_3-TiO_2$) and monoclinic YSZ phases are found in TBCs. Furthermore the interface area between the molten volcanic ash layers and YSZ coatings becomes porous with increases in the heat treatment time as the YSZ coatings dissolved into molten volcanic ash. The maximum thickness of this a porous reaction zone is 25 ${\mu}m$ after 100 h of heat treatment.