Preparation and Stability Evaluation of Docetaxel-Loaded Oral Liposome

전종란,김현미,이풍석,오의철,이마세 한국약제학회 2010 Journal of Pharmaceutical Investigation Vol.40 No.2

Docetaxel-loaded liposomes were prepared by emulsion-solvent evaporation method, then coated with chitosan at room temperature and lyophilized. This system was designed in order to improve solubility and stability of docetaxel in the GI tract for oral drug delivery. The solubilizing effect of some frequently used solubilizers and/or liposome was determined. Among the results docetaxel-loaded liposomes prepared with 0.5% TPGS as a solubilizer showed 100-fold higher solubility than docetaxel. In a stability test, mean particle size of different liposome formulations was measured by a particle size analyzer in simulated gastric fluid (SGF) and in simulated intestinal fluid (SIF). The particle size of uncoated liposomes was significantly increased compared with that of chitosan-coated liposomes in SGF, however, there was no significant difference between coated and uncoated liposome in SIF. It is evident that chitosan-coated liposomes were more stable in GI conditions. The release characteristics of docetaxel-loaded liposomes were also investigated in three buffer solutions (pH 1.2, 4.0, 6.8). Docetaxel release did not occur in pH 1.2 for 4 hrs. However, in pH 4.0 and 6.8 conditions, docetaxel was gradually released over 24 hrs as a sustained release. It seems that aggregation and precipitation of particles by electrostatic interaction might protect docetaxel from being released. In Conclusion, the results from this study show that the chitosan-coated liposomes may be useful in enhancing solubility and GI stability of docetaxel.

Formulation and Evaluation of an Alternative Triglyceride-free Propofol Microemulsion

조재평,조진철,이풍석,이마세,오의철 대한약학회 2010 Archives of Pharmacal Research Vol.33 No.9

A new triglyceride-free propofol microemulsion for intravenous injection was formulated using nonionic surfactants, poloxamers and polyethylene glycol 660 hydroxystearate. The aim of this investigation was to evaluate the formulation for storage stability, antimicrobial activity, toxicity and preclinical efficacy. The results were compared to the characteristics obtained for the most commonly used formulation of propofol (Diprivan®). The mean particle diameter of the microemulsion was less than 100 nm so that it could be readily sterilized using a 0.22 μm membrane at room temperature. The microemulsion formulation demonstrated enhanced stability compared to the marketed macroemulsion formulation. In a stress storage condition, it was physicochemically stable for at least 40 months. This new formulation showed higher antimicrobial activity, lower risk of hyperlipidemia and better tolerability than Diprivan®. In preclinical studies, the efficacy and pharmacokinetic profile of the microemulsion were similar to those of Diprivan®. Nevertheless, the administration of the microemulsion caused considerably low histamine release compared to the macroemulsion. Based on these results, the newly developed microemulsion of propofol appeared to have several advantages and, thus, could be an alternative to the fat macroemulsions of propofol.

Employing an optimized spray-drying process to produce ezetimibe tablets with an improved dissolution profile

김성엽,김종오,Biki Gupta,문철,오의철,정지헌,용철순 한국약제학회 2016 Journal of Pharmaceutical Investigation Vol.46 No.6

Ezetimibe is a low-density lipoprotein cholesterol- lowering agent with poor aqueous solubility. There is therefore a need to increase the aqueous solubility of ezetimibe in order to improve its dissolution profile, and thereby, enhance its bioavailability. The purpose of this study was to produce a solid dispersion of ezetimibe with improved physicochemical characteristics, which could be then be used to prepare ezetimibe tablets with improved dissolution characteristics. The ezetimibe solid dispersion was prepared by an optimized spray-drying process. Product characteristics, namely, yield, moisture content, solubility, and Hausner ratio, were optimized by controlling process parameters, namely, inlet temperature, pump feed rate, and solid contents, by applying the Box-Behnken design and the desirability functions approach. The physicochemical characteristics of the optimized solid dispersion were in close agreement with the predicted characteristics. The tablets formulated using the optimized solid dispersion exhibited an excellent dissolution profile, which was remarkably better than that of tablets formulated from free ezetimibe or a physical mixture of the drug and the excipients. Therefore, ezetimibe tablets with improved solubility and dissolution characteristics were produced using an optimized spray-drying technique.

Amelioration of high fat diet-induced nephropathy by cilostazol and rosuvastatin

박정현,최보현,구세광,김동현,정경아,오의철,곽미경 대한약학회 2017 Archives of Pharmacal Research Vol.40 No.3

Multiple comorbidities of metabolic disordersare associated with facilitated chronic kidney disease progression. Anti-platelet cilostazol is used for the treatmentof peripheral artery disease. In this study, we investigatedthe potential beneficial effects of cilostazol and rosuvastatinon metabolic disorder-induced renal dysfunctions. C57BL/6 mice that received high fat diet (HFD) for22 weeks and a low dose of streptozotocin (STZ, 40 mg/kg) developed albuminuria and had increased urinarycystatin C excretion, and cilostazol treatment (13 weeks)improved these markers. Histopathological changes,including glomerular mesangial expansion, tubular vacuolization,apoptosis, and lipid accumulation were amelioratedby cilostazol treatment. Tubulointerstitial fibrosisthat was indicated by the increases in collagen and transforminggrowth factor-b1 subsided by cilostazol. Renoprotectiveeffects were also observed in rosuvastatintreatedmice, and combinatorial treatment with cilostazoland rosuvastatin demonstrated enhanced ameliorativeeffects in histopathological evaluations. Notably, repressedrenal heme oxygenase-1 (Ho-1) level in HFD/STZ micewas restored in cilostazol group. Further, we demonstratedthat cilostazol enhanced Nrf2/Ho-1 signaling in culturedproximal tubular epithelial cells. Collectively, these resultssuggest the potential advantageous use of cilostazol as anadjunctive therapy with statins for the amelioration ofmetabolic disorder-associated renal injury.

Asymmetric loading of erector spinae muscles during sagittally symmetric lifting

최안렬,윤태선,이경석,민경기,황헌,이기영,오의철,문정환 대한기계학회 2009 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.23 No.1

Functional asymmetry is among the multitude of risk factors for low-back pain (LBP), the most common injury under general industrial and agricultural conditions. However, previous studies showed that normal healthy individuals exhibit some functional asymmetry, indicating that not all asymmetry causes LBP. Therefore, the threshold value that is able to discriminate between normal and pathological situations is used as critical information to predict LBP. As a preliminary study to find threshold, the purpose of this study is to quantify the magnitude of bilateral asymmetries of erector spinae muscle forces of a healthy group during sagittally symmetric lifting. Ten healthy male subjects with no history of back pathology participated in this study, which collected motion capture, force data, and electromyography signals from six infrared cameras (MCam2, Vicon), two force platforms (AMTI), and surface EMG (BME Korea). In order to quantify the magnitude of bilateral asymmetry in the trunk muscle forces, we used 3D linked segment and EMG-assisted modeling approaches, both of which were verified based on their recapitulation of previously-proposed models. The results indicated that each muscle force in the lumbar region exhibited asymmetry during the entire lifting process. In particular, the erector spinae muscle forces exhibited an approximate 24% difference between bilateral sites (p<0.05). The results of this study provided data from normal individuals by which to identify pathological situations and predict LBP incidence within general industrial and agricultural conditions.

가바펜틴을 함유한 위체류성 정제의 제조 및 용출 평가

유광희 ( Kwang Hee You ),이풍석 ( Pung Sok Lee ),오의철 ( Eui Chaul Oh ) 韓國藥劑學會 2009 Journal of Pharmaceutical Investigation Vol.39 No.4

발사르탄 이칼륨염의 신규 결정형

서성기 ( Sung Ki Seo ),김대덕 ( Dae Duk Kim ),오의철 ( Eui Chaul Oh ) 韓國藥劑學會 2009 Journal of Pharmaceutical Investigation Vol.39 No.3