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Archives of pharmacal research : a publication of ... 25건

  1. [국내논문]   The Influence of Assay Error Weight on Gentamicin Pharmacokinetics Using the Bayesian and Nonlinear Least Square Regression Analysis in Appendicitis Patients  

    Jin, Pil-Burm (Chosun Nursing College)
    Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea v.28 no.5 ,pp. 598 - 603 , 2005 , 0253-6269 ,

    초록

    The purpose of this study was to determine the influence of weight with gentamicin assay error on the Bayesian and nonlinear least squares regression analysis in 12 Korean appen dicitis patients. Gentamicin was administered intravenously over 0.5 h every 8 h. Three specimens were collected at 48 h after the first dose from all patients at the following times, just before regularly scheduled infusion, at 0.5 h and 2 h after the end of 0.5 h infusion. Serum gentamicin levels were analyzed by fluorescence polarization immunoassay technique with TDxFLx. The standard deviation (SD) of the assay over its working range had been determined at the serum gentamicin concentrations of 0, 2, 4, 8, 12, and 16 ${\mu}g$ /mL in quadruplicate. The polynominal equation of gentamicin assay error was found to be SD ( ${\mu}g$ /mL) = 0.0246-(0.0495C)+ (0.00203C $^2$ ). There were differences in the influence of weight with gentamicin assay error on pharmacokinetic parameters of gentamicin using the nonlinear least squares regression analysis but there were no differences on the Bayesian analysis. This polynominal equation can be used to improve the precision of fitting of pharmacokinetic models to optimize the process of model simulation both for population and for individualized pharmacokinetic models. The result would be improved dosage regimens and better, safer care of patients receiving gentamicin.

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  2. [국내논문]   Effect of Solubilizing and Microemulsifying Excipients in Polyethylene Glycol 6000 Solid Dispersion on Enhanced Dissolution and Bioavailability of Ketoconazole   피인용횟수: 5

    Heo, Min-Young (National Research Laboratory for Bioavailability Control, College of Pharmacy, Kangwon National University ) , Piao, Zong-Zhu (National Research Laboratory for Bioavailability Control, College of Pharmacy, Kangwon National University ) , Kim, Tae-Wan (National Research Laboratory for Bioavailability Control, College of Pharmacy, Kangwon National University ) , Cao, Qing-Ri (National Research Laboratory for Bioavailability Control, College of Pharmacy, Kangwon National University ) , Kim, Ae-Ra (National Research Laboratory for Bioavailability Control, College of Pharmacy, Kangwon National University ) , Lee, Beom-Jin (National Research Laboratory for Bioavailability Control, College of Pharmacy, Kangwon National University)
    Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea v.28 no.5 ,pp. 604 - 611 , 2005 , 0253-6269 ,

    초록

    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.

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  3. [국내논문]   Preparation of Mucoadhesive Chitosan-Poly(Acrylic acid) Microspheres by Interpolymer Complexation and Solvent Evaporation Method II  

    Cho, Sang-Min (College of Pharmacy, Chosun University ) , Choi, Hoo-Kyun (College of Pharmacy, Chosun University, Research Center for Resistant Cells, Chosun University)
    Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea v.28 no.5 ,pp. 612 - 618 , 2005 , 0253-6269 ,

    초록

    A mucoadhesive microsphere was prepared by an interpolymer complexation and solvent evaporation method, using chitosan and poly(acrylic acid) (PAA), to prolong the gastric resid ence time of the delivery system. The Fourier transform infrared results showed that microspheres were formed by an electrostatic interaction between the carboxyl groups of the PAA and the amine groups of the chitosan. X-ray diffraction and differential scanning calorimetry analysis showed that the enrofloxacin in the chitosan-PAA microsphere was molecularly dispersed in an amorphous state. Scanning electron microscopy of the surface and the quantity of mucin attached to the microspheres indicated that chitosan-PAA microspheres had a higher affinity for mucin than those of chitosan alone. The swelling and dissolution of the chitosan-PAA microspheres were found to be dependent on the pH of the medium. The rate of enrofloxacin released from the chitosan-PAA microspheres was slower at higher pH; therefore, based on their mucoadhesive properties and morphology, the chitosan-PAA microspheres can be used as a mucoadhesive oral drug delivery system.

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  4. [국내논문]   Preparation of Controlled Release Spheronized Beads by a Simple Extrusion and Modified Spheronization Process  

    Lee, Si-Beum (National Research Lab of Pharmaceutical Technology, College of Pharmacy, Chungnam National University ) , Kim, Min-Soo (National Research Lab of Pharmaceutical Technology, College of Pharmacy, Chungnam National University ) , Jun, Seoung-Wook (National Research Lab of Pharmaceutical Technology, College of Pharmacy, Chungnam National University ) , Park, Jeong-Sook (National Research Lab of Pharmaceutical Technology, College of Pharmacy, Chungnam National University ) , Hwang, Sung-Joo (National Research Lab of Pharmaceutical Technology, College of Pharmacy, Chungnam National University)
    Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea v.28 no.5 ,pp. 619 - 625 , 2005 , 0253-6269 ,

    초록

    Beads loaded with the water-soluble drug, phenylpropanolamine HCl (PPA), were prepared using an extruder and double arm counter-rotating roller modified from a traditional pill machine. The mean diameter of the cylindrical rod-like extrudate from the ram extruder was 3 mm; that of the uncoated bead after cutting and spheronization by the modified double arm counter-rotating roller was 3.26~3.28 mm. Although the surface of the beads was moderately rough and irregular, some exhibited hump-shaped protrusions, the sphericity was acceptable (roundness 1.15) and adequate for the subsequent coating process. An increase in mean diameter of the coated beads and improvements in friability and sphericity were observed in proportion to the amount of coating material applied (ethylcellulose or Eudragit?? RS 100). It was also found that the release rate of PPA from the coated beads could be controlled by the amount and type of coating materials applied or with the incorporation of Eudragit ?? RS 100 into the core matrix. Further modifications to the double arm counter-rotating roller, including adjustment of the rotation speed and distance between the rollers, would yield smaller uncoated beads with improved roundness and surface roughness. In conclusion , the present method could be potentially applied to prepare controlled release drug delivery beads or pellet dosage forms.

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  5. [국내논문]   In Vitro and In Vivo Studies of Different Liposomes Containing Topotecan  

    Hao, Yan-Li (Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University ) , Deng, Ying-Jie (Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University ) , Chen, Yan (Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University ) , Wang, Xiu-Min (Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University ) , Zhong, Hai-Jun (Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University ) , Suo, Xu-Bin (Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University)
    Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea v.28 no.5 ,pp. 626 - 635 , 2005 , 0253-6269 ,

    초록

    Liposome as a carrier of topotecan (TPT), a promising anticancer drug, has been reported in attempt to improve the stability and antitumor activity of TPT. However, the biodistr ibution pattern of TPT liposome in vivo and PEG-modified liposome containing TPT have not been studied systemically. In this paper, the in vitro stability and in vivo biodistribution behavior of several liposomes containing TPT with different lipid compositions and PEG-modification were studied. Compared with the 'fluid' liposome (S-Lip) composed of soybean phosphatidylcholine (SPC), the 'solid' liposome (H-Lip) composed of hydrogenated soybean phosphatidylcholine HSPC decreased the leaking efficiency of TPT from liposome and enhanced the stability of liposome in fetal bovine serum (FBS) or human blood plasma (HBP). The results of biodistribution studies in S $_{180}$ tumor-bearing mice showed that liposomal encapsulation increased the concentrations of total TPT and the ratio of lactone form in plasma. Compared with free TPT, S-Lip and H-Lip resulted in 5- and 19- fold increase in the area under the curve (AUC $_{0\rightarrow\propto}$ ), respectively. PEG- modified H-Lip (H-PEG) showed 3.7-fold increase in AUC $_{0\rightarrow\propto}$ compared with H-Lip, but there was no significant increase in t $_{1/2}$ and AUC $_{0\rightarrow\propto}$ for PEG-modified S-Lip (S-PEG) compared with S-Lip. Moreover, the liposomal encapsulation changed the biodistribution behavior, and H-Lip and H-PEG dramatically increased the accumulation of TPT in tumor, and the relative tumor uptake ratios were 3.4 and 4.3 compared with free drug, respectively. There was also a marked increase in the distribution of TPT in lung when the drug was encapsulated into H-Lip and H-PEG. Moreover, H-PEG decreased the accumulation of TPT in bore marrow compared with unmodified H-Lip. All these results indicated that the membrane fluidity of liposome has an important effect on in vitro stability and in vivo biodistribution pattern of liposomes containing TPT, and PEG-modified 'solid' liposome may be an efficient carrier of TPT.

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