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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
> Journal Vol & Issue
Journal of Pharmaceutical Investigation
Journal Basic Information
Journal DOI :
The Korean Society of Pharmaceutical Sciences and Technology
Editor in Chief :
Volume & Issues
Volume 34, Issue 6 - Dec 2004
Volume 34, Issue 5 - Oct 2004
Volume 34, Issue 4 - Aug 2004
Volume 34, Issue 3 - Jun 2004
Volume 34, Issue 2 - Apr 2004
Volume 34, Issue 1 - Feb 2004
Selecting the target year
Stability of 5-FU and Tegafur in Biological Fluids of Rats
Jang, Ji-Hyun ; Park, Jong-Kook ; Kang, Jin-Hyoung ; Chung, Suk-Jae ; Shim, Chang-Koo ; Kuh, Hyo-Jeong ;
Journal of Pharmaceutical Investigation, volume 34, issue 3, 2004, Pages 161~168
DOI : 10.4333/KPS.2004.34.3.161
5-Fluorouracil (5-FU) is an antimetabolite anticancer agent active against many types of solid tumors. Tegafur (TF), a prodrug of 5-FU, is frequently used in combination with uracil as dihydropyrimidine dehydrogenase (DPD) inhibitory fluoropyrimidine. We studied the stability of 5-FU and TF in biological fluids of rats and determined their bioavailability (BA) and excretion into bile, and urine. The drug concentrations were analyzed by an HPLC method. At room temperature, there was a 14-30% decrease in the concentration of 5-FU and TF in bile, urine, and plasma specimen at 10 and
over 240 min. No significant difference was noted among the sample types or between two different concentrations of 10 and
. The decrease in drug concentration was significantly less in samples kept on ice (6-12%) for both drugs. These data indicate that biological fluid samples containing 5-FU or TF in plasma, urine, or bile should be placed on ice during the sample collection. Following these storage guidelines, samples were collected after administration 50 mg/kg of each drug via i.v. or oral route. BA was 1.5 folds greater for TF (60%) than that of 5-FU (42%). Approximately 0.52 and 3.3% of the i.v. doses of 5-FU and TF was excreted into bile, respectively. Renal clearance of 5-FU was about 16% of its total body clearance. These results suggest that instability of 5-FU and TF in biological fluids should be considered in pharmacokinetic or pharmacogenomic studies.
Preparation and In Vitro Test of Sold Dispersion using Acyclovir and Water Soluble Polymer
Ahn, Yong-San ; Lee, Ha-Young ; Hong, Keum-Duck ; Jung, Sung-Beum ; Cho, Sun-Hang ; Rhee, John-Moon ; Lee, Hai-Bang ; Khang, Gil-Son ;
Journal of Pharmaceutical Investigation, volume 34, issue 3, 2004, Pages 169~176
DOI : 10.4333/KPS.2004.34.3.169
Acyclovir(ACV) is an important antiviral drug used extensively against infections caused by herpes viruses, especially herpes simplex and varicella zoster. Because of high crystallinity and large particle size, solubility of intact ACV is very low in water(1.3 mg/ml). The goal of this work is to enhance the solubility of ACV. To make solid dispersion, Polyethyleneglycol, Hydroxyprophylmethylcelluose and Polyvinylpyrrolidone were used as polymer carriers in this work. Polymer carriers and drug were dissolved in acetic acid. And then spray drying method and freeze drying method were used as solvent extraction. Morphology, crystallization and functional group were characterized using SEM, XRD and FT-IR. The result of in vitro test showed the sample using PVP as polymer carrier had higher dissolution rate(up to 466%) than intact ACV.
Binding of Vaccine and Poly(DL-lactide-co-glycolide) Nanoparticle Modified with Anionic Surfactant
Choi, Min-Soo ; Park, Eun-Seok ; Chi, Sang-Cheol ; Shin, Byung-Cheol ;
Journal of Pharmaceutical Investigation, volume 34, issue 3, 2004, Pages 177~183
DOI : 10.4333/KPS.2004.34.3.177
Recently, studies on intranasal mucosa delivery of influenza vaccine have been actively developed because of lack of pain and ease of administration. We studied on preparation of nanoparticle delivery system using biodegradable polymer as a poly(DL-lactide-co-glycolide) (PLGA) and their binding characteristics with vaccine. Three kinds of PLGA nanoparticles were prepared by spontaneous emulsification solvent diffusion (SESD) method using sodium dodecyl sulfate and sodium laurate as an anionic surfactant and Lutrol F68 (polyethylene glycol-block-polypropylene glycol copolymer) as a nonionic surfactant. The 5-aminofluorescein labeled vaccine was coated on the surface of nanoparticles by ionic complex. The complexes between vaccine and nanoparticles were confirmed by change of the size. After vaccine coating on the surface of anionic nanoparticles, particle size was increased from 174 to 1,040 nm. However the size of nonionic nanoparticles was not more increased than size of anionic nanoparticles. The amount of coated vaccine on the surface of PLGA nanoparticles was
with sodium dodecyl sulfate,
with sodium laurate, and
with Lutrol F68, respectively. In conclusion, prepared nanoparticles in this study is possible to use as a virus-like nanoparticles and it could be accept in the field of influenza vaccine delivery system.
Relationship Between Dissolution Patterns of Carbamazepine Tablet and Dissolution Medium Composition
Lee, Hyeon-Tae ; Kim, Jeong-Ho ; Kim, Hyun-Joo ; Sah, Hong-Kee ;
Journal of Pharmaceutical Investigation, volume 34, issue 3, 2004, Pages 185~192
DOI : 10.4333/KPS.2004.34.3.185
The objective of this study was to evaluate the effects of surfactant type and concentration upon dissolution rates of carbamazepine from an immediate-release tablet. The dissolution media used in this study were aqueous solutions containing 0.1-2% sodium lauryl sulfate, cetyltrimethylammonium bromide, or polysorbate 80. The solubility of carbamazepine in the dissolution media was determined at first. A dissolution study was then conducted by using the USP dissolution apparatus II (paddle method) with an agitation rate of 75 rpm. Aliquots of the dissolution media were taken at predetermined time intervals, and the amount of carbamazepine dissolved was measured spectrophotometrically at 285 nm. The dissolution data obtained were fitted into a biphasic exponential equation with four parameters. Excellent correlations were observed between the experimental data and the theoretical ones predicted by the equation. This equation permitted the calculation of
(the time required for dissolving 50% of carbamazepine) under various experimental conditions. Differentiation of the equation also led to the attainment of dissolution rates at dissolution time points. The addition of a surfactant to an aqueous solution led to increasing the solubility of carbamazepine by 3- to 12-folds, depending upon its type and concentration. This event also resulted in enhancing the magnitude of a sink condition during the dissolution study. As a result, the dissolution rate of carbamazepine was affected by the aqueous surfactant concentration in a proportional manner. Subsequently,
values declined rapidly, as the surfactant concentration increased. Such effects were observed in decreasing order of sodium lauryl sulfate, cetyltirmethylammonium bromide, and polysorbate 80. These results clearly demonstrated that it was possible to tailor a dissolution rate and
of carbamazepine by manipulating the type and concentration of a surfactant. Relevant information would be beneficial to setting up dissolution specifications for poorly water-soluble drug products.
Anti-wrinkle Effect of Pressure Sensitive Adhesive Hydrogel Patches Containing Ulmi Cortex Extract
Lee, Tae-Wan ; Kim, Sang-Nyun ; Jee, Ung-Kil ; Hwang, Sung-Joo ;
Journal of Pharmaceutical Investigation, volume 34, issue 3, 2004, Pages 193~199
DOI : 10.4333/KPS.2004.34.3.193
The decreasing effect of wrinkle on the pressure sensitive adhesive hydrogel patches containing ulmi cortex extract and sorbitol as the drug for anti-wrinkle were investigated. In this study, hydrogels were prepared by the crosslinking reaction of acrylic polymers and aluminum ions produced by L(+)-tartaric acid hydrolysis of the dihydroxy aluminum aminoacetates. The inhibition concentration of ulmi cortex extract on the collagenase exhibited at 0.01%. Furthermore, the moisturizing effect of hydrogel patches formulated with sorbitol was higher than that without it. In vivo animal test in hairless mouse showed that the ulmi cortex-loaded hydrogel patches had about 31.2% of anti-wrinkle effect compared to blank (before attaching the patches). Human test showed that only 33% of subjects showed the decreasing of wrinkle during 8 weeks. In conclusion, the model pressure sensitive adhesive hydrogel patches in this study would be pharmaceutically applicable for the wrinkle treatment on the facial skin.
Iontophoretic Delivery of Vitamine C 2-Phosphate
Kim, Su-Youn ; Oh, Seaung-Youl ;
Journal of Pharmaceutical Investigation, volume 34, issue 3, 2004, Pages 201~207
DOI : 10.4333/KPS.2004.34.3.201
In order to develop an optimum formulation for iontophoretic flux of vitamine C 2-phosphate (VCP), we have prepared three different hydrogels containing VCP, using carbopol, HPMC and poloxamer, and iontophoretic flux through hairless mouse skin from these hydrogels was carried out. Drug stability in phosphate buffer (PBS) solution (pH 7.4) with and without current application was studied. The effect of various factors, such as drug concentration, current density, and current profile on skin flux was also investigated. Stability study indicated that VCP in PBS (pH 7.4) solution was stable under the experimental condition, irrespective of the presence of current. Cathodal delivery increased the flux markedly, whereas the anodal and passive flux was negligible. Thus, cathodal delivery was used in all experiments. Flux increased as the drug concentration (2.5, 5.0, 7.5%) and current density
increased. Pulsed application of the current showed lower flux than constant current application. The results obtained suggest that VCP can be delivered into the skin and the amount delivered can be controlled by varying hydrogel, current density, drug concentration and current application profile.
Bioequivalence of Roxithrin
Tablet to Rulid
Tablet (Roxithromycin 150 mg)
Joung, Sun-Koung ; Lee, Yun-Young ; Cho, Tae-Seob ; Kim, Ho-Hyun ; Lee, Ye-Rie ; Lee, Kyung-Ryul ; Lee, Hee-Joo ;
Journal of Pharmaceutical Investigation, volume 34, issue 3, 2004, Pages 209~214
DOI : 10.4333/KPS.2004.34.3.209
A bioequivalence study of
tablet (Kukje Pharma. Ind. Co., Ltd.) to
tablet (Han Dok Pharma. Ind. Co., Ltd.) was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty four healthy male Korean volunteers received each medicine at the roxithromycin dose of 300 mg in a
crossover study. There was a one-week wash-out period between the doses. Plasma concentrations of roxithromycin were monitored by a high-performance liquid chromatography for over a period of 36 hours after drug administration.
(the area under the plasma concentration-time curve from time zero to 36 hr) was calculated by the linear trapezoidal rule method.
(maximum plasma drug concentration) and
(time to reach
) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed
. No significant sequence effect was found for all of the bioavailability parameters indicating that the cross-over design was properly performed. The 90% confidence intervals of the
ratio and the
were 1.00 - 1.13 and 0.98 - 1.10, respectively. These values were within the acceptable bioequivalence intervals of 0.80 - 1.25. Thus, our study demonstrated the bioequivalence of
with respect to the rate and extent of absorption.
Bioequivalence of Neuracetam Tablet to Neuromed Tablet (Oxiracetam 800 mg)
Choi, Sung-Up ; Kim, Jong-Seok ; Yoon, Mi-Kyeong ; Kim, Jung-Il ; Park, Seok ; Han, Sang-Beom ; Lee, Jae-Hwi ; Choi, Young-Wook ;
Journal of Pharmaceutical Investigation, volume 34, issue 3, 2004, Pages 215~222
DOI : 10.4333/KPS.2004.34.3.215
The purpose of the present study was designed to evaluate the bioequivalence of two oxiracetam tablets, Neuromed tablet (Korea Drug Co., reference drug) and Neuracetam tablet (Sam Jin Pharmaceutical Co., test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Release of oxiracetam from the tablet in vitro was tested using KP VIII Apparatus II method with various dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty-four healthy volunteers,
year in age and
kg in body weight, were divided into two groups and a randomized
cross-over study was performed. After oral administration of a tablet containing 800 mg of oxiracetam, blood samples were taken at predetermined time intervals and concentrations of oxiracetam in plasma were determined using HPLC-MS-MS. The dissolution profiles of two formulations were very similar at all dissolution media. In addition, pharmacokinetic parameters such as
were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed
. The results showed that the differences between two formulations based on the reference drug were 0.42%, 0.45% and -12.58% for
, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals for the log transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g.,
, respectively), indicating that Neuracetam tablet is bioequivalent to Neuromed tablet. The major pharmacokinetic parameters,
met the criteria set by KFDA for bioequivalence indicating that Neuracetam tablet is bioequivalent to Neuromed tablet.
Food-Effect Bioavailability and Fed Bioequivalence Studies
Choi, Sun-Ok ; Jung, Sung-Hee ; Um, So-Young ; Jung, Seo-Jeong ; Kim, Joo-Il ; Chung, Soo-Youn ;
Journal of Pharmaceutical Investigation, volume 34, issue 3, 2004, Pages 223~228
DOI : 10.4333/KPS.2004.34.3.223
A new medical system was started in Korea in 2000 and pharmaceutical affairs law was revised in 2001. According to the revised law, generic substitution is permitted only to the drug products which are proven to be bioequivalent to the reference listed drugs. To expand the list of bioequivalence-proven drug products and to ensure the credibility of the therapeutic equivalence of generic drug are the hot issues in Korea. Also, the KFDA has a plan to revise the pharmaceutical affairs law that bioequivalence reports of all the generic prescription drug products should be submitted to the KFDA for drug approval after July in 2004. Therefore, it is increasing the necessity to develop the bioequivalence-demonstrating methods for specific drug substances and preparations which require to conduct food-effect bioavailability or bioequivalence study. There are some differences between US and Japanese guidances of food-effect bioavailability and bioequivalence studies. In this paper, we examined the recently published US guidance about food-effect study and it will be a reference to make our own guidance about food-effect bioavailability and bioequivalence guidances in Korea.
Application of SUPAC-MR in Processing Postapproval Changes to Modified Release Sold Oral Dosage Forms
Sah, Hong-Kee ; Cho, Mi-Hyun ; Park, Sang-Ae ; Yun, Mi-Ok ; Kang, Shin-Jung ;
Journal of Pharmaceutical Investigation, volume 34, issue 3, 2004, Pages 229~254
DOI : 10.4333/KPS.2004.34.3.229
The objective of this study was to scrutinize the rationale of SUPAC-MR and its application in processing postapproval changes to modified release solid oral dosage forms. The types of postapproval changes that were primarily covered with SUPAC-MR included variations in the components and composition, the site of manufacturing, batch size, manufacturing equipment, and manufacturing process. SUPAC-MR defined levels of postapproval changes that the industry might make. Classification of such categories was based on the likelihood of risk occurrence and potential impact of changes upon the safety and efficacy of approved drug products. In most cases, the changes could be classified into 3 levels. It described what chemistry, manufacturing, and control tests should be conducted for each change level. The important tests specified in SUPAC-MR were batch release, stability, in vitro dissolution, and in vivo bioequivalence tests. It then suggested what type of a filing report should be submitted to the FDA for each change level. In general, level 1 changes could be reported in an annual report, whereas level 2 and/or 3 changes could be submitted in changes-being-effected or prior approval supplements. It could be understood that the purpose of SUPAC-MR was to maintain the safety and quality of approved modified release solid oral dosage forms undergoing certain changes. At the same time, it contributed to providing a less burdensome regulatory process with the manufacturers when they wanted to make postapproval changes. European regulatory agencies also implemented SUPAC-like regulations in handling such changes to drug products. Therefore, in this study a recommendation was made for KFDA and the Korean industry to evaluate thoroughly the usefulness of these guidances and regulations in dealing with postapproval changes to modified release solid oral dosage forms.