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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
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Journal of Pharmaceutical Investigation
Journal Basic Information
Journal DOI :
The Korean Society of Pharmaceutical Sciences and Technology
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Volume & Issues
Volume 40, Issue 6 - Dec 2010
Volume 40, Issue 5 - Oct 2010
Volume 40, Issue 4 - Aug 2010
Volume 40, Issue 3 - Jun 2010
Volume 40, Issue spc - May 2010
Volume 40, Issue 2 - Apr 2010
Volume 40, Issue 1 - Feb 2010
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Functional Implications of Transporters Under Nitrosative Stress Conditions
Yu, Kyung-Ha ; Maeng, Han-Joo ; Chung, Suk-Jae ;
Journal of Pharmaceutical Investigation, volume 40, issue 3, 2010, Pages 139~153
DOI : 10.4333/KPS.2010.40.3.139
Nitrosative stress is defined as pathophysiological conditions that are related to covalent modifications of proteins by nitration/nitrosylation by forms of nitrogen oxide (
), leading to DNA damage, ultimately, cell death. This type of stress condition appears to be associated with a number of disease states, including diabetes, inflammation and neurodegenerative diseases. Since these pathological conditions are frequently chronic in nature and, thus, require long-term treatment, changes in pharmacokinetics are likely to affect the therapy. Transporters are membrane proteins that facilitate the movement of substrates, including drugs, across plasma membranes of epithelial / endothelial cells. Since it is now increasingly evident that transporters are pharmacokinetically significant, functional alteration of transporters by this stress condition may have therapeutic relevance. In this review, experimental techniques that are used to study both in vivo and in vitro nitrosative stress are summarized and discussed, along with available literature information on the functional implication of transporters under conditions of nitrosative stress conditions. In the literature, both functional induction and impa irment were apparently present for both drug transporter families [i.e., ATP-binding cassette (ABC) and solute carrier families (SLC)]. Furthermore, a change in the function of a certain transporter appears to have temporal dependency by impairment in the early phase of nitrosative stress and induction thereafter, suggesting that the role of nitrosative stress is complex in terms of functional implications of the transporters. Although the underlying mechanisms for these alterations are not fully understood, protein nitration/nitrosylation appears to be involved in the functional impairment whereas transcript factor(s) activated by nitrosative stress may play a role, at least in part, in functional induction. Interestingly, functional induction under conditions of nitrosative stress has not been observed for SLC transporters while such impairment has been documented for both ABC and SLC transporters. Further investigations appear to be necessary to fully delineate the underlying reasons for these differences on the impact and importance of nitrosative stress conditions.
Simultaneous Determination of Valproic Acid and its Toxic Metabolites, 4-ene-VPA and 2,4-diene-VPA in Rat Plasma using a Gas Chromatographic-mass Spectrometric Method
Lee, Min-Sun ; Lee, Young-Joo ; Chung, Bong-Chul ; Jung, Byung-Hwa ;
Journal of Pharmaceutical Investigation, volume 40, issue 3, 2010, Pages 155~160
DOI : 10.4333/KPS.2010.40.3.155
A gas chromatographic-mass spectrometric (GC-MS) method was developed for the simultaneous determination of valproic acid (VPA) and its toxic metabolites, 4-ene-VPA and 2,4-diene-VPA in rat plasma. Extraction was performed in weak acidic condition (pH 5.2) to avoid degradation of 4-ene-VPA and 2,4-diene-VPA. The recoveries for 4-ene-VPA and 2,4-diene-VPA were more than 70% and that for VPA was 33-42%. R value for each compounds exceeded 0.998 in calibration curve during all the analysis. Accuracy and precision ranged from 88.3 to 113.2% and from 2.16 to 14.2%, respectively The method was successfully applied to monitor plasma concentrations of VPA, 4-ene-VPA and 2,4-diene-VPA after intravenous administration of VPA at the dose of 100 mg/kg, suggesting that these toxic metabolites may involved in the hepatotoxicity induced by VPA.
Development of Fast Dissolving Tablet Containing Herb Extract by Freeze-Drying Technique
Kim, Jae-Il ; Choi, Hoo-Kyun ;
Journal of Pharmaceutical Investigation, volume 40, issue 3, 2010, Pages 161~166
DOI : 10.4333/KPS.2010.40.3.161
A fast dissolving tablet was developed using the freeze-drying technique. Hyeonggaeyeongyotang was selected as a model oriental medicine. Formulation and processing parameters were studied to obtain freeze-dried tablet with high drug loading, good palatability, and fast disintegration time.
CLM served as both matrix former and taste masking agent. Ethanol used as co-solvent, decreased the disintegration time of tablet. Aspartame was employed to impart better taste. Drying condition was found to have a major effect in the morphology of the tablets. Freeze-drying process was optimized to decrease the processing time and improve the appearance of the tablets.
Enhanced Controlled Transdermal Delivery of Hydrochlorothiazide from an Ethylene-vinyl Acetate Matrix
Kim, Dal-Keun ; Park, Jung-Chan ; Chang, Ik-Hyun ; Kang, Chung ; Ryu, Sang-Rok ; Shin, Sang-Chul ;
Journal of Pharmaceutical Investigation, volume 40, issue 3, 2010, Pages 167~173
DOI : 10.4333/KPS.2010.40.3.167
Repeated oral administration of hydrochlorothiazide, a loop diuretic, due to transient high blood levels, may cause adverse effects such as gastric disturbance, nausea, high blood sugar, and hyper lipidemia. Transdermal administration could avoid some of these systemic side effects and gastric disorders. We have developed a matrix using ethylene-vinyl acetate (EVA), a heat-processible and flexible material, for transdermal delivery of hydrochlorothiazide. Drug solubility was highest at 40% PEG-400 volume fraction. Drug release increased as concentration increased with a linear relationship between the release rate and the square root of loading dose. Increasing temperature increased drug release from the EVA matrix. The activation energy, measured from the slope of log P versus 1000/T, was 11.9 kcal/mol for a 2.5% loading dose from EVA matrix. Diethyl phthalate had the highest plasticizing effects on the release of hydrochlorothiazide. To increase the skin permeation of hydrochlorothiazide from the EVA matrix, enhancers such as the saturated fatty acids, the unsaturated fatty acids, and the non-ionic surfactants were added to the EVA matrix, and skin permeation was evaluated using a modified Keshary-Chien diffusion cell fitted with intact excised rat skin. Polyoxyethylene 23-lauryl ether showed the highest enhancing effects. In conclusion, transdermal delivery of hydrochlorothiazide could be improved from an EVA matrix containing plasticizer and permeation enhancer.
Preparation and Evaluation of a 4-Branched Polyethylene Glycol Derivative Modified with Exendin-4 and Stearylamine for Extended Hypoglycemic Action
Kim, In-Soo ; Ma, Kyung-Wan ; Bae, Sung-Ho ; Yoon, Jeong-Hyun ; Oh, Kyung-Taek ; Lee, Eun-Seong ; Lee, Don-Haeng ; Lee, Kang-Choon ; Youn, Yu-Seok ;
Journal of Pharmaceutical Investigation, volume 40, issue 3, 2010, Pages 175~180
DOI : 10.4333/KPS.2010.40.3.175
Albumin-modification has been viewed as one of the most effective ways of extending the short in vivo lifetimes of peptide drugs by delaying glomerular filtration. In this study, we describe a new type 2 anti-diabetic exendin-4 (Ex4) peptide derivative with significant binding ability to human serum albumin (HSA). This exendin-4 derivative consists of a 4-branched polyethylene glycol
(Mw: 20 kDa) modified with three stearylamines (
) and one exendin-4 on its branches. PEG and stearylamine were selected to provide functionality to increase molecular size and bind to albumin, respectively. This derivative (
-Ex4) was shown to have larger molecular size (Ca. 152 kDa) than actual (25.0 kDa) when subjected to size-exclusion chromatography, and the fluorescein-tagged
-Ex4 displayed significant binding to the HSA-immobilized Sepharose CL-4B resin using confocal laser scanning microscopy. Furthermore,
-Ex4 was found to have acceptable anti-hyperglycemic efficacy via three consecutive oral glucose tolerance testings (OGTT) in fasted type 2 diabetic db/db mice. The
-Ex4 at a 50 nmol/kg dose was 2-fold greater than that (
) of native exendin-4 in non-fasted db/db mice. Especially, the blood glucose levels in the mice group treated with
-Ex4 did not rebound to ~150 mg/dL until 24 h after the injection, which obviously shows the extended hypoglycemia. We believe that this derivative has great pharmaceutical potential as a novel long-acting type 2 anti-diabetic injection treatment.
Improved Dissolution of Poorly Water Soluble TD49, a Novel Algicidal Agent, via the Preparation of Solid Dispersion
Lee, Hyoung-Kyu ; Cho, Hoon ; Han, Hyo-Kyung ;
Journal of Pharmaceutical Investigation, volume 40, issue 3, 2010, Pages 181~185
DOI : 10.4333/KPS.2010.40.3.181
The objective of this study was to improve the extent of drug release as well as the dissolution rate of TD49, a novel algicidal agent, via the preparation of solid dispersion (SD). Among the various carriers tested,
HS15 was most effective to enhance the solubility of TD49. Subsequently, SDs of TD49 were prepared by using
HS15 and their solubility, dissolution characteristics and drug crystallinity were examined at various drug-carrier ratios. Solubili ty of TD49 was increased significantly in accordance with increasing the ratio of
HS15 in SDs. Compared to untreated powders and physical mixtures (PMs), SDs facilitated the faster and greater extent of drug release in water. Particularly, SD having the drug-carrier ratio of 1:20 exhibited approximately 90% of drug release within 1 hr. Differential scanning calorimetry (DSC) thermograms and X-ray diffraction (XRD) patterns suggested that SDs might enhance the dissolution of TD49 by changing the drug crystallinity to an amorphous form in addition to the increased solubilization of drug in the presence of
HS15. In conclusion, SD using
HS15 appeared to be effective to improve the extent of drug release and the dissolution rate of poorly water soluble TD49.
The Effects of Storage Conditions on the Stability of Porcine Placenta Extract-loaded Liposome Formulations
Noh, Sang-Myoung ; Park, Da-Eui ; Im, Sae-Won ; Kim, Sun-Il ; Kim, Young-Bong ; Oh, Yu-Kyoung ;
Journal of Pharmaceutical Investigation, volume 40, issue 3, 2010, Pages 187~192
DOI : 10.4333/KPS.2010.40.3.187
We aimed to evaluate the effect of temperature, pH, and light conditions on the stability of porcine placental extract (PPE)-loaded liposomes with different surface charges. The size distribution profiles and in vitro release patterns were investigated by dynamic light scattering method and spectrophotometry. The stability of PPE-loaded liposomes was affected by the surface charges of the liposomes. As compared to neutral and anionic liposomes, cationic liposome formulations showed significantly lower physical stability. At the test storage conditions of different temperatures and pHs, the mean sizes of cationic PPE-loaded liposomes substantially increased. In contrast, neutral and anionic liposomes did not reveal significant changes in mean sizes upon various storage conditions. The neutral and anionic liposomes showed no significant differences in the release profiles of PPE after storage at various temperatures and pHs. Our results indicate that anionic and neutral liposome compositions might be more suitable for the formulations of PPE providing the higher stability.
Effect of HPLC Analytical Procedure upon Determining Drug Content in PLGA Microspheres
Heo, Sun-Ju ; Lee, Hong-Hwa ; Lee, Min-Jung ; Sah, Hong-Kee ;
Journal of Pharmaceutical Investigation, volume 40, issue 3, 2010, Pages 193~200
DOI : 10.4333/KPS.2010.40.3.193
The objective of this study was to investigate the effects of sample preparation, HPLC conditions and peak measurement methods upon determining progesterone content of poly-d,l-lactide-co-glycolide microspheres. A series of the microspheres with different formulations was first prepared. To determine their actual drug contents, the microspheres were dissolved in tetrahydrofuran and diluted with various amounts of methanol to precipitate the polymer. After removal of polymeric precipitates, the filtrates were subject to HPLC analysis under versatile experimental conditions. Interestingly, the composition of a sample solution (e.g., the ratio of methanol to tetrahydrofuran) affected the magnitudes of both peak fronting and peak broadening of progesterone. Its peak became broader and more asymmetrical at lower methanol:tetrahydrofuran ratios. Furthermore, its peak height was influenced by the proportion of tetrahydrofuran in a sample solution. Such problems encountered with tetrahydrofuran were exacerbated when a larger volume of the sample solution was injected onto an analytical column. Under our experimental conditions a peak area measurement provided more accurate and reliable determination of progesterone content in various microspheres than a peak height determination. Optimizing the composition of a sample solution, HPLC chromatographic conditions and peak analysis methods was a prerequisite to an accurate determination of progesterone encapsulated within microspheres.