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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
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Volume & Issues
Volume 32, Issue 4 - Dec 2002
Volume 32, Issue 3 - Sep 2002
Volume 32, Issue 2 - Jun 2002
Volume 32, Issue 1 - Mar 2002
Selecting the target year
Current Status of Gene Therapy as a New Drug Delivery System
Bae, Yun-Sung ; Cho, Jung-Yoon ; Ji, Sang-Mi ; Lee, Young-Joo ;
Journal of Pharmaceutical Investigation, volume 32, issue 3, 2002, Pages 153~159
DOI : 10.4333/KPS.2002.32.3.153
Gene therapy is fundamentally a sophisticated drug delivery technology to cure a disease by the transfer of genetic material to modify living cells. In other words, the gene is used as a therapeutic drug much like a chemical compound is employed in chemotherapy. Currently almost 600 clinical trials are underway worldwide since the first clinical trials carried out in 1990 to treat adenosine deaminase deficiency using retroviral vectors. Despite the great progress still is there no gene therapy product being approved as a new drug. This is partly due to a lack of an ideal gene delivery system that is safe and can provide stable, optimal level production of the therapeutic proteins in the cell. This review covers the current status of several different biological and physico-chemical agents that are being developed as gene delivery vehicles. Although gene therapy promises great hopes toward the cure of a broad spectrum of genetic and acquired diseases, the success of gene therapy heavily asks for the development of vector systems for safe and efficient application in humans.
In Vitro and In Vivo Studies of Topical Delivery System of Gentisic Acid in Hairless Mice
Bian, Shengjie ; Zheng, Junmin ; Kim, Jung-Sun ; Choi, Myeong-Jun ; Chung, Ho-Kwon ; Lee, Chi-Ho ; Kim, Dae-Duk ;
Journal of Pharmaceutical Investigation, volume 32, issue 3, 2002, Pages 161~164
DOI : 10.4333/KPS.2002.32.3.161
Gentisic acid is a skin-whitening agent which inhibits the tyrosinase activity, an essential enzyme in the process of biological synthesis of melanin. Since melanin is synthesized in melanocytes located between the viable epidermis and dermis layer, drug amount delivered into the epidermis/dermis layer can provide valuable information for the biological effect of skin-whitening agents. The purpose of this study was to prepare the gentisic acid patches with 2% dodecylamine as enhancer, and to observe the in vitro skin permeation and in vivo skin deposition of gentisic acid. Gentisic acid in DuroTak 87-2510 patch formulation permeated across hairless mouse skin at the rate of
. In vivo study showed that the gentisic acid amount in both the stratum corneum and the viable epidermis/dermis increased with the increase of application time. The amount of gentisic acid in the stratum corneum was higher than that in the epidermis/dermis layer, and was expected to provide a reservoir effect even after removing the patches. Thus, the patch formulation seems to be useful for the topical delivery of skin-whitening agent into the epidermis/dermis layer, the target site.
Injectable Gel Type Formulation of Hydrated Egg Phosphatidylcholine and Hyaluronate for Local Drug Delivery
Kim, Sang-Gyun ; Chung, Hesson ; Lee, In-Hyun ; Kang, Seung-Back ; Kwon, Ick-Chan ; Sung, Ha-Chin ; Jeong, Seo-Young ;
Journal of Pharmaceutical Investigation, volume 32, issue 3, 2002, Pages 165~172
DOI : 10.4333/KPS.2002.32.3.165
Injectable gel composed of egg phosphatidylcholine (egg PC), hyaluronate (HA) and water was formulated for local drug delivery. The lamellar liquid crystalline structure of the egg PC/water system did not change by adding HA in the formulation. However, egg PC/HA/water gel was more resistant to erosion than the egg PC/water gel. The egg PC/HA/water and egg PC/water gels containing model drugs, tetracycline and sudan IV were prepared to perform in vitro and in vivo drug release experiments. In vitro release of tetracycline was sustained in the gel type formulations. The release rate of hydrophobic sudan IV was extremely slow. More than 99% of sudan IV remained inside the gel after 5 days. In vivo release of drugs from the air pouch model in Balb/c mice shows that lipophilic sudan IV remained for more than 10 days whereas tetracycline remained for 1 day in the pouch. The compatibility of the gels was also examined by histopathology. The gels did not cause any adverse inflammatory effect in the air pouch.
Preparation and Characterization of Solid Dispersion of Ipriflavone with Polyvinylpyrrolidone
Jeong, Je-Kyo ; Kim, Jung-Hoon ; Khang, Gil-Son ; Rhee, John M. ; Lee, Hai-Bang ;
Journal of Pharmaceutical Investigation, volume 32, issue 3, 2002, Pages 173~179
DOI : 10.4333/KPS.2002.32.3.173
Solid dispersions of ipriflavone with PVP were prepared by a spray-drying method in order to improve the bioavailability. They were measured with scanning electron microscopy, differential scanning calorimetry, x-ray powder diffraction, and Fourier transform infrared spectroscopy to evaluate the physicochemical interaction between ipriflavone and PVP and study the correlation between these physicochemical characteristics and bioavailability. Ipriflavone exhibited crystallinity, whereas PVP was almost amorphous. The area of the endotherm
of freezer milled ipriflavone, freezer milled ipriflavone physically mixed with freezer milled PVP, and physically mixed ipriflavone with PVP was almost the same, whereas
of the solid dispersed ipriflavone with PVP was much smaller than that of the other preparation types. Also, the crystallinity and the crystal size of ipriflavone in the solid dispersed ipriflavone with PVP were much smaller than those of the other preparation types. From the in vivo test, the AUC of the solid dispersed ipriflavone with PVP was approximately 10 times higher than that of the physically mixed ipriflavone with PVP. The solid dispersion using the spray-drying method with a water-soluble polymer, PVP, may be effective for the improvement of the bioavailability.
Encapsulation of Plasmid DNA in Erythrocyte Ghosts
Byun, Hyang-Min ; Park, Sang-Eun ; Kim, Jung-Mogg ; Ko, Jung-Jae ; Oh, Yu-Kyoung ;
Journal of Pharmaceutical Investigation, volume 32, issue 3, 2002, Pages 181~184
DOI : 10.4333/KPS.2002.32.3.181
This study reports the encapsulation of plasmid DNA in erythrocyte ghosts. The plasmid DNA was encapsulated into erythrocyte ghosts using three methods; osmotic shock, electroporation in isotonic medium, and e1ectroporation in hypotonic medium. Of three methods, electroporation in hypotonic medium resulted in the highest encapsulation efficiency of plasmid DNA. The morphology of erythrocyte ghosts prepared by electroporation in hypotonic medium was similar to that by osmotic shock alone. The circulation time of plasmid DNA in mice was prolonged by administration in erythrocyte ghost-encapsulated forms. These results indicated the potential of erythrocyte ghosts for biocompative nonviral delivery system of therapeutic genes for hematological diseases.
Improvement of Dissolution rate of Felodipine Using Solid Dispersion and its Sustained Release Oral Dosage Form
Gil, Young-Sig ; Hong, Seok-Cheon ; Yu, Chang-Hun ; Shin, Hyun-Jong ; Kim, Jong-Sung ;
Journal of Pharmaceutical Investigation, volume 32, issue 3, 2002, Pages 185~190
DOI : 10.4333/KPS.2002.32.3.185
To improve the solubility of poorly water-soluble drug and to develop a sustained release tablets, the need for the technique, the formation of solid dispersion with polymeric materials that can potentially enhance the dissolution rate and extent of drug absorption was considered in this study. The 1:1, 1:4, and 1:5 solid dispersions were prepared by spray drying method using PVP K30, ethanol and methylene chloride. The dissolution test was carried out at in phosphate buffer solution at
in 100 rpm. Solid dispersed drugs were examined using differential scanning calorimetry and scanning electron microscopy, wherein it was found that felodipine is amorphous in the PVP K30 solid dispersion. Felodifine SR tablets were prepared by direct compressing the powder mixture composed of solid dispersed felodipine, lactose, Eudragit and magnesium stearate using a single punch press. In order to develop a sustained-release preparation containing solid dispersed felodipine, a comparative dissolution study was done using commercially existing product as control. The dissolution rate of intact felodipine, solid dispersed felodipine and its physical mixture, respectively, were compared by the dissolution rates for 30 minutes. The dissolution rates of felodipine for 30 minutes from 1:1, 1:4, 1:5 PVP K30 solid dispersion were 70%, 78% and 90%. However, dissolution rate offelodipine from the physical mixture was 5% of drug for 30 minutes. Our developed product Felodipine SR Tablet showed dissolution of 17%, 50% and 89% for 1, 4, and 7 hours. This designed oral delivery system is easy to manufacture, and drug releases behavior is highly reproducible and offers advantages over the existing commercial product. The dissolution rate of felodipine was significantly enhanced, following the formation of solid dispersion. The solid dispersion technique with water-soluble polymer could be used to develop a solid dispersed felodipine SR tablet.
Dissolution Profiles of Solid Dispersions Containing Poorly Water-Soluble Drugs and Solubilizing Compositions
Kim, Tae-Wan ; Choi, Choon-Young ; Cao, Qing-Ri ; Kwon, Kyoung-Ae ; Lee, Beom-Jin ;
Journal of Pharmaceutical Investigation, volume 32, issue 3, 2002, Pages 191~197
DOI : 10.4333/KPS.2002.32.3.191
Polymer based physical mixtures or solid dispersions containing solubilizing compositions[OA, tween80 and SLS] were prepared using a spray-dryer. Lovastatin(LOS), simvastatin(SIMS), aceclofenac(AFC) and cisapride(CSP) were selected as poorly water-soluble drugs. Dextrin, poly(vinylalcohol) (PVA), poly(vinylpyrrolidone)(PVP) and polyethylene glycol(PEG) were chosen as solubilizing carriers for solid dispersions. The solid dispersions containing solubilizing compositions without drug were prepared without using organic solvents or tedious changes of formulation compositions. This system could be used to quickly screen the dissolution profiles of poorly water-soluble drugs by simply mixing with drugs thereafter. In case of solid dispersion containing drug, organic solvent systems could be used to solubilize model drugs. The dissolution rates of the drugs were higher when mixed with drug and solid dispersions containing solubilizing compositions. However, solid dispersions of LOS, AFC, and CSP simultaneously containing drug and solubilizing compositions in organic solvent systems were more useful than physical mixtures of drug and solid dispersions without drug except SIMS. Based on solubilizing capability of polymer based physical mixtures in gelatin hard capsules, optimal solid dispersion system of poorly water-soluble drugs could be formulated. However, it should be noted that dissolution rate of poorly water-soluble drugs were highly dependent on drug properties, solubilizing compositions and polymeric carriers.
Sustained Release Injectable of Recombinant Bovine Somatotropin in Biodegradable Poly(D,L-lactide-co-glyceride) Microspheres
Jeon, Hong-Ryeol ; Lee, Bong-Sang ; Kown, Do-W ; Yoon, Mi-Kyoung ; Jeon, Hyun-Joo ; Shin, Taek-Hwan ; Choi, Young-Wook ;
Journal of Pharmaceutical Investigation, volume 32, issue 3, 2002, Pages 199~207
DOI : 10.4333/KPS.2002.32.3.199
In order to develop a sustained release formulation of bovine somatotropin (BST), which has been used to increase the body weight of oxen or the milk production of dairy cows, poly(D,L-lactide-co-glyceride)(PLGA) microspheres were made by W/O/W multiple emulsification method and solvent extraction method. Physical properties including particle size, drug entrapment, drug release, protein denaturation, and in vivo body weight increase in rats were characterized. The size of the microspheres was increased as the molecular weight of PLGA increased. When Span 65 and stearic acid during preparation were added, the size was decreased but the amount of surface protein was increased, resulting in a high loading efficiency, with fast release of BST from the microspheres. Aggregation or fragmentation of BST by SDS-PAGE during microsphere preparation and drug release study was not observed. Body weight of Sprague-Dawley's male rats was significantly increased after subcutaneous administrations of BST-loaded PLGA microspheres. There was a good correlation between in vivo weight gain and in vitro release rate of microspheres. PLGA microspheres with a high surface protein ratio could be a good candidate for the sustained delivery of BST.
Drug Interaction between Cimetidine and Diltiazem in Rabbits
Lee, Jin-Hwan ; Choi, Jun-Shik ; Moon, Young-Min ;
Journal of Pharmaceutical Investigation, volume 32, issue 3, 2002, Pages 209~213
DOI : 10.4333/KPS.2002.32.3.209
Diltiazem inhibits calcium channels and Iεads to vascular smooth muscle rεlaxation and negative inotropic and chronotropic effects in the hεart. Diltiazem is almost completely absorbεd after oral administration, but its extent of absolute oral bioavailability is reduced because of considerable first-pass hepatic metabolism. Diltiazem is able to dilate renal vasculature and can increase the glomerular filtration rate and renal sodium excretion. The purpose of this study was to report the pharmacokinetic changes of diltiazem after oral administration of diltiazem, 20 mg/kg, in rabbits coadministered with cimetidine, 20 mg/kg and pretreated twice per day for 3 days at cimetidine dose of 20 mg/kg. The area under the plasma concentration-time curve (AUC) of diltiazem was significantly higher in rabbits pretreated with cimetidine than that in control rabbits (p<0.01), showing about 149% increased relative bioavailability. The peak plasma concentration
and elimination half-life of diltiazem were increased significantly (p<0.05) in rabbits pretreated with cimetidine compared with those in control rabbits. This findings could be due to significant reduction of elimination rate constant by pretreated with cimetidine. The effects of cimetidine on the pharmacokinetics of oral diltiazem were more considerable in rabbits pretreated with cimetidine compared with those in control rabbits. The results suggest that the dosage of diltiazem should be adjusted when the drug would be co-administerεd chronically with cimetidine in a clinical situation.
Bioequivalence of Broadcef Capsule to Cefradine Yuhan Capsule (Cephradine 500 mg)
Cho, Hea-Young ; Lee, Suk ; Kang, Hyun-Ah ; Oh, In-Joon ; Lim, Dong-Koo ; Moon, Jai-Dong ; Lee, Yong-Bok ;
Journal of Pharmaceutical Investigation, volume 32, issue 3, 2002, Pages 215~221
DOI : 10.4333/KPS.2002.32.3.215
Cephradine is a first generation cephalosporin and has broad spectrum antibacterial activity against gram-positive and gram-negative microorganisms, through inhibition of bacterial cell wall synthesis. Cephradine is useful for treatment of infections of the urinary and respiratory tract, skin and soft tissues. The purpose of the present study was to evaluate the bioequivalence of two cephradine capsules, Cefradine Yuhan (YuHan Corporation) and Broadcef (Ilsung Pharmaceuticals Co. Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The cephradine release from the two cephradine capsules in vitro was tested using KP VII Apparatus II method with various different kinds of dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty normal male volunteers,
years in age and
in body weight, were divided into two groups and a randomized
cross-over study was employed. After one capsule containing 500 mg as cephradine was orally administered, blood was taken at predetermined time intervals and the concentrations of cephradine in serum were determined using HPLC method with UV detector. The dissolution profiles of two cephradine capsules were very similar at all dissolution media. Besides, the 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 in
between two capsules based on the Cefradine Yuhan were -2.87%, -0.96% and -4.85%, respectively. There were no sequence effects between two capsules in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of 1og(0.8) to log(1.25)
. The 90% confidence interval using untransformed data was within
. All parameters met the criteria of KFDA guideline for bioequivalence, indicating that Broadcef capsule is bioequivalent to Cefradine Yuhan capsule.
Bioequivalence of Glycomin Tablet to Glucophage Tablet (Metformin HCl 500 mg)
Cho, Hea-Young ; Moon, Jai-Dong ; Lee, Yong-Bok ;
Journal of Pharmaceutical Investigation, volume 32, issue 3, 2002, Pages 223~229
DOI : 10.4333/KPS.2002.32.3.223
Metformin is an oral antihyperglycemic agent used in the therapy of noninsulin-dependent diabetes mellitus and does not cause hypoglycemia at the therapeutic dose. Its mechanism of action may involve an increased binding of insulin to its receptors and glucose uptake at the post-receptor level. The purpose of the present study was to evaluate the bioequivalence of two metformin tablets, Glucophage (Daewoong Pharmaceutical Co., Ltd.) and Glycomin (Ilsung Pharmaceuticals Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The metformin release from the two metformin tablets in vitro was tested using KP VII Apparatus II method with various dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty four normal male volunteers,
years in age and
in body weight, were divided into two groups with a randomized
cross-over study. After one tablet containing 500 mg as metformin was orally administered, blood was taken at predetermined time intervals and the concentrations of metformin in serum were determined using HPLC with UV detector. Besides, the dissolution profiles of two metformin tablets were very similar at 떠1 dissolution media. The pharmacokinetic parameters such as
were calculated. The ANOVA test was performed for the statistical analysis of the logarithmically transformed
. The results showed that the differences in
between two tablets based on the Glucophage were 0.09%, 6.09% and -8.22%, respectively. There were no sequence effects between two tablets in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(1.25)
, indicating that Glycomin tablet is bioequivalent to Glucophage tablet.