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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 30, Issue 4 - Dec 2000
Volume 30, Issue 3 - Sep 2000
Volume 30, Issue 2 - Jun 2000
Volume 30, Issue 1 - Mar 2000
Selecting the target year
Effect of Molecular Weights and Mixture Ratios of Polyvinylpyrrolidone on the Bioavailability of Ipriflavone Solid Dispersion
Jeong, Je-Kyo ; Khang, Gil-Son ; Rhee, John-M. ; Shin, Ho-Chul ; Lee, Hai-Bang ;
Journal of Pharmaceutical Investigation, volume 30, issue 4, 2000, Pages 235~239
Ipriflavone (3-phenyl-7-isopropoxy-4H-1-benzopyran-4-one, IP) is a well-known antiosteoporotic drug with poor bioavailability. In the previous study, we reported that the IP formulation prepared by spray-drying method with polyvinylpyrrolidone (PVP) (SIP) was very effective in improving the bioavailability of IP. In this study, we examined the effects of molecular weight and mixture ratios of PVP to IP on the systemic absorption of IP following oral administration of SIP at a dose of 50 mg/kg to rats. In the effect of molecular weight, the Cmax of spray-dried IP with PVP K30 (SIP-K30) was significantly higher than those of spray-dried IP with PVP 360 (SIP-360), spray-dried IP with PVP K90 (SIP-K90), and spray-dried IP with PVP K17 (SIP-K17) (p<0.05). The AUC of SIP-K30 was about 2, 3, and 5.5 times higher than those of SIP-360, SIP-K90, and SIP-K17, respectively. The AUC value of SIP-K30 was significantly greater than those of SIP-K17 and SIP-K90 (p<0.05) except for SIP-360. In the ratio of PVP K30 to drug, the
and the AUC value of 3 : 7 IP-PVP solid dispersion were similar to those of 5 : 5 IP-PVP and significantly higher than those of the other solid dispersions (p<0.05). It was concluded that the spray-dried IP with PVP K30 at the ratio of 3:7 (w/w) was the best formulation for improving the bioavailability of IP.
Pharmacokinetic Evaluation of Ketorolac Tromethamine Sustained-Release Pellets after Oral Administration in Rabbits
Kwak, Son-Hyok ; Hwang, Sung-Joo ; Jiang, Ge ; Nam, Kyung-Wan ; Moon, Young-Girl ; Lee, Hai-Bang ; Cho, Sun-Hang ; Yuk, Soon-Hong ; Lee, Han-Koo ; Jeong, Sang-Young ; Lee, Young-Won ;
Journal of Pharmaceutical Investigation, volume 30, issue 4, 2000, Pages 241~246
To develop a sustained-release preparation containing ketorolac tromethamine, two sustained-release pellet formulations were evaluated with a pharmacokinetic study as compared with a conventional commercial tablets (10 mg
, Roche Korea Ltd.). Two sustained-release formulations were as follows; formulation A was composed of an inner layer containing 75% of drug coated with
RS 100 membrane and an outer layer containing 25% of drug mixed with
NE30D, and formulation B was composed of only an inner layer containing 100% of drug coated with
RS 100 membrane. The dissolution test was performed for two formulations. In case of conventional tablets, 2.5 mg of drug per a dose was administered orally into male Albino rabbit (2.0-2.3 kg of body weight) 3 times at intervals of 4 hours. In case of two sustained formulations, 7.5 mg of drug was administered once orally. Blood samples were withdrawn periodically after the administration, and the blood concentration was determined by HPLC. The conventional tablets showed very high peak-trough fluctuation between administered doses, but two sustained formulations showed less fluctuation. Formulation A with the loading dose showed the time to reach minimum effective concentration (MEC) i.e. the onset time was less than 20 min, while Formulation B had more than 1 hr of the onset time. Formulation A had the more constant plasma level than formulation B. However, formulation B had a time lag, so the plasma level was less than MEC for an initial period of 1 hr. In formulation A, the plasma level was maintained within the therapeutic window
for a long period. Formulation A was thought to be an ideal sustained-release formulation for ketorolac tromethamine oral delivery system.
Development of Transdermal Delivery Systems Containing Clenbuterol
Choi, Han-Gon ; Quan, Qi-Zhe ; Jung, Si-Young ; Rhee, Jong-Dal ; Yong, Chul-Soon ;
Journal of Pharmaceutical Investigation, volume 30, issue 4, 2000, Pages 247~252
The advantages of transdermal administration are avoiding hepatic first pass effect, minimizing inter- and intra-patient variation, maintaining steady-state plasma level to provide long-term therapy from a single dose, and allowing a rapid termination of drug input. Clenbuterol, a selective
receptor stimulant, has been introduced as a potent bronchodilator for patients with bronchial asthma, chronic obstructive bronchial disease. For the development of transdermal systems containing clenbuterol, two limiting factors - long lag time and low flux - must be overcome. In this study, we attempted to select optimal formulation for preparation of clenbuterol patch using hairless mouse skin and flow-through diffusion cell. The flux of clenbuterol increased as the percent of clenbuterol dose dependently in the concentration range of 5-15%. Based on this result, we fixed the concentration of clenbuterol as 15%. The effect of various penetration enhancers on percutaneous absorption of clenbuterol through hairless mouse skin was investigated. Labrafil was the most effective enhancer, which increased the permeability of clenbuterol approximately 4-fold compared with the control without penetration enhancer. Optimal enhancer concentration was 3%. The effect of various adhesives on penetration of clenbuterol was also investigated. Among the adhesives studied, MA-31 was the most effective adhesive. Furthermore, the clenbuterol patch composed of 15% clenbuterol, 3% Labrafil and 82% MA-31, which gave most excellent penetration of drug in in vitro penetration study, maintained therapeutic plasma levels in in vivo study using S.D. rats. These studies demonstrated a good feasibility of clenbuterol administration through the intact skin using a transdermal patch, and show a possibility of the development of clenbuterol patches.
Preparation and evaluation of GFP-containing microspheres for oral vaccine delivery system
Jiang, Ge ; Park, Jong-Pil ; Kwak, Son-Hyok ; Hwang, Sung-Joo ; Maeng, Pil-Jae ;
Journal of Pharmaceutical Investigation, volume 30, issue 4, 2000, Pages 253~258
In order to design the oral vaccine delivery system, we prepared the alginate micro spheres containing GFP (green fluorescent protein) as a model drug by spray method. To optimize the preparation conditions of microspheres, we investigated the effects of various parameters including nozzle pressure, nozzle opening angle, and concentrations of sodium alginate and calcium chloride. The prepared microspheres were evaluated by measuring their sizes, loading efficiency, and morphology. The particle size of microspheres was affected by the concentration of sodium alginate and calcium chloride, nozzle pressure, and nozzle opening angle. As the concentration of sodium alginate increased, GFP loading efficiency and particles size of microsphere also increased. However, it was observed to be difficult to spray the sodium alginate solution with concentration greater than 1.5% (w/v), due to high viscosity. The pressure over
didn't affect the size of particles. As a result, the spraying method enabled us to prepare microspheres for oral vaccine delivery system. In this study, microspheres prepared with 1% (w/v) sodium alginate had greater loading efficiency and better spherical shape.
Preparation and Evaluation of Vitamine A palmitate Dry Emulsion
Lee, Jong-Pyo ; Han, Kun ;
Journal of Pharmaceutical Investigation, volume 30, issue 4, 2000, Pages 259~266
Vitamin A palmitate, an oily drug which has low chemical stability and is poorly absorbed in the intestine, was formulated into a novel powdered dosage form. This is designated as a redispersible dry emulsion by freeze-drying technique. Before preparing a dry emulsion, vitamin A palmitate oil in solid in water (O/S/W) emulsion with soybean oil and coconut oil using Aerosil 200 as an emulsion stabilizer and polyoxyethylene-polyoxypropylene-blockcopolymer (Pluronic F68) as a surfactant was prepared. The resultants of the stability tests indicated that vitamin A palmitate O/S/W emulsion was improved on increasing the oil content of the formulation. The resultant dry emulsion particles have a good stabilities and free flow properties and readily released the oily droplets to form stable emulsions on rehydration. The drug releasing property from the resultant dry emulsion particles was dependent on factors such as amount of oily carrier(soybean oil) and surfactant(Pluronic F68) formulated. Above 80% of vitamin A palmitate content was released from the dry emulsion for 1 hour. It was deduced that vitamin A palmitate dry emulsion was definitely suitable for oral administration, since small droplets of vitamine A palmitate from the dry emulsion may alter the drug absorption profile resulting in bioavailability enhancement.
Effect of Cyclodextrins on the Solubility and Stability of Aspalatone in Aqueous Solutions
Gwak, Hye-Sun ; Chun, In-Koo ;
Journal of Pharmaceutical Investigation, volume 30, issue 4, 2000, Pages 267~271
The effect of cyclodextrins on the solubility and stability of aspalatone (acetylsalicylic acid maltol ester, AM, CAS 147249-33-0), which has been recently found to have an antithrombotic effect, was investigated. The addition of
to the aqueous solution increased the solubility of AM concentration-dependently. From the phase solubility diagram, stability constants for
, -DMCD or -HPCD complexes were calculated to be 43.1, 78.3 and
. The addition of
, DMCD or HPCD to AM solution retarded the degradation rate of AM in the acidic region. However,
and HPCD rather acted as an accelerator of degradation in the neutral and alkaline regions. DMCD had a stabilizing effect at all pHs studied.
Skin Penetration and in Vivo Local Anesthetic Effect of Microemulsion-based Hydrogels Containing Lidocaine
Shin, Hyun-Woo ; Lee, Gi-Bong ; Lee, Sang-Kil ; Choi, Young-Wook ;
Journal of Pharmaceutical Investigation, volume 30, issue 4, 2000, Pages 273~278
Several topical preparations containing lidocaine, a widely used local anesthetic agent, have been developed and marketed recently for the treatment of premature ejaculation. In this study, microemulsion(ME)-based hydrogels containing lidocaine were prepared by dispersing ME to hydrogel bases such as Carbopol, sod. alginate, and sod. carboxymethylcellulose. Lidocaine-containing ME was thermodynamically stable over 6 months and had a diameter ranging from 10 to 100 nm. In vitro skin penetration of lidocaine from ME-based hydrogels followed apparent zero-order kinetics. ME-based hydrogel showed higher drug penetration during fifteen minutes after application than alcoholic hydrogel, reference preparation. Tail flick test in rat was introduced to compare in vivo local anesthetic effects of different hydrogels, and the results showed that ME-based hydrogels are superior to other hydrogels. In optical microscopy, recrystallization of lidocaine was observed within 5 min after application of reference hydrogel, but there was no change in ME-based hydrogels even after 30 minnute. These results indicated that ME-based hydrogels had some advantages in skin penetration, anesthetic effect and physical stability compared with alcoholic hydrogels. Finally it is possible to conclude that ME-based hydrogels containing lidocaine is a good topical drug delivery system for the treatment of premature ejaculation.
Quantitation of Mevinolinic Acid in Human Plasma by HPLC
Oh, Han-Suk ; Park, Dong-Young ; Seo, Sung-Hoon ; Kim, Young-Gwan ; Hong, Seon-Pyo ; Choi, Young-Wook ; Lee, Kyung-Tae ;
Journal of Pharmaceutical Investigation, volume 30, issue 4, 2000, Pages 279~282
Simple and precise high-performance liquid chromatographic (HPLC) assay was developed and validated for the determination of a HMG-CoA reductase inhibitor,
and its active metabolite (mevinolinic acid) in human plasma. The method involved solid phase extraction of mevinolinic acid and internal standard using Sep-Pak Cartridge. Samples were analyzed by reversed-phase HPLC using
column with ultraviolet detection at 238 nm. The quantitation limit of mevinolinic acid was 2 ng/ml and the calibration curve was linear over the range of 2-50 ng/ml $(r^2>0.999)$ with human plasma. The analyses of quality control samples indicated that the normal values could be predicted with an accuracy >97%. The intra- and inter-day coefficients of variation for the analyses were <10%. The average recoveries were similar (79%) for mevinolinic acid and methylmevinolinic acid. The method described has been successfully applied to the quantification of mevinolinic acid in about 1,000 human plasma samples over six-month period.
HPLC Analysis of Retinol in the Biological Fluids and Cutaneous Absorption after its Transdermal Administration
Chung, Youn-Bok ; Han, Kun ;
Journal of Pharmaceutical Investigation, volume 30, issue 4, 2000, Pages 283~288
The purpose of the present study was to investigate the topical bioavailability of retinol (vitamin A) after its transdermal administration. For this purpose, we developed the convenient HPLC method to measure the retinol concentration in the biological fluids such as plasma and skin tissues. The low detection limit was
using a gradient HPLC system of UV detection. The initial plasma concentration of retinol was about
after its i.v. bolus administration (4.32 mg/kg). The half life
in the distributive phase was 1.3 min, while retinol was slowly disappeared in the post-distributive phase. On the other hand, the maximum plasma concentration
was about 776 ng/ml after appling to rat skin at a dose of 43.2 mg/kg. Furthermore, the concentration of retinol in the skin tissues was about 600 ng/g tissue at 12 hr after its transdermal administration. In conclusion, the initial plasma concentration of retinol was comparable with the skin concentration after its cutaneous absorption, followed by being decreased with the passage of the time.
Crystal form of SKP1080
Sohn, Young-Taek ; Lee, Kyoung-Ee ;
Journal of Pharmaceutical Investigation, volume 30, issue 4, 2000, Pages 289~293
Three polymorphic modifications and one amorphous form were prepared by recrystallization under various conditions and characterized by DSC and X-ray crystallography. At
, the polymorphic modifications showed significant differences in the dissolution rate. The dissolution rate of Mod. 4, amorphous form, was faster than that of other polymorphic modifications. When all modifications were stored at 52% RH, 95% RH, and in silica gel desiccator, amorphous form was transformed at 95% humidity condition.
Determination of Erosion Rate of the Biodegradable Polymer
Park, Eun-Seok ; Chi, Sang-Cheol ;
Journal of Pharmaceutical Investigation, volume 30, issue 4, 2000, Pages 295~297
A new method to evaluate erosion of biodegradable polymer, polyanhydrides, was developed. The polymer devices were prepared with the melt-casting method and weight loss was accurately measured after agitating the devices in buffers (pH 1-9), and removing the device at selected time intervals and freeze-drying the device. The erosion rate was estimated from the plot of the weight loss(%) of device as a function of time. The freeze-drying technique used in this study is particularly useful for estimating the erosion rate of biodegradable polymer.
Guidelines of Bioequivalence Studies of Medical Products in Europe
Yoo, Tae-Moo ; Yi, Sun-Woo ; Park, In-Sook ; Suh, Soo-Kung ; Ahn, Mee-Ryung ; Choi, Hong-Suk ; Jin, Sook ; Sohn, Soo-Jung ; Yang, Ji-Sun ;
Journal of Pharmaceutical Investigation, volume 30, issue 4, 2000, Pages 299~307
Conducts and Analysis of Bioavailability & Bioequivalence Studies in Canada -Part A: Oral Dosage Formulations Used for Systemic Effects-
Yoo, Tae-Moo ; Suh, Soo-Kung ; Choi, Hong-Suk ; Park, In-Sook ; Lee, Sun-Woo ; Ahn, Mee-Ryung ; Jin, Sook ; Sohn, Soo-Jung ; Yang, Ji-Sun ;
Journal of Pharmaceutical Investigation, volume 30, issue 4, 2000, Pages 309~318