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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
Editor in Chief :
Volume & Issues
Volume 27, Issue 4 - Dec 1997
Volume 27, Issue 3 - Sep 1997
Volume 27, Issue 2 - Jun 1997
Volume 27, Issue 1 - Mar 1997
Selecting the target year
Hepatic Uptake and Stability of Acyclovir-Asialofetuin Conjugate
Son, Sung-Ho ; Huh, Keun ; Lee, Young-Dae ; Oh, Doo-Man ; Yong, Chul-Soon ;
Journal of Pharmaceutical Investigation, volume 27, issue 1, 1997, Pages 1~10
For the purpose of improving the chemotherapeutic index of acyclovir(ACV), it was conjugated with asialofetuin(AF), which has been reported to enter into hepatocytes. When
acyclovir in itself or its conjugate were administered to rats, the latter was taken up more selectively by the liver than any other tissues. The stability of ACVMP-AF conjugate in phosphate buffer (pH 5.0) and rat liver homogenate showed a pseudo-first order profile. ACVMP-AF, however, was relatively stable in pH7.4 phosphate buffer and rat plasma. The conjugate was added to the isolated rat hepatocyte and cellular uptake was monitored by scintillation counting for up to 6 hours at
. Hepatocytes incubated with the conjugate exhibited radioactivities significantly enhanced over control levels dose-dependently, i.e., a 3-40 fold increase in radioactivities was observed over controls at the conjugate concentrations of
. The AUQ in the liver, kidney, spleen, intestine and lung was higher in treatment with ACVMP-AF than that in treatment with ACV. In treatment with ACVMP-AF, the weighted-average overall drug targeting efficiency(Te) for the liver was higher than in treatment with ACV(57.00 vs 13.31 %), and the weighted-average tissue exposure(Re) was 5.03 for the liver. These results indicated that ACVMP-AF conjugate was rapidly taken up by hepatocytes and could be an efficient and selective hepatic targeting system.
Comparison of Diclofenac Sodium and Diclofenac
Complexation on Gastric Mucosal Injury in Rats
Park, Jae-Hoon ; Kim, Jong-Hwan ; Kim, Joo-Il ; Kim, Seung-Jo ; Seo, Seong-Hoon ; Lee, Kyung-Tae ;
Journal of Pharmaceutical Investigation, volume 27, issue 1, 1997, Pages 11~14
This laboratory has recently reported the solubility and in vivo absorption enhancement of diclofenac sodium by
complexation. The acute gastroduodenal mucosa injury provoked by administration of 34 mg/kg and 68 mg/kg of a diclofenac sodium (DS) and equivalent dose of new formulation [diclofenac sodium-beta-cyclodextrin complexation
] was evaluated and compared. Microscopic examinations, performed after 18-hrs treatment, demonstrated that
was less gastrolesive than DS. The drop in gastrophy after a single dose of the assigned drug was considerably greater for DS than for
, which registered similar values to control. Since gastrophy is an expression of the anatomy-functional integrity of the gastric barrier, the results indicate that
exerts less direct acute damage on the gastric mucosa. Therefore, when administered short-term,
appears to be less gastrolesive than the standard DS formulation.
Transvaginal Delivery of Luteinizing Hormone-Releasing Hormone Using Bioadhesive Hydrogel
Han, Kun ; Park, Hee-Beom ; Park, Jeong-Sook ; Chung, Youn-Bok ;
Journal of Pharmaceutical Investigation, volume 27, issue 1, 1997, Pages 15~22
The mucosal route of administration(nasal, buccal, conjunctival and vaginal) has recently been considered as an alternative to parenteral delivery for many peptide drugs because enzymatic degradation of these agents may be partly avoided. The objective of these study was to establish the optimal mucosal administration dosage form of
, based on presystemic metabolism. We reported previously the peptidase inhibition effect of medium chain fatty acid salts(sodium caprylate, soadium caprate and sodium laurate), EDTA and STDHF on the proteolysis of
in rabbit mucosal homgenates. We also reported that EDTA, STDHF and sodium laurate markedly increased the potency of
solution applied vaginally. In the present study, by administration of polycarbophil hydrogel containing LHRH the ovulation inducing activity was 3.3 times greater than solution. These results indicate not only peptidase inhibitor but also polycarbophil hydrogel significantly improved the absorption of this drug. The results of this study would provide the feasibility as a rational dosage form for improving bioavailability and self administration of this hydrogel by the vaginal application.
Effect of L-arginine on the Stability of Omeprazole
Lee, Eun-Jin ; Han, Kyung-Doo ; Shin, Hee-Jong ; Kim, Jung-Woo ; Kim, Chong-Kook ;
Journal of Pharmaceutical Investigation, volume 27, issue 1, 1997, Pages 23~27
To investigate the effect of L-arginine as stabilizing agent for omeprazole, the degradation rate constant of omeprazole in aqueous solution was determined at 30, 40 and
with various ratios of L-arginine to omeprazole. The pH of omeprazole solutions was also determined. As the amount of L-arginine increased, the pH of omeprazole solution also increased, and the solution appeared to be more stable. The omeprazole in aqueous solution could be stabilized by more than 15:1 molar ratio of L-arginine to omeprazole. The stability of omeprazole in commercial products using L-arginine or sodium phosphate dibasic as stabilizing agent was investigated. Among the commercial products, the omeprazole product prepared with L-arginine (molar ratio of L-arginine to omeprazole, 20:1) was most stable.
Preparation and Bioavailability of Oriental Medicine Containing Baicalin (III) : Preparation of Inclusion Complex and Bioavailability of Coprecipitated Product of Scutellariae Radix and Coptidis Rhizoma
Yang, Jae-Heon ; Shin, Sang-Chul ; Yoo, Hee-Doo ;
Journal of Pharmaceutical Investigation, volume 27, issue 1, 1997, Pages 29~38
Precipitation was formed during the preparation of decoction from a mixture of Scutellariae Radix and Coptidis Rhizoma. Baicalin and berberine were identified in this coprecipitated product (CPP) and these components were the active ingredients of two herbal medicine. We extracted respectively crude baicalin and berberine in Scutellariae Radix and Coptidis Rhizoma and prepared coprecipitate of crude baicalin-berberine. To increase the stability and bioavailability of coprecipitate of crude baicalin-berberine(CBB), which is slightly soluble drug, its inclusion complex was prepared and studied in this experiment. Inclusion complex of CBB with
was prepared by freeze drying method and its characteristics were ascertained by means of solubility test, differential thermal analysis(DTA) and scanning electron microscope(SEM). The type of
is classified as
on phase solubility diagram, and the stoichiometric ratio of CBB(baicalin in CBB) :
complex is 1:1 and formation constant is 151
. The solubility, dissolution, in situ absorption and serum concentration of
were significantly increased when compared to CBB. Therefore enhanced bioavailability of CBB by inclusion complexation with
might be useful for dosage form design of active ingredients of two herbal medicine.
Adsorption of Nicotinic Acid on the Porous Powders
Shin, Sang-Chul ; Cho, Cheong-Weon ;
Journal of Pharmaceutical Investigation, volume 27, issue 1, 1997, Pages 39~49
Nicotinic acid was mixed with glass powders such as controlled pore glass (CPG), glyceryl controlled pore glass (GPG) and glass beads (GB) at room temperature. The physicochemical properties of nicotinic acid in the various mixtures were examined by differential thermal analysis, X-ray diffraction study. Infrared spectroscopy and BET gas adsorption measurements. The peak area at the melting point from the various mixtures of nicotinic acid and CPG was increased with an increase of nicotinic acid concentration while the broad peak area was remained unchanged in the DTA curve. As shown in the powder X-ray diffraction patterns, the crystalline peaks of nicotinic acid disappeared in mixture with CPG, suggesting the interaction of nicotinic acid and porous powders. It was found that the larger the content of CPG, the higher the ratio of an amorphous state to a crystalline state. BET isotherm showed that as the amount of nicotinic acid was increased, the specific surface area was reduced proportionally to nicotinic acid content of up to 40% and remained constant thereafter. Sublimation of nicotinic acid from the mixture of nicotinic acid and CPG was examined. A large quantity of nicotinic acid was retained in the mixture when stored on various temperatures in vacuo for 10 hours. The nicotinic acid mixtures with CPG or GPG showed a high dissolution rates of nicotinic acid in aqueous solution, especially in the initial dissolution stage. CPG is expected to be a good pharmaceutical excipient to reduce the crystallinity of drugs and to prevent sublimation of drugs.
Pharmacokinetic Interaction of Vancomycin and Probenecid in Rabbits
Lee, Do-Nil ; You, Jae-Sin ; Burm, Jin-Pil ; Choi, Jun-Shik ;
Journal of Pharmaceutical Investigation, volume 27, issue 1, 1997, Pages 51~56
This study was attempted to investigate the pharmacokinetic interaction of vancomycin (10 mg/kg, i.v.) and probenecid (7.5. 15, and 30 mg/kg, oral) in rabbits. The area under curve (AUC) of plasma vancomycin concentration was significantly increased (p<0.01) in rabbits when the probenecid was coadministrated. Volume of distribution (Vd) was significantly decreased (p<0.05) in rabbits coadministrated with probenecid (15 and 30 mg/kg) and total body clearance (CLt) was decreased significantly (p<0.05. p<0.01) in rabbits coadministrated with probenecid (7.5, 15 and 30 mg/kg). There was significant correlation between AUC and probenecid dose. From the results of this experiment, it is desirable to adjust dosage regimen of vancomycin for reduction of side or toxic effect when the probenecid is coadministered in clinical practice.
Effect of Nifedipine on the Ampicillin Absorption
Jeong, Hyun-Jeong ; Yong, Chul-Soon ; Choi, Yoon-Soo ; Oh, Doo-Man ;
Journal of Pharmaceutical Investigation, volume 27, issue 1, 1997, Pages 57~64
antibiotics are absorbed by the dipeptide transporter in the small intestine. These uptakes are coupled to a proton influx. The inward proton gradient is partly induced by the
exchanger and calcium ion is involved in control of this antiport. Interaction between ampicillin which is one of the
antibiotics and nifedipine which is one of calcium channel blocking agents was studied in rats in vivo and with rabbit jejunum mounted on the Sweetana/Grass diffusion cells in vitro. Bioavailability of ampicillin was increased significantly when nifedipine was co-administered orally in rats. There were no differences in the distribution phase and the elimination phase when ampicillin was given either alone or with nifedipine intravenously. Conditions for in vitro experiments were determined. The lift rate of
gas was controlled to 3 bubbles/sec and ampicillin was stable in the Kreb's buffer at pH 6.0. Absorption of ampicillin was the greatest when the completely-stripped serosal membrane was used. Transport of ampicillin from mucosal to serosal side in the rabbit jejunum was enhanced by 32% in the presence of nifedipine (p=0.059). Above results suggest that nifedipine might increase the plasma level of ampicillin via the improved absorption in the intestine rather than the reduction in the elimination or/and alteration in the distribution.
Formulation of Topical Analgesic Preparation for a New Capsaicin Derivative Analgesic, DA-5018 (I) : Establishment of Skin Penetration Evaluation System and Formulation of Topical Cream
Cha, Bong-Jin ; Lee, Eung-Doo ; Kim, Won-Bae ; Lee, Min-Hwa ;
Journal of Pharmaceutical Investigation, volume 27, issue 1, 1997, Pages 65~69
To formulate the topical analgesic preparation of a new capsaicin derivative, DA-5018, a skin penetration evaluation system was established and the effect of composition of formulation on skin penetration using this system was evaluated, The effect of massage on hairless mouse skin penetration and inter-day variation of this effect were investigated using test formulations(cream). In massage group, compared with non-massage group, absolute penetration amount of DA-5018 increased and this experimental system was found to be reproducible, The effects of pH of water phase, ratio of oil/water and the concentration of active ingredient in cream on skin penetration were investigated. The permeation of DA-5018 from the cream increased with increasing pH of water phase to 9. But at pH 10, the permeation of DA-5018 decreased, because of the physical instability of the cream. The permeation of DA-5018 from the cream increased with increasing the ratio of oil/water of the cream. The increase of the content of DA-5018 to 0.3% increased the permeation of DA-5018, but at high concentration(1.0%), the permeation of DA5018 decreased, due to the instability of the cream.
Fabrication and Characterization of Flurbiprofen loaded Chitosan Beads for Periodontal Regeneration
Rhee, Su-Jin ; Park, Yoon-Jeong ; Lee, Seung-Jin ; Chung, Chong-Pyoung ;
Journal of Pharmaceutical Investigation, volume 27, issue 1, 1997, Pages 71~77
With the aim of improving periodontal regeneration efficacy, as a biodegradable local drug delivery device, drug releasing chitosan beads were prepared. Chitosan beads were prepared through the formation of intermolecular or intramolecular ionic interaction bewteen chitosan and sodium tripolyphosphate and were loaded with flurbiprofen. The mean diameter of the beads was
. Drug loading efficiency was improved by regulating the pH of tripolyphosphate solution. The drug release kinetics mainly depended upon the hydrophobic properties of the flurbiprofen, that is, the release of flurbiprofen showed initial burst with rapid release for the first day followed by a levelling off of the release rate. However, the release rate could be controlled by the formulation factor including the pH, concentration of the tripolyphosphate solution, gelation time, drug contents. From these results, flurbiprofen loaded chitosan beads were anticipated as biodegradable local drug delivery devices for periodontal regeneneration.