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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 27, Issue 4 - Dec 1997
Volume 27, Issue 3 - Sep 1997
Volume 27, Issue 2 - Jun 1997
Volume 27, Issue 1 - Mar 1997
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Enzymatic Degradation and Stabilization of Thyrotropin Releasing Hormone in Various Rabbit Mucosa Extracts
Chun, In-Koo ; Shin, Dong-Won ;
Journal of Pharmaceutical Investigation, volume 27, issue 2, 1997, Pages 99~108
To evaluate the feasibility of mucosal delivery of thyrotropin releasing hormone (TRH) through various mucosae, enzymatic degradation and stabilization of TRH in the nasal, rectal and duodenal extracts of rabbits were studied. TRH in the extracts was assayed by HPLC and its degradation was found to follow apparent first-order kinetics. The residual concentrations of TRH in the mucosal extracts of nasal, rectal and duodenal segments after 24 hr of incubation were found to be
and 0%, and in the serosal extracts,
, respectively. This result suggests that there is a significant difference in the activity of TRH-degrading enzymes among the sites of administration. The inhibition of TRH degradation in the mucosa extracts was kinetically investigated using various additives such as thimerosal, benzalkonium chloride, disodium edetate,
, dithiothreitol and dithioerythritol, and
values of inhibitors were calculated. The results obtained showed that thimerosal (0.5 mM) and benzalkonium chloride (0.141 mM) protected TRH from the enzymatic degradation in all the mucosa extracts more than 95% after 24 hr of incubation.
Effect of Phenobarbital on the Nonlinear Pharmacokinetics of Naproxen
Lee, Yong-Bok ; Chae, Myung-Ae ; Koh, Ik-Bae ;
Journal of Pharmaceutical Investigation, volume 27, issue 2, 1997, Pages 109~117
In order to elucidate the effect of phenobarbital (PB) on the nonlinear pharmacokinetic behavior of naproxen (NAP), we compared the dose dependent hepatic intrinsic clearance, biliary excretion and protein binding of NAP in control rats to those in the PB-pretreated rats which were intraperitoneally pretreated with PB sodium (75 mg/kg) once a day for four days. NAP was injected via femoral (1.5 mg/kg) and portal(0.25, 0.5, 1.5, 15 and 30 mg/kg) vein to the control and PB-pretreated rats, respectively. And also, we measured the plasma free fraction of NAP with the equilibrium dialysis method and the biliary excreted total amounts of NAP in both rats. Plasma free fraction of NAP was decreased in lower concentration than
of NAP due to PB pretreatment. In higher concentration, however, plasma free fraction was increased. These in vitro results suggest that the total protein concentration was increased but the total binding capacity of NAP to protein was decreased by PB-pretreatment. The total plasma clearance and the hepatic intrinsic clearance of NAP had similar values in both groups, respectively. And, both clearances of NAP were significantly increased by PB-pretreatment. Even though the plasma free fractions of NAP in both groups were constantly remained within the concentration range according to the increase of administration dose, the hepatic intrinsic clearances of NAP were significantly increased in both groups with the increased dose. And, the biliary excreted total amounts of NAP were significantly increased by PB-pretreatment at the lower dose, but decreased at the higher dose. These in vivo results suggest that NAP represents the uncommon nonlinear pharmacokinetic behavior that the hepatic intrinsic clearance was enhanced with the increased dose, and that PB enhances further the hepatic intrinsic clearance of NAP with the increased dose due to its enzyme induction effect.
Structural and Physicochemical Studies on DA-5018, a New Capsaicin Derivative
Kim, Heung-Jae ; Lee, Jong-Jin ; Lee, Eung-Doo ; Shim, Hyun-Joo ; Lee, Sang-Deuk ; Ok, Kwang-Dae ; Kim, Won-Bae ; Park, No-Sang ;
Journal of Pharmaceutical Investigation, volume 27, issue 2, 1997, Pages 119~123
The physicochemical and structural properties of new capsaicin derivative, DA-5018, were examined. The reference standard of this compound was obtained by the recrystallization. A method for the determination of the dissociation constant of the compound is described. pH-solubility and distribution coefficient were determined by chromatographic method. Fundamental properties on thermal behaviors were investigated by TG, DTA and DSC. Structural analysis based on spectroscopic method coincided with the chemical structure of DA-5018. Approximate dissociation constant of the compound determined by UV spectral method was 9.35. Solubilities and partition coefficients in various pH buffer solution appeared pH-dependency. No crystal transition or further transition was found in the thermal analysis. This compound showed good stability, but pH 13 buffer and acetone made some degradative products.
Synthesis and Biopharmaceutical Studies of Ceftezole Ethoxycarbonyloxyethyl Ester
Park, Yong-Chai ; Lee, Jin-Hwan ; Park, Jae-Young ;
Journal of Pharmaceutical Investigation, volume 27, issue 2, 1997, Pages 125~131
Ethoxycarbonyloxyethyl ester of ceftezole (CFZ-ET) was synthesized as a prodrug by esterification of ceftezole (CFZ) with ethoxycarbonyloxyethyl chloride and was confirmed by spectroscopic analyses. CFZ-ET was more lipophillic than CFZ as assessed by n-octanol and water partition coefficients at various pH. CFZ-ET itself did not show any microbiological activity in vitro, but showed substaintial microbiological activity after oral administration of CFZ-ET, indicating that CFZ-ET is converted to microbiologically active metabolite, probably CFZ, in the body. When CFZ-ET was incubated in blood, liver and intestine homogenates of rabbits, liver homogenate showed the fastest conversion of CFZ-ET. CFZ-ET appears rapidly metabolized in the liver when given orally due to the hydrolysis of the ester to CFZ, the parent drug of CFZ-ET. In vivo metabolism of CFZ-ET to CFZ was confirmed in rabbit by HPLC analysis. CFZ-ET were higher than those in the serum samples taken after oral administration of equivalent amount of CFZ. Oral bioavailability of CFZ-ET was 1.5-fold higher than that of CFZ in rabbits because of enhanced lipophilicity and absorption. Based on these findings, CFZ-ET appears useful as a prodrug of CFZ to improve the oral bioavailability of CFZ.
Oral Mucosal Adhesive Tablets of Omeprazole
Jung, Jae-Hee ; Choi, Han-Gon ; Park, Sun-Joo ; Ryu, Jei-Man ; Yoon, Sung-June ;
Journal of Pharmaceutical Investigation, volume 27, issue 2, 1997, Pages 133~137
Buccal absorption test of omeprazole in human was performed to determine the permeability of the drug molecule through oral mucous membrane. Oral mucosal adhesive tablets of omeprazole were prepared by compressing the omeprazole with a mixture of sodium alginate and hydroxypropylmethyl cellulose (HPMC) as bioadhesive polymers, magnesium oxide (MgO) as a stabilizer and sodium carboxymethyl cellulose (Na CMC) or cros-carmellose sodium (Ac-Di-Sol) as disintegrants. The bioadhesive force, stability in saliva and release characteristics of the tablets were evaluated. Omeprazole was absorbed about 23% in 15 min through human buccal mucous membrane. Furthermore, omeprazole was stable in saliva for more than 8 hrs when MgO was added to the tablet as the amount of 2.5 fold of omeprazole. The release rate of omeprazole was increased with increasing the amount of sodium alginate in the tablet. From these results, it is suggested that tablets composed of [omeprazole/HPMC/sodium alginate/MgO/Ac-Di-Sol and/or Na CMC (20/6/24/50/10) (mg/tablet)] are potential candidate for buccal drug delivery system.
Stabilization of Epidermal Growth Factor in Aqueous Solution and Ointment Base
Kim, Chong-Kook ; Kim, Kyoung-Mi ; Kwon, Soo-Yeon ;
Journal of Pharmaceutical Investigation, volume 27, issue 2, 1997, Pages 139~143
Epidermal growth factor (EGF) is a mitogen which activate the proliferation of basal cells in skin, which implicate the wound healing in severe skin damage such as burn. To carry out the preclinical test for the pharmacological action of EGF, EGF in transdermal delivery system must be stable. Since EGF is a protein susceptible to proteolysis and unstable in aqueous solution, in vitro stabilization of EGF is prerequisite for the formulation. In this study, effect of additives on the stability of EGF is investigated in vitro. The stability of EGF in aqueous solution was enhanced with the various water-soluble polysaccharides such as HPMC, sorbitol, mannitol and dextrin. EGF was successfully extracted from the ointment with 5% HPMC solution, and EGF in aqueous solution and ointment was also successfully stabilized with 5% HPMC. The ointments prepared with different amount of EGF were applied on the damaged dorsal skin of rats for the determination of optimal concentration of EGF. The ointment with EGF
showed good wound healing action on the damaged skin of rats.
Effect of Several Solvent Extracts from Paeoniae Radix on Experimental Hyperlipidemia in Rats
Ro, Hwan-Seong ; Ko, Woo-Kyoung ; Yang, Hyun-Ok ; Park, Kun-Koo ; Cho, Young-Hwan ; Park, Hyoung-Sup ;
Journal of Pharmaceutical Investigation, volume 27, issue 2, 1997, Pages 145~151
Hexane, chloroform, methanol and water extracts of Paeoniae Radix were tested on the experimentally induced hypercholesterolemia in rats for lowering effect of serum lipoprotein contents. Hyperlipidemia was induced on male Wistar rats by feeding high cholestetrol diet for 7 days. Serum lipid profile was verified on these rats by measuring total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL), and low density lipoprotein cholesterol (LDL). Then, the diet was changed to normal. At the same time, hexane, chloroform, methanol and water extract of Paeoniae Radix were given orally on daily basis, and the changes in the serum lipid profile were assessed for 4 weeks. Methanol extract of Paeoniae radix decreased TC level at 1, 2, and 4 week point significantly, and water extract decreased TC level at 4 week point significantly comparing with the control group.