Go to the main menu
Skip to content
Go to bottom
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
Editor in Chief :
Volume & Issues
Volume 31, Issue 4 - Dec 2001
Volume 31, Issue 3 - Sep 2001
Volume 31, Issue 2 - Jun 2001
Volume 31, Issue 1 - Mar 2001
Selecting the target year
Synthesis and Biopharmaceutical Properties of Ceftezole Butyrolactone Ester, a Novel Prodrug of Ceftezole
Lee, Jin-Hwan ; Park, Jae-Young ; Choi, Jun-Shik ; Ko, Jae-Won ;
Journal of Pharmaceutical Investigation, volume 31, issue 3, 2001, Pages 143~150
Butyrolactone ester of ceftezole (CFZ-BL) was synthesized by esterification of ceftezole (CFZ) with
. The synthesis was confirmed by spectroscopic analysis. CFZ-BL was more lipophilic than CFZ when the lipophilicity was assessed by partition coefficients between n-octanol and water at various pH. CFZ-BL itself did not show any microbiological activity in vitro, but serums taken after oral administration of CFZ-BL showed substaintial microbiological activity indicating that CFZ-BL is converted to microbiologically active metabolite, probably CFZ, in the body. The conversion was confirmed by in vitro incubation study, in which CFZ-BL was incubated in some body tissues of rabbit. Liver homogenate showed fastest conversion of CFZ-BL among the tissues tested (blood and intestine). Thus, CFZ-BL appeares to be rapidly metabolized in the liver to CFZ following oral administration. The metabolism process appears to be hydrolysis of the ester to CFZ, the parent drug of CFZ-BL. In vivo metabolism of CFZ-BL to CFZ was confirmed by analying CFZ by HPLC. CFZ concentration in the serum samples taken after oral administration of CFZ-BL were higher than those in the serum samples taken after oral administration of equivalent amount of CFZ. Oral bioavailability of CFZ-BL, a prodrug of CFZ, was 1.45-fold higher than that of CFZ in rabbits possibly due to enhanced lipophility and absorption of the prodrug.
Complexation of Progesterone with Cyclodextrins and Design of Aqueous Parenteral Formulations
Choi, Hee-Jeong ; Chun, In-Koo ;
Journal of Pharmaceutical Investigation, volume 31, issue 3, 2001, Pages 151~160
The purpose of this study is to investigate the interaction of progesterone with various cyclodextrins (CDs) in the aqueous solution and in solid state, and finally to formulate a parenteral aqueous formulation. CDs used were
(TMCD). The solubility studies of progesterone were performed in the presence of various CDs as a function of concentration or temperature. The solubility of progesterone increased in the rank order of
< HPCD < DMCD < SBCD. Addition of SBCD (200 mg/ml) in water increased the aqueous solubility
about 3,200 times, and lowering the temperature facilitated the solubilization of progesterone. However, the addition of HPCD and SBCD in 20:80 (v/v) polyethylene glycol 300-water and propylene glycol-water cosolvents markedly decreased the solubility of progesterone, compared with solubilizing effects in water. Physical mixtures and solid dispersions of progesterone with HPCD or SBCD were prepared, and evaluated by differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR), near IR spectroscopy and dissolution studies. By DSC and IR studies, it was found that progesterone was dispersed in HPCD in monotectic state and dissolved rapidly from both solid dispersions. Based on solubility studies, new aqueous progesterone fonnulations (5 mg/ml) containing SBCD (200 mg/ml) could be prepared and did not form precipitates even after 2 months at
. The solution was transparent when mixed with normal saline and 5% dextrose injection at 1: 1, 1:10 and 1:20 (v/v) even after 7 days. Permeation rates of progesterone through a cellulose membrane from 20% PEG 300 solution
containing HPCD or SBCD were compared with oily formulation. Permeation of progesterone from oily formulation did not occur up to 8 hr, but aqueous formulations showed fast permeation rates from early stage of permeation study. The addition of HPCD or SBCD retarded the permeation rates of progesterone with the increase of CD concentrations, suggesting the possibility of a controlled absorption from the site administered intramuscularly. These results demonstrate that it is feasible to develop a new progesterone parenteral aqueous injection (5 mg/ml) using SBCD.
Pharmacokinetics of Acebutolol and Diacetolol After Oral Administration of Acebutolol in Rabbits with Folate-Induced Renal Failure
Choi, Jun-Shik ; Lee, Jin-Hwan ;
Journal of Pharmaceutical Investigation, volume 31, issue 3, 2001, Pages 161~165
Acebutolol (ABT) is almost absorbed after oral administration, but its bioavailability is reduced because of considerable first-pass metabolism in the gastrointestine and liver. The purpose of this study was to report the pharmacokinetic changes of ABT and its metabolite, diacetolol (DAT) after oral administration of acebutolol to control rabbits and rabbits with mild and severe folate-induced renal failure (FIRRs). Both of the area under the plasma concentration-time curve
of ABT and DAT were significantly increased in mild (p<0.05) and severe FIRRs (p<0.01), but the
of DAT was more influenced than that of ABT in severe rabbits. There was a good correlation between serum creatinine and both of
of ABT and DAT. The elimination half-life of ABT and DAT was significantly prolonged in mild (p<0.05) and severe (p<0.01) FIRRs, but the half-life of DAT was more influenced than that of ABT in severe FIRRs. The results suggest that the dosage of acebutolol should be adjusted according to the degree of renal disorder on the base of the serum creatinine concentration.
Solid Lipid Nanoparticle Formulation of All Trans Retinoic Acid
Lim, Soo-Jeong ; Lee, Mi-Kyung ; Kim, Chong-Kook ;
Journal of Pharmaceutical Investigation, volume 31, issue 3, 2001, Pages 167~172
All-trans retinoic acid (ATRA), vitamin A acid, has been shown to exert anticancer activity in a number of types of cancers, particularly in acute promyelocytic leukaemia (APL). Due to its highly variable bioavailability and induction of its own metabolism after oral treatment, development of parenteral dosage forms are required. However, its poor aqueous solubility and chemical unstability give major drawbacks in parenteral administration. This study was undertaken to investigate a possibility to develop a parenteral formulation of ATRA by employing solid lipid nanoparticle (SLN) as a carrier. By optimizing the production parameters and the composition of SLNs, SLNs with desired mean particle size (<100 nm) as a parenteral dosage form could be produced from trimyristin (as solid lipid), Egg phosphatidylcholine and Tween 80 (as SLN stabilizer). The mean particle size of SLN formulation of ATRA was not changed during storage, suggesting its physical stability. Thermal analysis confirmed that the inner lipid core of SLNs exist at solid state. The mean particle size of ATRA-loaded SLNs was not significantly changed by the lyophilization process. ATRA could be efficiently loaded in SLNs, while maintaining its anticancer activity against HL-60, a well-known APL cell line. Furthermore, by lyophilization, ATRA loaded in SLN could be retained chemically stable during storage. Taken together, our present study demonstrates that physically and chemically stable ATRA formulation adequate for parenteral administration could be obtained by employing SLN technology.
Synthesis of [P(AA-co-PEGMM)] Copolymer Films and its Physicochemical Characteristics
Kim, Joun-Sik ; Park, Jeong-Sook ; Han, Kun ;
Journal of Pharmaceutical Investigation, volume 31, issue 3, 2001, Pages 173~180
The physicochemical characteristics such as glass transition temperature (Tg), surface energy, swelling and FT-IR of [P(AA-co-PEGMM)], a copolymer of acrylic acid (AA) and polyethyleneglycol monoethylether mono methacrylate (PEGMM), were evaluated. The Tg of [P(AA-co-PEGMM)] decreased with increasing PEGMM content. [P(AA-co-PEGMM)] with 18 mole% PEGMM had the Tg of about
, the similar physiological temperature of human. Moreover, [P(AA-co-PEGMM)] with lower PEGMM content had higher hydration and expected lower mucoadhesive strengths. To predict the mucoadhesiveness of [P(AA-co-PEGMM)] films, the contact angle of films were measured. With the increasing content of PEGMM of films, the contact angle was increased and the higher mucoadhesive forces was expected. ATR-FTIR studies revealed that the addition of the PEG moiety in AA increased the potential of hydrogen bonding for [P(AA-co-PEGMM)] as compared to cross linking polyacrylic acid (cr-PAA) because the oxygen in the repeat unit of PEG contributed in the formation of hydrogen bonding in the presence of mucin solution.
Development of Transdermal Drug Delivery System for the Combination of Physostigmine and Procyclidine
Park, Soon-Cheol ; Choi, Hoo-Kyun ;
Journal of Pharmaceutical Investigation, volume 31, issue 3, 2001, Pages 181~184
The purpose of this study was to develop transdermal drug delivery system (TDDS) for the combination of physostigmine and procyclidine. The effects of various pressure sensitive adhesives (PSA) on the percutaneous absorption of procyclidine across hairless mouse skin were evaluated to select an appropriate PSA. In addition, the influences of various vehicles on the percutaneous absorption of procyclidine from PSA matrix across hairless mouse skin were evaluated using flow-through diffusion cell system at
. Physostigmine did not have any influence on the permeation rate of procyclidine. The flux of procyclidine was the highest in silicone and PIB and was relatively lower in SIS, Acryl, and SBS adhesive matrices, however, their use was limited by the crystallization of the drug in the matrix. Among acrylic adhesives, the permeability of procyclidine was the highest from poly (ethylene oxide) grafted acrylic adhesive. Some enhancers show different enhancing effect depending on the drug, however, many of the tested enhancers showed enhancing effect for the permeation of both procyclidine and physostigmine to some extent.
EP 40 showed the highest enhancing effect on the permeation of both compounds. The size of TDDS to provide required permeation rate was estimated to be
based on available information.
Virus-like Particles Containing Cytokine Plasmid DNA
Oh, Yu-Kyoung ; Son, Tae-Jong ; Sin, Kwang-Sook ; Kang, Min-Jeong ; Kim, Jung-Mogg ; Kim, Nam-Keun ; Ko, Jung-Jae ; Kim, Chong-Kook ;
Journal of Pharmaceutical Investigation, volume 31, issue 3, 2001, Pages 185~190
Human papillomavirus (HPV) infection is known to cause cervical cancers. Human papillomavirus-like particles (VLP) have been studied as preventive vaccines of cervical cancers. To develop VLP as a therapeutic gene carrier, we studied the method to encapsulate cytokine genes in virus-like particles. HPV type 16 capsid L1 genes were amplified by polymerase chain reaction and cloned into T vector. L1 gene was then inserted into baculovirus transfer vector. The clone of baculovirus encoding L1 gene was isolated and used to express L1 protein in Sf 21 insect cells. VLP were purified by CsCl density gradient and ultracentrifugation. VLP were disassembled to capsomer units by treatment of a reducing agent. Given that interleukin-2 (IL-2) genes have been used in anticancer gene therapy and as a molecular adjuvant, IL-2 cytokine plasmids were chosen as a model gene. IL-2 plasmids were incubated with the disassembled capsomer suspension. To reassemble the particles, the mixture of capsomers and cytokine plasmids was dialyzed. The disassembly and reassembly of VLP were confirmed by transmission electron microscopy. The entrapment of cytokine plasmids in reassembled VLP was tested by the stability of plasmids against DNase I. After treatment of reassembled virus-like particles with DNase I, discrete IL-2 DNA band was observed. Our results indicate that IL-2 cytokine plasmid (3.5 kb size) can be encapsulated in the virus-like particles, suggesting the potential of VLP as a gene delivery system. Moreover, VLP containing the adjuvant cytokine plasmids might function as more effective subunit vaccines.
Antigenicity of Protein Entrapped in Poly(lactide-co-glycolide) Microspheres
Song, Seh-Hyon ; Cho, Seong-Wan ; Shin, Taek-Hwan ; Yoon, Mi-Kyoung ; Choi, Young-Wook ;
Journal of Pharmaceutical Investigation, volume 31, issue 3, 2001, Pages 191~196
Biodegradable polymeric microspheres were studied for their usefulness as carriers for the delivery of vaccine antigens. However, protein antigen could be denatured during microencapsulation processes due to the exposure to the organic phase and stress condition of cavitation and shear force. Therefore this study was carried out to re-evaluate the degree of protein denaturation during microencapsulation with poly(lactide-co-glycolide) (PLGA) copolymer. PLGA microspheres containing ovalbumin (OVA), prepared by W/O/W multiple emulsification method, were suspended in pH 7.4 PBS and incubated with shaking at
. Drug released medium was collected periodically and analyzed for protein contents by micro-BCA protein assay. In order to evaluate the protein integrity, release medium was subjected to the analyses of SDS-PAGE and size exclusion chromatography (SEC). And enzyme-linked immunosorbent assay (ELISA) was introduced to measure the immunoreactivity of entrapped OVA and to get an insight into the three-dimensional structure of epitope. The structures of entrapped protein were not affected significantly by the results of SDS-PAGE and SEC. However, immunoreactivity of released antigen was varied, revealing the possibility of protein denaturation in some microspheres when it was evaluate by ELISA method. Therefore, in order to express the degree of protein denaturation, antigenicity ratio (AR) was obtained as follows: amount of immunoreactivity of OVA/total amount of OVA released
. ELISA method was an efficient tool to detect a protein denaturation during microencapsulation and the comparison of AR values resulted in more accurate evaluation for immunoreactivity of entrapped protein.
Assay Method for Lectin-conjugated Ellagitannin Encapsulated in Liposomal Formulations
Jeon, Hyun-Joo ; Choi, Young-Wook ;
Journal of Pharmaceutical Investigation, volume 31, issue 3, 2001, Pages 197~200
Lectin-conjugated ellagitannin (LET), a newly introduced melanoma-specific antitumor agent which has been synthesized by conjugation of wheat germ agglutinin as a lectin with praecoxin A as an ellagitannin, was encapsulated into sterically stabilized liposomes (SSL). Modified Folin phenol method was established for the quantitation of LET contents in liposomal formulations protein employing the standard calibration curve with bovine serum albumin. After removal of phospholipid by organic solvent extraction, which interferes the specific selectivity of the Folin-Ciocalteu reagent with the protein, recovery of LET was
and the encapsulation efficiency was revealed as
for 2.5 mg/ml LET solution.