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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 24, Issue 4 - Dec 1994
Volume 24, Issue 3 - Sep 1994
Volume 24, Issue 3 - Sep 1994
Volume 24, Issue 2 - Jun 1994
Volume 24, Issue 1 - Mar 1994
Selecting the target year
Assay of Nifedipine in the Plasma from Patients with Pulmonary Hypertension
Oh, Doo-Man ; Johnson, Cary E. ; Yong, Chul-Soon ; Choi, Yoon-Soo ;
Journal of Pharmaceutical Investigation, volume 24, issue 3, 1994, Pages 1~9
In order to assay the human plasma concentration of nifedipine in patients with bronchopulmonary dysplasia (BPD) and pulmonary hypertension, a modified high performance liquid chromatography (HPLC) method was applied. The retention times for nifedipine and an internal standard (11-ketoprogesterone) were
min, respectively. Absolute recovery from the plasma was
. Reproducibility was excellent and variability between the runs was small. There was a negligible degradation during the assay procedure. The calibration curve shows a good linearity in the range of the desired plasma concentrations of nifedipine. A stability test of nifedipine in the human plasma shows 8 and 13% degradation during the storage of 5 and 9 months, respectively. There were no interferences on the HPLC assay with any possible medications for the BPD. The method has been used to monitor the drug concentrations in a patient. The concentration-time curve of a patient after a single oral dose of 0.3 mg/kg shows a double-peak phenomenon that was quite different from the previous report, suggesting non-bolus administration. However the hemodynamic responses were corresponding to the plasma concentration levels of nifedipine.
Effects of D-Fructose on the Uptake of Iron by the Intestinal Brush-Border Membrane Vesicles from Rats.
Kim, Ok-Seon ; Lee, Yong-Bok ; Oh, In-Joon ; Koh, Ik-Bae ; Lee, Yeong-Woo ;
Journal of Pharmaceutical Investigation, volume 24, issue 3, 1994, Pages 11~18
We have studied the iron uptake by the purified brush-border membrane vesicles (BBMVs) to determine the effect of fructose on the absorption of iron. BBMVs were prepared by the modified calcium precipitation method, The degree of purification was routinely assessed by the marker enzyme, alkaline phosphatase, and the functional integrity was tested by
uptake. The appearance of membrane vesicles was shown by transmission electron microscopy (TEM). The uptakes of complexes of labeled iron
with fructose and ascorbate were measured with a rapid filtration technique, The uptake rate and pattern of the two iron-complexes, Fe(III)-fructose and Fe(III)-ascorbate, were also observed. A typical overshooting uptake of D-glucose was observed with peak value of
times higher concentration than that at equilibrium. This result was similar to other studies with BBMVs. TEM showed that the size of BBMVs was uniform and we can hardly find any contaminants, Fe(III)-fructose has the higher value of
and the lower value of Km than those of Fe(III)-ascorbate, respectively. It may be concluded that D-fructose is more effective in promoting the iron absorption than ascorbate.
Effect of Water Flux on the Determination of Membrane Permeability Using Single-pass Perfusion
Oh, Doo-Man ;
Journal of Pharmaceutical Investigation, volume 24, issue 3, 1994, Pages 19~25
The single-pass perfusion technique was employed in order to investigate the effect of water flux from the rat jejunum in the normal experimental conditions. Our results suggested that water flux below
of jejunal length was considered normal. Water flux was
of jejunal length in a citrate buffer and should be corrected in order to determine the permeabilities of the compounds. Perfusion rate up to 0.5 ml/min had no effects on the permeability of ampicillin. Neither the effective permeabilities nor the wall permeabilities of aminopenicillins were influenced by water flux during experiments in rats.
Skin Permeation of Flurbiprofen through Excised Rat Skin from Poloxamer 407 Gel
Gil, Hyung-Jun ; Lee, Woo-Young ; Chi, Sang-Cheol ;
Journal of Pharmaceutical Investigation, volume 24, issue 3, 1994, Pages 27~32
In order to reduce systemic side effects following oral administration, flurbiprofen was formulated as transdermal gels consisting of the drug, poloxamer 407 and ethanol in buffer solutions. The effect of formulation variables in the preparation of flurbiprofen gels on skin permeation of the drug was evaluated using Keshary-Chien diffusion cells fitted with excised rat skins. The permeation rate of flurbiprofen through rat skin was directly proportional to initial drug concentration (between 0.1% and 1.0%) in the gel while it was inversely proportional to poloxamer 407 concentration (between 17.5% and 25%). The skin permeation of flurbiprofen was substantially influenced by the gel pH between 3 and 7, exhibiting a maximum at pH 4. The concentration effect of ethanol on the permeation of the drug was negligible in the concentration range of
Factors Affecting the Rate of Release of 5-Fluorouracil from Ethylene-Vinyl Acetate Matrices
Oh, Seaung-Youl ; Chung, Hee-Won ; Cho, Sun-Hang ; Lee, Hai-Bang ;
Journal of Pharmaceutical Investigation, volume 24, issue 3, 1994, Pages 33~39
We have studied the effect of loading amount and particle size on the rate of release of 5-fluorouracil (5-FU) from ethylene-vinyl acetate (EVA) matrix. Release rate increased as the loading amount and particle size increase. We also studied the effect of additives (lactose and algin) on the rate of release of 5-FU. Both algin and lactose promoted the rate of release. The ability to increase the rate is in the order of algin>lactose>5-FU. Scanning electron microscope study clearly shows that large cavities and cracks are created. The results imply that, by the proper combinations of the amount of the additive,
and drug, the rate of drug release can be modulated over a wide range of values.
Effect of Enhancers on the Electrical Properties of Skin: The Effect of Azone and Ethanol
Oh, Seaung-Youl ; Guy, Richard H. ;
Journal of Pharmaceutical Investigation, volume 24, issue 3, 1994, Pages 41~47
The effect of Azone and ethanol on the electrical properties of human and hairless mouse skin was studied and the results were compared. The complex electrical impedance was measured as a function of frequency, and resistance and capacitance were determined from Nyquist plot. After the treatment of human-heat separated epidermis with Azone, contrary to the expectation, resistance increased about 60% and it did not change with time. Capacitance also increased; immediately after the treatment, it was about 110% of pretreatment value and it increased further with time. On the other hand, when hairless mouse skin was treated with Azone, marked changes occured; resistance fell almost to the value of bathing medium itself and capacitance increased to about 200% of its pretreatment value. Similar result were obtained when hairless mouse skin was treated with 100% ethanol. The results suggest that there are differences in the strength of barrier properties of stratum corneum (SC) between human and hairless mouse skin. Overall, the results provide further mechanistic insight into ion conduction through the skin and into the role of SC lipids in skin capacitance.
Studies on Permeation Enhancers for Ocular Peptide Delivery Systems: Pz-peptide as a Novel Enhancer of Ocular Epithelial Paracellular Permeability in the Pigmented Rabbit
Chung, Youn-Bok ; Lee, Vincnet H.L. ;
Journal of Pharmaceutical Investigation, volume 24, issue 3, 1994, Pages 49~57
The objective of this study was to determine whether Pz-peptide, an enhancer of hydrophilic solute permeability in the intestine, could elevate the paracellular permeability of the cornea and conjunctiva in the pigmented rabbit. The in vitro penetration of four hydrophilic solutes, mannitol (MW 182), fluorescein (MW 376), FD-4 (FITC-dextran, 4 KDa), and FD-10 (FITC-dextran, 10 KDa) across the pigmented rabbit cornea and conjunctiva was studied either in the presence or absence of 3 mM enhancers. Drug penetration was evaluated using the modified Ussing chamber. The conjunctiva was more permeable than the cornea to all four markers. EDTA and cytochalasin B showed higher effects on marker transport than Pz-peptide, but Pz-peptide elevated the corneal transport of mannitol, fluoresein, and FD-4 by 50%, 26%, and 50%, respectively, without affecting FD-10 transport. Possibly due to the leakier nature of the conjunctiva, 3 mM Pz-peptide elevated the transport of only FD-4 by about 45%, without affecting the transport of other markers. Furthermore, the transport of Pz-peptide itself across the cornea and conjunctiva increased with increasing concentration in the 1-5 mM range, suggesting that Pz-peptide enhanced its own permeability, possibly by elevating paracellular permeability. Effects of ion transport inhibitors on Pz-peptide transport were then investigated. PZ-peptide penetration was not changed by mucosal addition of
hexamethylene amiloride, inhibiting serosal
ouabain, or replacing
with choline chloride in the mucosal side buffer. These results seggested that Pz-peptide enhanced the paracellular permeability of rabbit cornea and conjunctiva and further indicate that ion transporters were not involved in the Pz-peptide induced elevation of paracellular marker permeability.
Studies on Drug Absorption Characteristics for Development of Ocular Dosage Forms: Ocular and Systemic Absorption of Topically Applied
in the Pigmented Rabbit
Lee, Yong-Hee ;
Journal of Pharmaceutical Investigation, volume 24, issue 3, 1994, Pages 59~66
The objective of this study was to determine the influence of drug lipophilicity on the extent of ocular and systemic absorption following topical solution instillation in the pigmented rabbit.
of various lipophilicity were chosen as model drugs,
of a 15 mM drug solution in isotonic pH 7.4 buffer was instilled, and ocular tissue and plasma drug concentrations were monitored. Ocular absorption was apparently increased in all eye tissues, but non-corneal absorption ratio was decreased by increasing of drug lipophilicity. Systemic bioavailability was ranged from 61% for atenolol to 100% for timolol, and at least 50% of the systemically absorbed drug reached the blood stream from the nasal mucosa. Occluding the nasolacrimal duct for 5 min reduced the extent of systemic absorption of timolol and levobunolol, but did not do so for atenolol and betaxolol. Taken together, the ocular absorption of topically applied ophthalmic drugs would be modest for lipophilic drugs. By contrast, the systemic bioavailability would be modest for drugs at the extremes of lipophilicity, and the nasal contribution to systemically absorbed drug diminished with increasing of drug lipophilicity.
Application of Experimental Design to Optimize Vitamin C-90 Tabletting Performance
Chang, Kuei-Tu ;
Journal of Pharmaceutical Investigation, volume 24, issue 3, 1994, Pages 67~77
The RMS statistical approach has demonstrated its potential in developing pharmaceutical dosage forms and in improving tabletting performance. Using an optimized formula, the tabletting performances of vitamin C-90 such as compressibility, disintegration time, lubrication and friability are significantly enhanced when compared with the performance of a traditional test formula. More important, this method also enables us to serve our customers better. Any customized modification of a suggested formula or any technical problem related performance etc. can be readily resolved by simple examination of the models.
Stabilization of Doxorubicin Hydrochloride in Injections
Lee, Sang-Cheol ; Nam, Sang-Cheol ; Kim, Chun-Seong ; Shin, Hyun-Jong ; Paik, Woo-Hyun ;
Journal of Pharmaceutical Investigation, volume 24, issue 3, 1994, Pages 109~113
Effects of various formulation factors using
orthogonal arrays with the stability of doxorubicin hydrochloride injections(DHls) were investigated. The degradation of DHI may be occured by pH, temperature, light and metal ions. It is known that DHI should be stored on refrigerated condition of
because of its unstability on the room temperature. The employed factors were sodium chloride as isotonic solution, sodium bisulfite or sodium pyrosulfite as an antioxidant, disodium edetate as a chelating agent, methyl parahydroxybenzoate as a dissolution time shortening agent, and hydrochloric acid or citric acid as a pH adjusting agent at
. From the results of
orthogonal arrays, an optimal formula, including sodium chloride, disodium edetate, sodium bisulfite and hydrochloric acid, was obtained and the shelf-life of the formula was determined as 560 days approximately.
Damage of Ibuprofen Suppository on Rectal Mucosa of Rats
Lee, Sung-Hack ; Kim, Moon-Kyoung ; Han, Yong-Hae ; Shim, Chang-Koo ;
Journal of Pharmaceutical Investigation, volume 24, issue 3, 1994, Pages 115~129
In the present study, quantitative and qualitative histology was used to assess the effects of ibuprofen suppositories with various treatments on the rectal mucosa of rats. Two suppositories were prepared with Witepsol W35 and compared with two commercial ibuprofen suppositories Reference I (Showa Pharm.ind., Tokyo, Japan), Reference II (P.Pharm., Seoul, Korea). Single and multiple dose(dosing interval 4 hr, n=4) studies were conducted. All suppositories significantly increased epithelial cell loss, but the extent of rectal irritation was variable. These studies showed that the incorporation of ibuprofen into the suppository bases increases the morphological change in rectal tissue both for the single and multiple administrations of suppositories, but which was significantly recovered within 24 hr although the interanimal variability in scores was very substantial. Multiple administration of ibuprofen suppositories caused significant damage to rectal mucosa, but it must be considered that these were under the severe condition, that is, interval of administration (4 hr) was three times shorter than normal interval of administration and dose was fifteen times larger than usual human dose. Aluminum oxide
, a dispersing agent, slightly increased the irritation of rectal mucosa in rats at 5 hr and 24 hr after multiple administration, but it was possible to ignore the difference of irritation in the data at 5hr and 24hr after single administration. Finally, it was concluded that Witepsol W35 and ibuprofen had a slight rectal mucosa-irritating effect on the usual human dose, and ibuprofen suppositories prepared with Witepsol W35 or Witepsol W35,
showed almost similar extent of rectal irritation with commercial ibuprofen products.
Delivery System of Daunorubicin by Red Blood Cells
Ham, Seong-Ho ; Song, Kyung ; Ko, Gun-Il ; Kim, Jae-Baek ; Sohn, Dong-Hwan ;
Journal of Pharmaceutical Investigation, volume 24, issue 3, 1994, Pages 131~137
Drug delivery system by the use of red blood cells was established to sustain the release of drugs in the circulatory system by the intravenous injection. The entrapment method by the preswelling technique was re-examined and evaluated for searching the new entrapping conditions without hemolysis. The addition of 4 volume of
balanced salt solution (HBSS) into 1 volume of 50% red blood cells suspension did not induce the hemolysis and change the hematocrit level in this experimental condition (within 15 min). Most of daunorubicin could be entrapped into red blood cells within 15 min. While the intracellular adenosine triphosphate (ATP) level followed by the entrapment was reduced to 86% of normal ATP level, the membrane fluidity and the shape factor of red blood cells were not altered. The release rate of daunorubicin from red blood cells was affected by the hemolysis under this condition. To maintain the intracellular ATP in red blood cells, the new reaction buffer was made With the addition of ATP and sodium pyruvate during the entrapment procedure because the hemolysis during the release test would reflect the loss of intracellular ATP that might result in the decrease of the viability in vivo. The addition of ATP raised the intracellular ATP level, which protect the hemolysis during the release test.
Studies on the Dissolution of the Famotidine Matrix Tablets using Polymer
Choi, G. H. ; Han, S.S. ; Sohn, D.H. ; Kim, J.B. ;
Journal of Pharmaceutical Investigation, volume 24, issue 3, 1994, Pages 139~144
The effect of some formulation variables on the release rate of famotidine, a
receptor antagonist, from cellulose matrices containing hydroxypropylcellulose (HPC) in different ratios and types was investigated. The effects of tablet shape and compression pressure on dissolution rate of famotidine were studied. And the effect of the pH of dissolution media was also studied. Increase in the ratio of polymer to drug decreased the release rate of famotidine. Increase of the polymer viscosity also decreased the release rate. The release rate of famotidine was dependent on the pH of dissolution media. The release rate of drug was not much dependent on the compression pressure but dependent on the tablet shape and/or surface area. Consequently, the release rate of famotidine can be modified by changing the HPC contents, types of polymers with different viscosity grades or using appropriate fillers.
Effects of Suppository Bases and Additives on Rectal Absorption of Ibuprofen Lysinate
Jeon, Hong-Ryeol ; Park, Dong-Woo ; Lee, Seung-Mok ; Yi, Jung-Woo ; Choi, Young-Wook ;
Journal of Pharmaceutical Investigation, volume 24, issue 3, 1994, Pages 145~153
Ibuprofen is an effective non-steroidal anti-inflammatory drug (NSAID), but it has several limitations in clinical application because of low solubility in water and gastrointestinal irritation. A water-soluble salt of ibuprofen, ibuprofen Iysinate, has been synthesized to overcome these shortcomings, and it was formulated as suppository for rectal administration. Witepsol and polyethylene glycols were employed as suppository bases for either ibuprofen or ibuprofen Iysinate, in order to compare the bioavailability in rabbits. The plasma concentrations of ibuprofen were assayed by HPLC after a rectal administration of ibuprofen and ibuprofen Iysinate, respectively. In addition to the comparison of two suppository bases, the other factors which affect on rectal absorption were also evaluated, especially in the point of not only particle size and shape of ibuprofen Iysinate but also effects of additives such as stearic acid, cetyl alcohol and capric acid. And pharmacokinetic parameters such as AUC,
were also compared. In conclusion, spray-dried ibuprofen Iysinate which was polyporous and spherical shape gave an increased absorption from the rectal formulations with Witepsol Hl5 and stearic acid.
Mucoadhesion, Swelling and Drug Release Characteristics of Hydroxypropylcellulose/Carbopol Solid Dispersions
Kim, Sang-Heon ; Yang, Su-Geun ; Shin, Dong-Sun ; Lee, Min-Suk ; Choi, Young-Wook ;
Journal of Pharmaceutical Investigation, volume 24, issue 3, 1994, Pages 155~165
Some mucoadhesive polymers such as hydroxypropylcelluose (HPC) and carbopol-934 (CP) have been employed for the preparation of mucoadhesive polymeric systems, and their physical properties including mucoadhesion, swelling, and drug release were evaluated. A new simple experimental technique that can quantitatively measure the bioadhesive properties of various polymeric systems has been developed by the methods of detachment force test. As the polymeric systems, the discs of freeze-dried HPC/CP solid dispersions were prepared. The mucosa used in these tests were upper, middle, and lower parts of small intestine of male rats weighing
. Detachment forces were increased as the mole fraction of CP increased in discs of HPC/CP solid dispersions. In the points of intestinal site dependence of mucoadhesion, the solid dispersions revealed non-specific mucoadhesion to the intestine. Swelling and drug release characteristics of mucoadhesive polymeric systems were studied extensively to find out the feasibility for the oral controlled delivery systems. Swelling ratio, expressed as the final height/initial height, has been determined in various pH buffer solutions. Hydrochlorothiazide (HCT) was employed as a model drug for release study. Apparent swelling and drug release rate constants,
respectively, were obtained from the square-root time plot of either swelling ratio or released amount of drug, particularly for the time periods before reaching the equilibrium. As a result, the swelling ratio of HPC/CP solid dispersions was increased as the weight percentage of CP increased. Similarly, the release of HCT from the solid dispersions was dependent on pH changes and CP contents, resulted in the slower release of HCT with the increases of pH and CP contents.
Preparation and Evaluation of the Controlled-release Dosage Form of Amoxicillin
Jee, Ung-Kil ; Jeon, Un-Jong ; Lee, Gye-Won ; Han, Kun ; Chung, Youn-Bok ;
Journal of Pharmaceutical Investigation, volume 24, issue 3, 1994, Pages 167~176
The microcapsules of amoxicillin using stearyl alcohol and polyethyleneglycol 8000 (PEG 8000) were prepared by a emulsion melted-cooled process in water phase. The size distribution, dissolution test, observation with SEM and in vivo test were investigated. The microcapsules obtained were spherical, uniform and free flowing particles. The release of drug from microcapsule was increased in proportional to the content of PEG 8000. As the PEG 8000 content increased, the particle size of microcapsule was decreased. Sanning electron micrograph study revealed that microcapsules had comparatively rough surfaces as drug content was increased. The
after administration of amoxicillin microcapsules was more increased 40% as compared with the AUC after administration of amoxicillin powder in rabbits.
Evaluation of Bioavailability of Bioadhesive Microcapsules Containing Cephalexin
Han, Kun ; Kim, Jung-Hwan ; Chung, Youn-Bok ; Jee, Ung-Kil ;
Journal of Pharmaceutical Investigation, volume 24, issue 3, 1994, Pages 177~186
Bioadhesive microcapsules of cephalexin, using Eudragit RS/RL coated with polycarbophil or carbopol, were evaluated biopharmaceutically. The GI transit of microcapsules in rats was studied. Bioadhesive microcapsules coated with polycarbophil or carbopol were shown to have substantially longer GI transit time than Eudragit RS/RL microcapsule. The delay in transit time was due to bioadhesion of the polymer to the mucin-epithelial cell surface which was clearly observable on animal autopsy. Plasma drug levels in rabbits showed that bioadhesive microcapsules resulted in a longer duration of action and greater bioavailability than other microcapsule or drug powder. Thus, the principle of bioadhesion can significantly improve therapy, due to a reduced rate of gastric emptying, an increase in contact time, and the intimacy of contact of the drug with the absorbing membrane.