• YAKHAK HOEJI
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• v.47 no.2
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• pp.78-84
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• 2003

Local anesthetics are used to reduce pain, but they are so frequently injected to patients. So, we prepared lidocaine solid lipid microspheres (SLM) as long acting abdominal injection using spray drying method and evaluated drug entrapment, particle size, SEM, zeta potential and in vitro and in vivo drug release pattern, The particle sizes of SLM were 30∼100$\mu$m and it is enough to inject into abdominal tissue. The entrapment efficiency of SLM was over 95％ as spray drying method. Surfactant and PC decreased the burst effect by 20∼30％. In in vivo test, C-6 showed controlled release concentration profile in plasma for 8 days and C-5 sustained longer than we expected.

• YAKHAK HOEJI
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• v.40 no.4
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• pp.400-410
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• 1996

In oder to develop the controlled release of drugs from the suppositories, in vitro drug release and in vivo absorption in rabbits were investigated. Various suppo sitory forms with hollow cavities, into which drugs in the form of fine powder or solid dispersion system(SDS) could be placed, were utilized. The oleaginous Witepsol H-15 (WH-15) as a base, and indomethacin (IDM) of a very slightly soluble drug and propranolol-HCL (PPH) of a very soluble drug were employed as model drugs. The in vitro drug release showed that the cumulative release amount of PPH from PPH-(methylcellulose) MC-SDS and PPH-(ethylcellulose) EC-SDS hollow type suppositories reached 40% and 12% in 6 hrs,respectively. On the other hand, the drug release for a conventional suppository was 80% in 6 hrs. For the IDM suppositories,the cumulative drug release from IDM-(polyvinylpyrrolidone) PVP-SDS hollow type suppositories reached 99% in 24 hrs, whereas that from a conventional suppository reached 85%. An in vivo experiment with rabbits showed that IDM-PVP-SDS hollow type suppository delayed the absorption of IDM, significantly. The $t_{max},\;C_{max}\;and\;AUC_{0{\to}8}$ of IDM-PVP-SDS suppository were 60 min, 12.12${\mu}g$/ml and 2657${\mu}g$/ml/min, respectively. The $t_{max},\;C_{max}\;and\;AUC_{0{\to}8}$ of controlled group were 20 min, 15.49${\mu}g$/ml and 2190${\mu}g$/ml/min, respectively.

• Journal of Pharmaceutical Investigation
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• v.26 no.4
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• pp.299-308
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• 1996

In order to develop the controlled release of a drug from the suppsitories, in vitro drug release and in vivo absorption in rabbits were investigated. Various suppository forms with hollow cavities, into which drugs in the form of fine powder or solid dispersion system(SDS) could be placed, were utilized. The polyvinyl alcohol(PVA) hydrogel as a base, and propranolol HCl(PPH) as a model drug were employed. In vitro drug dissolution studies showed that the dissolved amounts(%) of PPH from PPH-methylcellulose(MC)-SDS and PPH-ethylcellulose(EC)-SDS reached 100% and 63% in 4.5-hours, respectively. In the relative strength test for PVA hydrogel, PVA hydrogel became harder and more rigid when the number of freezing-thawing cycles and the ratio of PVA 2000 were increased. In vitro drug release profile revealed that the release rate(%) of PPH from PPH-EC-SDS and PPH-MC-SDS hollow type suppositories were sustained. The release amount(%) of PPH from PPH-EC-SDS hollow type suppositories was not affected by storage time, but since the use of hydrophilic MC made PPH diffuse into the hydrogel after it absorbed the water of base, the various release patterns were appeared as the storage time went by. In vivo absorption experiments with rabbits showed that PPH-EC-SDS(PPH : EC=1:3) hollow type suppository delayed the absorption of PPH, significantly. The $C_{max}$, $AUC_{0{\rightarrow}8}$ and MRT of PPH powder hollow type suppository were $196.37{\pm}5.63\;ng/ml$, 1105.26 ng/ml/min and 8.66 min, respectively. The $C_{max}$, $AUC_{0{\rightarrow}8}$ and MRT of PPH-EC-SDS(PPH : EC=1:3) were $91.30{\pm]14.14\;ng/ml$, 554.69 ng/ml/min, 235.99 min, respectively.

• Journal of Pharmaceutical Investigation
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• v.41 no.5
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• pp.279-288
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• 2011

The Dexamethasone (DEX) loaded chitosan microspheres were prepared by thermal denaturation and chemical cross-linking method using a dierent concentration of glutaraldehyde as chemical cross-linking agent. The prepared microspheres were evaluated for the percentage of Drug Loading (DL), Encapsulation Efficiency (EE) and surface morphology by Scanning Electron Microscopy (SEM). DL and EE were found to be maximum range of 10.0 to 10.79 % and 58.19 to 64.73 % respectively. The SEM Photographs of the resultant microspheres exhibited fairly smooth surfaces and predominantly spherical in appearance. In addition, Fourier Transform Infrared Spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC) shown that there was no interaction between the drug and polymer. In vitro and in vivo release studies revealed that the release of dexamethasone was sustained and extended up to 63 days and effectively controlled by the extent of cross-linking agent. Non-clinical parameters such as paw volume, hematological parameters like Erythrocyte Sedimentation Rate (ESR), Paced Cell Volume (PCV), Total Leucocytes Count (TLC), Hemoglobin (Hb), Differential Cell Count (DCC) were investigated in Fruend's Complete Adjuvant (FCA) induced arthritic rats. Radiology and histopathological studies were also performed in order to evaluate the therapeutic efficacy of the DEX-loaded microspheres in extenuating the rat arthritic model.

• YAKHAK HOEJI
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• v.40 no.1
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• pp.52-58
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• 1996

Solvent fractions were prepared from traditional herbal drugs which of methanol extracts inhibited $CCl_4$-induced cytotoxicity in primary cultured rat hepatocytes and c ontinuously assayed their effects. Ethylacetate and n-buthanol fractions from Cibotii Rhizoma and chloroform fraction from Gelatina Nigra inhibited the release of LDH and GPT from $CCl_4$-treated hepatocytes, respectively. Water fraction (WAR) among solvent fractions from Astragali Radix showed the most potent inhibitory effect on the release of GOT or GPT by treatment with $CCl_4$. All of solvent fractions prepared from Eucommiae Cortex had no effect on $CCl_4$-induced cytotoxicity. Chloroform and ethylacetate fractions from Rehmanniae Radix Preparata increased the release of GPT from $CCl_4$-treated hepatocytes. n-Hexan, chloroform or ethylacetate fraction from 5 herbal drugs increased the release of LDH, GOT or GPT from normal hepatocytes at the dose of 1.Omg/ml. Administration of WAR suppressed the elevation of GOT, ALP activities and MDA contents in the serum as well as in the liver tissue of $CCl_4$-intoxicated rats. Based on these results, isolation of antihepatotoxic substances from WAR is under the process.

• Advances in Traditional Medicine
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• v.7 no.1
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• pp.51-64
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• 2007

Mucus is an aqueous gel complex with a constitution of about 95% water, high molecular weight glycoprotein (mucin), lipid, salts etc. Mucus appears to represent a significant barrier to the absorption of some compounds. Natural mucoadhesive agent was isolated and purified from the aqueous extract of the seeds of prosopis pallida (PP). Formulated tablet with the isolated material by wet granulation method. Some natural edible substances are in consideration for candidates as mucoadhesive agents to claim more effective controlled drug delivery as an alternative to the currently used synthetic mucoadhesive polymers. Subjected the materials obtained from natural source i.e. PP and standard synthetic substance, sodium carboxymethyl cellulose for evaluation of mucoadhesive property by various in vitro and in vivo methods. Through standard dissolution test and a model developed with rabbit, evaluated in vitro controlled release and bioadhesive property of theophylline formulation. Mucoadhesive agent obtained from PP showed good mucoadhesive potential in the demonstrated in vitro and in viνo models. The results suggest that the mucoadhesive agent showed controlled release properties by their application, substantially. In order to assess the gastrointestinal transit time in vivo, a radio opaque X-ray study performed in healthy rabbit testing the same controlled release formulation with and without bioadhesive polymer. Plasma levels of theophylline determined by the HPLC method and those allowed correlations to the in vitro mucoadhesive study results. Better correlation found between the results in different models. PP may acts as a better natural mucoadhesive agent in the extended drug delivery system.

• Biomedical Science Letters
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• v.13 no.3
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• pp.175-182
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• 2007

In vitro ciprofloxacin (CFX)-release study and bioassay using microorganisms were performed to estimate the retention of the antimicrobial activity of the CFX-incorporated central venous catheters (CFX-CVCs). The release experiments were carried out under the optional CFX-release conditions to mimic the in vivo environment. The release of CFX experienced an initial burst followed by a slow and steady matrix-diffusion controlled release. The 1.0CP (polyurethane catheter containing 1.0% (w/w) of CFX) under dynamic condition showed a near zero-order CFX release profile, which is beneficial for the long-tenn antimicrobial activity. The modified Kirby-Bauer method was performed employing S. aureus and E. coli to evaluate the retention of antimicrobial activity of the catheters retrieved from the release experiments. The 1.0CP showed the long-term antimicrobial activity (${\geq}\;21$ days) against both S. aureus and E. coli. These results indicate that 1.0CP is useful as a long-tenn indwelling CVC.

• Journal of Pharmaceutical Investigation
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• v.32 no.3
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• pp.199-207
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• 2002

In order to develop a sustained release formulation of bovine somatotropin (BST), which has been used to increase the body weight of oxen or the milk production of dairy cows, poly(D,L-lactide-co-glyceride)(PLGA) microspheres were made by W/O/W multiple emulsification method and solvent extraction method. Physical properties including particle size, drug entrapment, drug release, protein denaturation, and in vivo body weight increase in rats were characterized. The size of the microspheres was increased as the molecular weight of PLGA increased. When Span 65 and stearic acid during preparation were added, the size was decreased but the amount of surface protein was increased, resulting in a high loading efficiency, with fast release of BST from the microspheres. Aggregation or fragmentation of BST by SDS-PAGE during microsphere preparation and drug release study was not observed. Body weight of Sprague-Dawley's male rats was significantly increased after subcutaneous administrations of BST-loaded PLGA microspheres. There was a good correlation between in vivo weight gain and in vitro release rate of microspheres. PLGA microspheres with a high surface protein ratio could be a good candidate for the sustained delivery of BST.

• Journal of Photoscience
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• v.9 no.2
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• pp.427-429
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• 2002

We studied iron release from ferritin by irradiating the visible light, and then followed ferritin-mediated lipid peroxidation in the rod outer segment (ROS) fraction of the porcine retina. In the presence of several phosphorus compounds such as ADP and ATP, iron release from ferritin at pH 7.0 could be induced by irradiation of the visible light to the reaction mixtures. Furthermore, iron release from ferritin in the presence of ADP depended on the incubation time and the visible light irradiation. Moreover, we investigated lipid peroxidation level in the ROS fraction by two independent assay systems including the thiobarbituric acid (TBA) and ferrous oxidation/xylenol orange (FOX) methods. The visible light induced ferritin-mediated lipid peroxidation in the ROS fraction in time- and irradiance-dependent manners. In the dark condition, iron release and lipid peroxidation were not observed. Iron release from ferritin by irradiating the visible light may play an important role in the etiology of phototoxic injuries in vivo.

• YAKHAK HOEJI
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• v.44 no.5
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• pp.424-431
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• 2000

A biopharmaceutics drug classification system for correlation between in vitro dissolution and in vivo bioavailability is proposed based on recognizing that drug dissolution and gastrointestinal permeability are the fundamental parameters controlling the rate and extent of drug absorption. The objective of this study was to assess whether in vitro dissolution profiles of immediate-release beta-blocker tablets can be correlated with intestinal membrane permeability and/or in vivo bioavailability In vitro dissolution of the beta-blocker tablets was examined using KP VII Apparatus II methods at various pH. Intestinal membrane permeability was determined in vitro using the diffusion chamber method. Bioavailablity parameters were cited from literatures. The dissolution profiles did not accurately represent the in vivo bioavailablity However there were good correlations between intestinal membrane permeability and log P (noctanol/buffer). The correlations obtained in this study indicated that in vitro diffusion chamber method could be used to predict intestinal absorption in vivo.