• Korean Journal of Clinical Pharmacy
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• v.9 no.1
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• pp.44-48
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• 1999

The bioequivalence of two aceclofenac tablets was evaluated in 14 normal volunteers (age $21\sim29$ yrs) following oral administration. The test product was 'Apental tablet' made by Asia Pharmaceutical Co. and the reference was 'Airtal tablet' made by Daewoong Pharmaceutical Co. After one tablet containing 100 mg aceclofenac was administered, blood was taken at predetermined time intervals and the concentration of the drug in plasma was quantitated with an HPLC method. AUC, $C_{max}\;and\;T_{max}$ were calculated and statistically analyzed for the bioequivalence of the two products. The results showed that the differences in AUC, $C_{max}\;and\;T_{max}$ between two products were $4.23\%,\;2.15\%\;and\;0\%$, respectively. The powers for AUC,$\;C_{max}\;and\;T_{max}\;were\;>90\%,\;>90\%\;and\;85.8\%$, respectively. Confidence intervals were within $\pm20\%$ for three parameters. All of these parameters met the criteria of KFDA for bioequivalence, indicating that 'Apental tablet' is bioequivalent to "Airtal tablet".(Kor. J. Clin. Pharm. 1999; 9(1): 44-48)

• Journal of Pharmaceutical Investigation
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• v.31 no.4
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• pp.289-295
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• 2001

Carvedilol is an antihypertensive and antianginal compound that combines nonselective beta-adrenoceptor blocking and vasodilation properties and is devoid of intrinsic sympathomimetic activity. The purpose of the present study was to evaluate the bioequivalence of two carvedilol tablets, $Dilatrend^{TM}$ (Chong Kun Dang Pharmaceutical Co., Ltd.) and $Carvelol^{TM}$ (Dae Won Pharmaceutical Co., Ltd.), according to the prior and revised guidelines of Korea Food and Drug Administration (KFDA). The carvedilol release from the two carvedilol tablets in vitro was tested using KP VII Apparatus II method with various different kinds of dissolution media (pH 1.2, 4.0, 6.8 buffer solution, water and blend of PSB80 into water). Eighteen normal male volunteers, $24.22{\pm}1.86$ years in age and $64.81{\pm}4.56\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 25 mg of carvedilol was orally administered, blood was taken at predetermined time intervals and the concentrations of carvedilol in serum were determined using HPLC method with fluorescence detector. The dissolution profiles of two carvedilol tablets were very similar at all dissolution media. Besides, the pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using non-transformed and logarithmically transformed $AUC_t$ and $C_{max}$. The results showed that the differences in $AUC_t$, $C_{max}$ and $T_{max}$ between two tablets based on the $Dilatrend^{TM}$ were 2.23%, -2.00% and 0.00%, respectively. Minimum detectable differences $({\Delta})$ at ${\alpha}=0.05$ and $1-{\beta}=0.8$ were less than 20% (e.g., 13.55% and 17.61% for $AUC_t$ and $C_{max}$, respectively). The powers $(l-{\beta})$ at ${\alpha}=0.05$, ${\Delta}=0.2$ for $AUC_t$ and $C_{max}$ were 98.08% and 88.81%, respectively. The 90% confidence intervals were within ${\pm}20%$ (e.g., $-5.69{\sim}10.16$ and $-12.30{\sim}8.30$ for $AUC_t$ and $C_{max}$, respectively). There were no sequence effect between two tablets in logarithmically transformed $AUC_t$ and $C_{max}$. The 90% confidence intervals using logarithmically transformed were within the acceptance range of log(0.8) to log(1.25) (e.g., $0.95{\sim}1.11$ and $0.89{\sim}1.09$ for $AUC_t$ and $C_{max}$, respectively). Two parameters met the criteria of prior and revised KFDA guideline for bioequivalence, indicating that $Carvelol^{TM}$ tablet is bioequivalent to $Dilatrend^{TM}$ tablet.

• Journal of the Korean Society for Library and Information Science
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• v.17
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• pp.11-47
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• 1989

This study intends to examine the background and the procedure of the carving of the tablets of the second edition of Dae-Jang-Mock­Lock(재조대장목록). the time and the route of the moving of the tablets. into Haein-sa, and the contents and the system of it. This study is mainly based on the second edition of Dae-Jang-Mock-Lock. But the other closely related materials such as restored first. edition of the Dae- Jang-Mock-Lock, Koryo Sin-Jo-Dae-Jang-Byeol-Lock (고려신조대장교정별록). Kae-Won-Seok-Kyo-Lock (개원석교록). Sok-Kae­Won-Seok-Kyo-Lock (속개원석교록). Jeong-Won-Sin-Jeong-Seok-Kyo­Lock(정원신정석교록), Sok-Jeong-Won-Seok-Kyo-Lock(속정원석교록), Dea-Jung-Sang-Bu-Beob-Bo-Lock(대중상부법보록), and Kyeong-Woo-Sin-Su-Beob-Bo-Lock(경우신수법보록), are also analysed and closely examined. The results of this study can be summarized as follows: 1. The second edition of Tripitaka Koreana(고려대장경) was carved for the purpose of defending the country from Mongolia with the power of Buddhism, after the tablets of the first edition in Buin-sa(부이사) was destroyed by fire. 2. In 1236. Dae-Jang-Do-Gam(대장도감) was established, and the preparation for the recarving of the tablets such as comparison between the content, of the first edition of Tripitalk Koreana, Gal-Bo-Chik-Pan-Dae­Jang-Kyeong and Kitan Dae- Jang-Kyeong, transcription of the original copy and the preparation of the wood, etc. was started. 3. In 1237 after the announcement of Dae-Jang-Gyeong-Gak-Pan-Gun­Sin-Gi-Go-Mun(대장경핵판군신석고문), the carving was started on a full scale. And seven years later (1243), Bun-Sa-Dae-Jang-Do-Gam(분사대장도감) was established in the area of the South to expand and hasten the work. And a large number of the tablets were carved in there. 4. It took 16 years to carve the main text and the supplements of the second edition of Tripitaka Koreana, the main text being carved from 1237 to 1248 and the supplement from 1244 to 1251. 5. It can be supposed that the tablets of the second edition of Tripitaka Koreana, stored in Seon-Won-Sa(선원사), Kang-Wha(강화), for about 140 years, was moved to Ji-Cheon-Sa(지천사), Yong-San(용산), and to Hae-In-Sa(해인사) again, through the west and the south sea and Jang-Gyeong-Po(장경포), Go-Ryeong(고령), in the autumn of the same year. 6. The second edition of Tripitaka Koreana was carved mainly based on the first edition, comparing with Gae-Bo-Chik-Pan-Dae-Jang-Kyeong(개보판대장경) and Kitan Dae-Jang-Kyeong(계단대장경). And the second edition of Dae-Jang-Mock-Lock also compiled mainly based on the first edition with the reference to Kae-Won-Seok-Kyo-Lock and Sok-Jeong-Won-Seok-Kyo-Lock. 7. Comparing with the first edition of Dae-Jang-Mock-Lock, in the second edition 7 items of 9 volumes of Kitan text such as Weol-Deung­Sam-Mae-Gyeong-Ron(월증삼매경론) are added and 3 items of 60 volumes such as Dae-Jong-Ji-Hyeon-Mun-Ron(대종지현문논) are substituted into others from Cheon chest(천함) to Kaeng chest(경함), and 92 items of 601 volumes such as Beob-Won-Ju-Rim-Jeon(법원주임전) are added after Kaeng chest. And 4 items of 50 volumes such as Yuk-Ja-Sin-Ju-Wang-Kyeong(육자신주왕경) are ommitted in the second edition. 8. Comparing with Kae-Won-Seok-Kyo-Lock, Cheon chest to Young chest (영함) of the second edition is compiled according to Ib-Jang-Lock(입장록) of Kae-Won-Seok-Kyo-Lock. But 15 items of 43 vol­umes such as Bul-Seol-Ban-Ju-Sam-Mae-Kyeong(불설반주삼매경) are ;added and 7 items of 35 volumes such as Dae-Bang-Deung-Dae-Jib-Il­Jang-Kyeong(대방등대집일장경) are ommitted. 9. Comparing with Sok-Jeong-Won-Seok-Kyo-Lock, 3 items of the 47 volumes (or 49 volumes) are ommitted and 4 items of 96 volumes are ;added in Caek chest(책함) to Mil chest(밀함) of the second edition. But the items are arranged in the same order. 10. Comparing with Dae- Jung-Sang-Bo-Beob-Bo-Lock, the arrangement of the second edition is entirely different from it. But 170 items of 329 volumes are also included in Doo chest(두함) to Kyeong chest(경함) of the second edition, and 53 items of 125 volumes in Jun chest(존함) to Jeong chest(정함). And 10 items of 108 volumes in the last part of Dae-Jung-Sang-Bo-Beob-Bo-Lock are ommitted and 3 items of 131 volumes such as Beob-Won-Ju-Rim-Jeon(법원주임전) are added in the second edition. 11. Comparing with Kyeong-Woo-Sin-Su-Beob-Bo-Lock, all of the items (21 items of 161 volumes) are included in the second edition without ;any classificatory system. And 22 items of 172 volumes in the Seong­Hyeon-Jib-Jeon(성현집전) part such as Myo-Gak-Bi-Cheon(묘각비전) are ommitted. 12. The last part of the second edition, Joo chest(주함) to Dong chest (동함), includes 14 items of 237 volumes. But these items cannot be found in any other former Buddhist catalog. So it might be supposed as the Kitan texts. 13. Besides including almost all items in Kae-Won-Seok-Kyo-Lock and all items in Sok-Jeong-Won-Seok-Kyo-Lock, Dae-Jung-Sang-Bo­Beob-Bo-Lock, and Kyeong-Woo-Sin-Su-Beob-Bo-Lock, the second edition of Dae-Jang-Mock-Lock includes more items, at least 20 items of about 300 volumes of Kitan Tripitaka and 15 items of 43 volumes of traditional Korean Tripitake that cannot be found any others. Therefore, Tripitaka Koreana can be said as a comprehensive Tripitaka covering all items of Tripitakas translated in Chinese character.

• Analytical Science and Technology
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• v.24 no.6
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• pp.519-526
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• 2011

Chemometrics using near-infrared (NIR) and Raman spectroscopy have found significant uses in a variety quantitative and qualitative analyses of pharmaceutical products in complex matrixes. Most of the pharmaceutical can be measured directly with little or no sample preparation using these spectroscopic methods. During pharmaceutical manufacturing process, analytical techniques with no or less sample preparation are very critical to confirm the quality. This study showed NIR and Raman spectroscopy with principal component analysis (PCA) was very effective for the blending processing control. It is of utmost importance to evaluate critical parameters related to quality of products during pharmaceutical processing. The blending is confirmed by off-line determination of active pharmaceutical ingredient (API) by a conventional method such as high performance liquid chromatography (HPLC) and UV spectroscopy. These analytical methods are time-consuming and ineffective for real time control. This study showed the possibility for the determination of blend uniformity end-point of CR tablets with the use of both NIR and Raman spectroscopy. The samples were acquired from six positions during blending processing with U-type blender from 0 to 30 min. Using both collected NIR and Raman spectral data, principal component analysis (PCA) was used to follow the uniformity of blending and finally determine the end-point. The variation of homogeneity of six samples during blending was clearly found and blend uniformity end-point was successfully confirmed in the domains of principal component (PC) scores.

• Journal of Pharmaceutical Investigation
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• v.31 no.2
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• pp.125-130
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• 2001

Bucillamine is a novel cysteine derivative with two free intramolecular sulfhydryl groups, and has a preventive and therapeutic effect on adjuvant arthritis, suggesting its antirheumatic action. With respect to the effect on the immune system, bucillamine-exerted such immunoregulating actions are to nomalize an excessive reduction or acceleration in immune reaction. It is useful not only in patients with early stage of rheumatoid arthritis (RA) but also in those with active RA retained for more than 10 years. The purpose of the present study was to evaluate the bioequivalence of two bucillamine tablets, $Rimatil^{TM}$ (Chong Kun Dang Pharmaceutical Co., Ltd.) and $Bucilin^{TM}$ (Kuhn Il Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Eighteen normal male volunteers, $23.67{\pm}2.09$ years in age and $65.03{\pm}6.73\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After three tablets containing 100 mg of bucillamine per tablet were orally administered, blood was taken at predetermined time intervals and the concentrations of bucillamine in serum were determined using GC/MS with mass selective detector. Pharmacokinetic parameters such as $AUC_t$, $C_{max}\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters. The results showed that the differences in $AUC_t$, $C_{max}\;and\;T_{max}$ between two tablets were -0.29%, -3.20% and 8.22%, respectively, when calculated against the $Rimatil^{TM}$ tablet. The powers $(1-{\beta})$ for $AUC_t\;and\;C_{max}$ were 84.31 % and 91.16%, respectively. Minimum detectable differences $({\Delta})$ at ${\alpha}=0.10$ and $1-{\beta}=0.8$ were less than 20% (e.g., 18.58% and 16.51% for $AUC_t\;and\;C_{max}$, respectively). The 90% confidence intervals were within ${\pm}20%$ (e.g.,$-12.77{\sim}12.20$ for $AUC_t$ and $-14.30{\sim}7.90$ for $C_{max}$). Two parameters met the criteria of KFDA for bioequivalence, indicating that $Bucilin^{TM}$ tablet is bioequivalent to $Rimatil^{TM}$ tablet.

• Korean Journal of Clinical Pharmacy
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• v.20 no.3
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• pp.255-261
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• 2010

Cefprozil is a broad-spectrum oral beta-lactam cephalosporin consisting of cis- and trans-isomeric mixture whose ratio is approximately 90:10. Cefprozil is used to treat certain infections caused by bacteria such as bronchitis and ear, skin, and throat infections. The purpose of the present study was to evaluate the bioequivalence of two cefprozil tablets, $Cefzil^{(R)}$ tablet 250 mg (BMS Pharmaceutical Korea., Ltd.) and Procezil tablet 250 mg (Hanmi Pharm. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The in vitro release of cefprozil from the two cefprozil formulations were tested using KP VIII Apparatus I method with water dissolution media. Thirty five healthy male subjects, $24.00{\pm}1.53$ years in age and $69.77{\pm}9.99$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After four tablets containing 1000 mg as cefprozil were orally administered, blood samples were taken at predetermined time intervals and the concentrations of cefprozil in serum were determined using HPLC/UV detector. The dissolution profiles of two formulations were similar in water tested dissolution media. The pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ on the basis of total-cefprozil were calculated, and computer program (K-BE Test 2002) was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, $Cefzil^{(R)}$ tablets, were -0.81%, -3.00% and -6.83% for $AUC_t$, $C_{max}$ and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g., log 0.9515~log 1.0454 and log 0.9613~log 1.0465 for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Procezil tablet was bioequivalent to $Cefzil^{(R)}$ tablet.

• Journal of Pharmaceutical Investigation
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• v.31 no.1
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• pp.57-62
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• 2001

Azelastine, a phthalazinone derivative, is an antiallergic agent which demonstrates histamine $H_1-receptor$ antagonist activity and also inhibits histamine release from mast cells following antigen and non-antigen stimuli. Thus, azelastine may be useful in the management of both asthma and allergic disorders. The purpose of the present study was to evaluate the bioequivalence of two azelastine hydrochloride tablets, $Azeptin^{TM}$ (Bu Kwang Pharmaceutical Co., Ltd.) and $Azela^{TM}$ (Kyung Dong Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Eighteen normal male volunteers, $22.44{\pm}2.01$ years in age and $61.99{\pm}6.18\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After two tablets containing 1 mg of azelastine hydrochloride per tablet were orally administered, blood was taken at predetermined time intervals and the concentrations of azelastine in serum were determined using HPLC with fluorescence detector. Pharmacokinetic parameters such as $AUC_t$, $C_{max}\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters. The results showed that the differences in $AUC_t$, $C_{max}\;and\;T_{max}$ between two tablets were -6.45%, -2.60% and -7.14%, respectively, when calculated against the $Azeptin^{TM}$ tablet. The powers $(1-{\beta})$ for $AUC_t\;and\;C_{max}$ were 96.65% and 88.47%, respectively. Minimum detectable differences $({\Delta})$ at ${\alpha}=0.05$ and $1-{\beta}=0.8$ were less than 20% (e.g., 14.40% and 17.65% for $AUC_t\;and\;C_{max}$, respectively). The 90% confidence intervals were within ${\pm}20%$ (e.g., $-14.87{\sim}1.97$ and $-12.92{\sim}7.72$ for $AUC_t\;and\;C_{max}$, respectively). Two parameters met the criteria of KFDA for bioequivalence, indicating that $Azela^{TM]$ tablet is bioequivalent to $Azeptin^{TM}$ tablet.

• Journal of Pharmaceutical Investigation
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• v.40 no.5
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• pp.313-319
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• 2010

The objectives of this study were to evaluate the effect of formulation ingredients on the drug release and to optimize the novel sustained release matrix tablet formulations of bupropion hydrochloride. A three factor, three-level Box-Behnken design was used for the optimization procedure, with the amounts of PEO ($X_1$), citric acid ($X_2$) and Compritol 888 ATO ($X_3$) as the independent variables. The selected dependent variables were the cumulative percentage values of bupropion hydrochloride that had dissolved after 1, 4 and 8 hr. Various dissolution profiles of the drug from sustained release matrix tablets were obtained. Optimization was performed for $X_1$, $X_2$ and $X_3$ using the following target ranges; $30%{\leq}Y_1{\leq}45%$; $70{\leq}Y_2{\leq}85%$; $85%{\leq}Y_3{\leq}100%$. The optimized formulation for bupropion hydrochloride was achieved with 12.5% PEO ($X_1$), 2.5% citric acid ($X_2$) and 10% Compritol 888 ATO ($X_3$). The sustained release matrix tablets with the optimized formulation provided a release profile that was close to predicted values. In addition, the dissolution profiles of the sustained release matrix tablet with the optimized formulation were similar to those of the commercial product Wellbutrin$^{(R)}$ SR tablets ($f_2$=79.83).

• Korean Journal of Food Science and Technology
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• v.44 no.3
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• pp.274-279
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• 2012

The objective of this study was to develop oral matrix tablets for the sustained release of vitamin C. In this study hydroxypropyl methylcellulose (HPMC) has been utilized as an excipient, as it is one of the most widely used polymers, for use during long periods of time in formations. The vitamin C tablet formulation depends on the molecular weight and concentration of sustained-delivery in HPMC. Anti-oxidants have been added as a dissolution medium in order to prevent vitamin C degradation in water. The dissolution test was carried out in a distilled water medium, and the release model equation was applied to analyze the vitamin C release pattern. The results demonstrated that the release and lasting power of vitamin C tablets, containing HPMC, lasted for more than 12 h.

• Journal of Pharmaceutical Investigation
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• v.30 no.4
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• pp.241-246
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• 2000

To develop a sustained-release preparation containing ketorolac tromethamine, two sustained-release pellet formulations were evaluated with a pharmacokinetic study as compared with a conventional commercial tablets (10 mg $Tarasyn^{TM}$, Roche Korea Ltd.). Two sustained-release formulations were as follows; formulation A was composed of an inner layer containing 75% of drug coated with $Eudragit^{TM}$ RS 100 membrane and an outer layer containing 25% of drug mixed with $Eudragit^{TM}$ NE30D, and formulation B was composed of only an inner layer containing 100% of drug coated with $Eudragit^{TM}$ RS 100 membrane. The dissolution test was performed for two formulations. In case of conventional tablets, 2.5 mg of drug per a dose was administered orally into male Albino rabbit (2.0-2.3 kg of body weight) 3 times at intervals of 4 hours. In case of two sustained formulations, 7.5 mg of drug was administered once orally. Blood samples were withdrawn periodically after the administration, and the blood concentration was determined by HPLC. The conventional tablets showed very high peak-trough fluctuation between administered doses, but two sustained formulations showed less fluctuation. Formulation A with the loading dose showed the time to reach minimum effective concentration (MEC) i.e. the onset time was less than 20 min, while Formulation B had more than 1 hr of the onset time. Formulation A had the more constant plasma level than formulation B. However, formulation B had a time lag, so the plasma level was less than MEC for an initial period of 1 hr. In formulation A, the plasma level was maintained within the therapeutic window $(0.3-5\;{\mu}g/ml)$ for a long period. Formulation A was thought to be an ideal sustained-release formulation for ketorolac tromethamine oral delivery system.