• YAKHAK HOEJI
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• v.44 no.4
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• pp.308-314
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• 2000

Logarithmic transformation of pharmacokinetic parameters is routinely used in bioequivalence studies based on pharmacokinetic and statistical grounds by the United States Food and Drug Administration (FDA), European Committee for Proprietary Medicinal Products (CPMP), and Japanese National Institute of Health and Science (NIHS). Although it has not yet been recommended by the Korea Food and Drug Administration (KFDA), its use is becoming increasingly necessary in order to harmonize with international standards. In the present study, statistical procedures for the analysis of a bioequivalence based on the log transformation and a related SAS procedure were demonstrated in order to aid the understanding and application. The AUC parameters used in this demonstration were taken from the previous bioequivalence study for two aceclofenac tablets, which were performed in a single-dose crossover design. Analysis of variance (ANOVA), statistical power to detect 20% difference between the tablets, minimum detectable difference and confidence intervals were all assessed following log-transformation of the data. Bioequivalence of two aceclofenac tablets was then estimated based on the guideline of FDA. Considering the international effort for harmaonization of guidelines for bioequivalence tests, this approach may require a further evaluation for a future adaptation in the Korea Guidelines of Bioequivalence Tests (KGBT).

• Journal of Pharmaceutical Investigation
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• v.20 no.2
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• pp.89-95
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• 1990

Ethylcellulose-PEG 4000 film coated on core tablets was investigated as a potential drug delivery system for the controlled release of chlorpheniramine maleate (CPM). The kinetic analysis of the release data indicated that CPM release followed a diffusion-controlled model, where the quantity released per unit area is proportional to the square root of time. The effect of the film composition, CPM concentration, plasticizer concentration and CPM solubility on the release characteristics were examined. The release rate constant increased as CPM concentration increased. It also increased as the PEG 4000 content in the film increased above 10%(w/w), however, it decreased as the PEG 4000 content increased in the concentration range below 10%(w/w). The release rate constant was not affected by the coated weight on the core tablet. The film-coated tablets which contain CPM only in the coated film layer seemed to be a potential oral drug delivery system for the controlled release of CPM.

• Analytical Science and Technology
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• v.37 no.2
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• pp.114-122
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• 2024

A transmission Raman spectroscopy-based quantitative model, which can analyze the content of a drug product containing naproxen sodium as its active pharmaceutical ingredient (API), was developed. Compared with the existing analytical method, i.e., high-performance liquid chromatography (HPLC), Raman spectroscopy exhibits high test efficiency owing to its shorter sample pre-treatment and measurement time. Raman spectroscopy is environmentally friendly since samples can be tested rapidly via a nondestructive method without sample preparation using solvent. Through this analysis method, rapid on-site analysis was possible and it could prevent the production of defective tablets with potency problems. The developed method was applied to the assays of the naproxen sodium of coated tablets that were manufactured in commercial scale and the content of naproxen sodium was accurately predicted by Raman spectroscopy and compared with the reference analytical method such as HPLC. The method validation of the new approach was also performed. Further, the specificity, linearity, accuracy, precision, and robustness tests were conducted, and all the results were within the criteria. The standard error of cross-validation and standard error of prediction values were determined as 0.949 % and 0.724 %, respectively.

• Journal of Pharmaceutical Investigation
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• v.32 no.3
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• pp.223-229
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• 2002

Metformin is an oral antihyperglycemic agent used in the therapy of noninsulin-dependent diabetes mellitus and does not cause hypoglycemia at the therapeutic dose. Its mechanism of action may involve an increased binding of insulin to its receptors and glucose uptake at the post-receptor level. The purpose of the present study was to evaluate the bioequivalence of two metformin tablets, Glucophage (Daewoong Pharmaceutical Co., Ltd.) and Glycomin (Ilsung Pharmaceuticals Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The metformin release from the two metformin tablets in vitro was tested using KP VII Apparatus II method with various dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty four normal male volunteers, $23.75{\pm}1.96$ years in age and $68.77{\pm}10.41\;kg$ in body weight, were divided into two groups with a randomized $2{\times}2$ cross-over study. After one tablet containing 500 mg as metformin was orally administered, blood was taken at predetermined time intervals and the concentrations of metformin in serum were determined using HPLC with UV detector. Besides, the dissolution profiles of two metformin tablets were very similar at 떠1 dissolution media. The pharmacokinetic parameters such as $AVC_t,\;C_{max}\;and\;T_{max}$ were calculated. The ANOVA test was performed for the statistical analysis of the logarithmically transformed $AVC_t\;and\;C_{max}$, untransformed $T_{max}$. The results showed that the differences in $AVC_t,\;C_{max}\;and\;T_{max}$ between two tablets based on the Glucophage were 0.09%, 6.09% and -8.22%, respectively. There were no sequence effects between two tablets in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(1.25) $(e.g.,\;log(0.94){\sim}log(1.09)\;and \;log(1.01){\sim}log(1.15)$\;for\;AVC_t\;and\;C_{max},\;respectively)$, indicating that Glycomin tablet is bioequivalent to Glucophage tablet.

• Journal of Pharmaceutical Investigation
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• v.32 no.2
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• pp.119-125
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• 2002

A rapid, selective and reproducible high-performance liquid chromatographic method has been developed for the determination of terazocin in human plasma. Terazocin plus the internal standard, prazocin hydrochloride, were extracted from alkalified plasma with tert-butylmethyl ether, back-extracted into 0.05% phosphoric acid. Fifty ${\mu}l-portions$ of extract were injected onto a octadecylsilane column and eluted with a mixture of acetonitrile, water and triethylamine (30 : 70 : 0.1 v/v, adjusted to pH 5.0 with dilute phosphoric acid) at a flow rate of 1.0 ml/min. The fluorescence intensity of column eluents was monitored at excitation wavelength of 250 nm and emission wavelength of 370 nm. No interference peaks were observed. The practical limit of quantitation was 5 ng/ml for terazocin. The average intraday and interday coefficients of variation were 4.15 and 3.54%, respectively. Also intraday and interday precisions over the range $5{\sim}60\;ng/ml$ were $0.49{\sim}2.92\;and\;0.38{\sim}5.12%$, respectively. The bioequivalence of two terazosin tablets, the $Hytrine^{\circledR}$ (Il Yang Pharmaceutical Co., Ltd.) and the $Teratonin^{\circledR}$ (Sam-A Pharmaceutical Co., Ltd.), was evaluated according to the guideline of Korea Food and Drug Administration (KFDA). Sixteen healthy male volunteers $(24.6{\pm}2.0\;years\;old)$ were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 2 mg of terazosin was orally administered, blood was taken at predetermined time intervals and the concentration of terazosin in plasma was determined with a HPLC method using spectrofluorometric detector. AUC was calculated by the linear trapezoidal method. $C_{max}\;and\;T_{max}$ were compiled from the plasma drug concentration-time data. Analysis of variance (ANOVA) was utilized for the statistical analysis of the parameters. The results showed that the differences in $AUC_t,\;C_{max}\;and\;T_{max}$ between the two preparations were 0.21 %, 5.53% and 8.82%, respectively. The powers $(1-{\beta})\;for\;AUC_t,\;C_{max}\;and\;T_{max}$ were >99%, 97.49%, and 33.26%, respectively. Minimum detectable differences $({\Delta},\;%)\;at\;{\alpha}=0.1\;and\;1-{\beta}=0.8$ and the 90% confidence intervals were all less than ${\pm}20%$ except for $T_{max}.\;AUC_t\;and\;C_{max}$ met the criteria of KDFA for bioequivalence, indicating that $Teratonin^{circledR}$ tablets are bioequivalent to $Hytrine^{circledR}$ tablets.

• Journal of Pharmaceutical Investigation
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• v.32 no.2
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• pp.127-133
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• 2002

Levosulpiride is the 1evo-enantiomer form of racemic sulpiride, a benzamide derivative selectively inhibiting dopaminergic $D_2$ receptors at the trigger zone both in the central nervous system and in the gastrointestinal tract. The purpose of the present study was to evaluate the bioequiva1ence of two levosulpiride tablets, Levopride (SK Pharmaceutical Co., Ltd.) and Levopid (Dae Won Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The levosulpiride release from the two levosulpiride 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 and water). Twenty eight normal male volunteers, $23.82{\pm}3.26$ years in age and $69.13{\pm}8.58$ 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 levosulpiride was orally administered, blood was taken at predetermined time intervals and the concentrations of levosulpiride in serum were determined using HPLC method with fluorescence detector. The dissolution profiles of two levosulpiride 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 logarithmically transformed $AUC_t\;and\;C_{max}$ and untransformed $T_{max}$. The results showed that the differences in $AUC_t,\;C_{max}\;and\;T_{max}$ between two tablets based on the Levopride were -1.17%, 1.20% and -1.09%, respectively. There were no sequence effects between two tablets in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(1.25) $(e.g.,\;log(0.93){\sim}log(1.07)\;and\;log(0.90){\sim}log(1.14)\;for\;AUC_t\;and\;C_{max}$, respectively). The 90% confidence interval using untransformed data was within ${\pm}20%$ $(e.g.,\;-19.47{\sim}16.20\;for\;T_{max})$. All parameters met the criteria of KFDA guideline for bioequivalence, indicating that Levopid tablet is bioequivalent to Levopride tablet.

• Journal of Pharmaceutical Investigation
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• v.39 no.2
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• pp.133-139
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• 2009

The purpose of the present study was to evaluate the bioequivalence of two pioglitazone HCl tablets, $Actos^{TM}$, tablets (Lilly Korea. Ltd., Korea) as a reference drug and $Piros^{TM}$, tablets (Reyon Pharm. Co., Ltd., Korea) as test drug, according to the guideline of Korea Food and Drug Administration (KFDA). Twenty-four healthy male Korean volunteers received one tablet containing pioglitazone HCl 15 mg in a $2{\times}2$ crossover study. There was a one-week washout period between the doses. Plasma concentrations of pioglitazone were monitored for over a period of 36 hr after administration by using a high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). The area under the plasma concentration-time curve from time zero to 36 hr ($AUC_{0-36hr}$), maximum plasma drug concentration ($C_{max}$) and time to reach $C_{max}$ ($T_{max}$) were complied from the plasma concentration-time data. Analysis of variance (ANOVA) test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_{0-36hr}$ and $C_{max}$. The 90% confidence intervals of the $AUC_{0-36hr}$ ratio and the $C_{max}$ ratio for $Piros^{TM}$/$Actos^{TM}$. were log 0.8753-log 1.1286 and log 0.8669-log 1.1734, respectively. These values were within the acceptable bioequivalence intervals of log 0.80-log 1.25, recommended by KFDA. In all of these results, we concluded that the $Piros^{TM}$. tablet was bioequivalent to the $Actos^{TM}$. tablet, based on the rate and extent of absorption.

• Journal of Conservation Science
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• v.33 no.4
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• pp.241-254
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• 2017

The Stone Guardian and Memorial Tablets from the Muryeong Royal Tomb are composed of the same kind of plutonic igneous rocks, the so-called hornblendite. Color of the rocks show greenish gray, and both of them occurred with medium-grained granular texture. The rock-forming minerals composed mainly of amphibole and plagioclase. Magnetic susceptibility of the Stone Guardian is 0.15 to 0.63 (mean $0.42{\times}10^{-3}SI\;unit$), the King's Stone Memorial Tablet is 0.11 to 0.38 (mean $0.24{\times}10^{-3}SI\;unit$) and the Queen's Stone Memorial Tablet ranges from 0.10 to 0.33 (mean $0.18{\times}10^{-3}SI\;unit$). The rocks of the artifacts are hard to find in the Gongju area. Large scaled out crop of hornblendite is not distributed, but found in many places that the form of dike. The lithology and occurrences indicate that the artifacts are made of plutonic rock rather than dike. Reddish brown and pale brown contaminants, are also distributed on the surface of the Stone Guardian and Memorial Tablets. The reddish brown color is due to Fe oxide, and the pale brown color occurs due to the elution of Ca. The reddish brown contaminants are influenced by the internal components of the rock and oxidation of burial iron accessories. In contrast, the pale brown contaminants are considered to have flown from the carbonate materials used in the Royal Tomb, with a little added Fe oxide. Physical and chemical deterioration operate intricately in the Stone Guardian and Memorial Tablets. Physical deterioration is extremely rare and chemical deterioration is stable except for a part of the Stone Guardian and the front of the Queen Stone Memorial Tablet.

• YAKHAK HOEJI
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• v.54 no.5
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• pp.348-353
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• 2010

The dissolution test method and an analytical procedure by HPLC were developed and validated for viquidil hydrochloride capsules and alibendol tablets. These drugs were not yet characterized by the dissolution specifications in Korean Pharmaceutical Codex. So, with each reference and test drugs, we did the preliminary and standard experiments based on the Korean Pharmacopeia Guideline of dissolution testing for solid oral dosage forms. The dissolution test for viquidil hydrochloride capsules was carried out under sink conditions as follows: dissolution medium water, paddle rotation speed 50 rpm and vessel volume 900 ml. More than 90% of its label amount was released within 30 min in this method. Also the dissolution test for alibendol tablets was carried out under sink conditions as follows: dissolution medium water, paddle rotation speed 100 rpm and vessel volume 900 ml. More than 90% of its label amount was released within 45 min in this method. The dissolution samples were analyzed with a precise and accurate HPLC method. The developed dissolution test showed specificity, linearity, precision and accuracy within the acceptable range. The dissolution testing method described above was adequate for the purpose and may be proposed as a pharmacopeial standard to assess the performance of viquidil hydrochloride capsules and alibendol tablets.

• Biomolecules & Therapeutics
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• v.6 no.2
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• pp.219-224
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• 1998

The bioequivalence of two clarithromvcin products was evaluated with 16 normal male volunteers (age 23-28 yr, body weight 57.5-75.517g) following single oral dose. Test product was ReYon Clarithromycin tablets (ReYon Pharm. Corp., Korea) and reference product was Klarici $d_{R}$ tablets (Abbott Korea). Both products contain 250 mg of clarithromucin. One tablet of the test or the reference product was administered to the volunteers, respectively, by randomized two period cross-over study (2$\times$2 Latin square method). The determination of clarithromycin was accomplished using a modified agar well diffusion bioassay. As a result of the assay validation, the quantification of clarithromycin in human serum by this technique was possible down to 0.03$\mu$g/ml using 100$\mu$l of serum. The coefficient of variation (C.V.) was less than 10%. Average drug concentrations at each sampling time and pharmacokinetic parameters calculated were not significantly different between two products P>0.05); the area under the curve to last sampling time (24 hr) (AU $Co_{24hr}$ (8.10$\pm$ 1.26 vs 8.22$\pm$ 1.627g . hr/ml), AUC from time zero to infinite (AU $Co_{\infty}$) (8.61 $\pm$ 1.28 vs 8.84$\pm$ 1.71 $\mu$g . hr/ml), maximum plasma concentration ( $C_{msx}$) (0.87$\pm$0.22 vs 0.88$\pm$0.19 $\mu$g/ml) and time to maximum plasma concentration ( $T_{max}$) (2.69 $\pm$0.48 vs 2.56$\pm$ 0.51 hr). The differences of mean AU $Co_{24h}$, $C_{msx}$ and $T_{msx}$ between the two products (1.44, 1.39, and 4.65%, respectively) were less than 20%. The power (1-$\beta$) and treatment difference ($\Delta$) for AU $Co_{24hr}$, and $C_{max}$ were more than 0.8 and less than 0.2, respectivly. Although the power for $T_{max}$ was under 0.8, $T_{max}$. of the two products was not significantly different each other (p>0.05). These results suggest that the bioavailability of ReYon Clarithromycin tablets is not significantly different from that of Klarici $d_{R}$ tablets. Therefore, two products are bioequivalent based on the current results. results.sults.sults.s.s.s.s.s.s.s.