• Journal of Pharmaceutical Investigation
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• 제32권2호
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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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• 제32권2호
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• pp.135-140
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• 2002

Cefadroxil is a semi-synthetic cephalosporin active against many Gram-positive and Gram-negative bacteria. The drug has been used for the treatment of the urinary and respiratory tract infections when caused by susceptible strains of the designated microorganism. The purpose of the present study was to evaluate the bioequivalence of two cefadroxil capsules, Duricef (Bo Ryung Pharmaceutical Co. Ltd.) and Hanacef (Korean Pharmaceutical Co. Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The cefadroxil release from the two cefadroxil capsules 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 four normal male volunteers, $21.58{\pm}2.43$ years in age and $70.74{\pm}10.29$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one capsule containing 500 mg as cefadroxil was orally administered, blood was taken at predetermined time intervals and the concentrations of cefadroxil in serum were determined using HPLC with UV detector. The dissolution profiles of two cefadroxil capsules were very similar at all dissolution media. 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 capsules based on the Duricef were 0.05%, -5.29% and 4.53%. There were no sequence effects between two capsules in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(1.25) $(e.g.,\;log(0.95){\sim}log(1.05)\;and\;log(0.87){\sim}log(1.02)$ for $AUC_t\;and\;C_{max}$, respectively). The 90% confidence interval using untransformed data was within ${pm}20%$ $(e.g.,\;-6.75{\sim}15.74\;for\;T_{max})$. All parameters met the criteria of KFDA guideline for bioequivalence, indicating that Hanacef capsule is bioequivalent to Duricef capsule.

• Journal of Pharmaceutical Investigation
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• 제36권2호
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• pp.143-148
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• 2006

Finasteride $[N-(1, 1-dimethylethyl)-3-oxo-4-aza-5{\alpha}-androst-1-ene-17{\beta}-carboxamide]$ is a 4-aza-3-oxosteroidal inhibitor of human $5{\alpha}-reductase$. The purpose of the present study was to evaluate the bioequivalence of two finasteride tablets, $Proscar^{\circledR}$ (MSD Korea Ltd.) and Procare (Hana Pharm. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of finasteride from the two finasteride formulations in vitro was tested using KP VIII Apparatus II method with various dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty six healthy male subjects, $23.7\;{\pm}\;2.24$ years in age and $67.2\;{\pm}\;8.55\;kg$ in body weight, were divided into two groups and a randomized $2\;{\time}\;2$ cross-over study was employed. After two tablets containing 5 mg as finasteride was orally administered, blood samples were taken at predetermined time intervals and the concentrations of finasteride in serum were determined using HPLC with UV detector. The dissolution profiles of two formulations were similar in all tested dissolution media. 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 $AUC_t,\;C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, $Proscar^{\circledR}$, were 6.39, 4.65 and -13.9% 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 0.800 to log 1.25 $(e.g.,\;log\;0.990{\sim}log\;1.14\;and\;log\;0.977{\sim}log\;1.13 for\;AUC_t\;and\;C_{max},\;respectively)$. Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Procare tablet was bioequivalent to $Proscar^{\circledR}$ tablet.

• Journal of Pharmaceutical Investigation
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• 제41권5호
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• pp.317-322
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• 2011

Sertraline HCl, (1S-cis)-4-(3, 4-dichloro-phenyl)-1, 2, 3, 4-tetrahydro-N-methyl-l-naphthalenamine hydrochloride, is a potent and selective serotonin reuptake inhibitor which is used in the treatment of depression and obsessivecompulsive disorders. The purpose of the present study was to evaluate the bioequivalence of two sertraline HCl tablets, Traline tablet (Myungin Pharm. Co. Ltd.) and Zoloft$^{(R)}$ tablet (Pfizer Inc.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The in vitro release of sertraline from the two sertraline HCl formulations was tested using KP VIII Apparatus II method with various dissolution media. Twenty four healthy Korean male volunteers, $23.50{\pm}1.74$ years in age and $64.09{\pm}7.10\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ crossover study was employed. After a single tablet containing 50 mg as sertraline HCl was orally administered, blood samples were taken at predetermined time intervals and the concentrations of sertraline in serum were determined using an online columnswitching HPLC method with UV/Vis detection. The dissolution profiles of two formulations were similar in all tested dissolution media. The pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated, and computer programs (Equiv Test and K-BE Test) were utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and un-transformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, Zoloft$^{(R)}$ tablet, were 0.04, 3.26 and -1.29% 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 log0.8 to log1.25. Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Traline tablet was bioequivalent to Zoloft$^{(R)}$ tablet.

• Journal of Pharmaceutical Investigation
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• 제41권2호
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• pp.117-123
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• 2011

Loxoprofen sodium, a 2-phenylpropionate non-steroidal anti-inflammatory drug (NSAID), has marked analgesic and antipyretic activities and relatively weak gastrointestinal ulcerogenicity. The purpose of the present study was to evaluate the bioequivalence of two loxoprofen sodium tablets, Hana loxoprofen sodium tablet (Hana Pharm. Co., Ltd.) and Dongwha Loxonin$^{(R)}$ tablet (Dongwha Pharm. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The in vitro release of loxoprofen from the two loxoprofen sodium formulations was tested using KP IX Apparatus II method with various dissolution media. Twenty four healthy Korean male volunteers, $22.83{\pm}1.862$ years in age and $69.92{\pm}9.14$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ crossover study was employed. After a single tablet containing 60 mg as loxoprofen sodium was orally administered, blood samples were taken at predetermined time intervals and the concentrations of loxoprofen in serum were determined using a online column-switching HPLC method with UV/Vis detection. The dissolution profiles of two formulations were similar in all tested dissolution media. The pharmacokinetic parameters such as $AUC^t$, $C_{max}$ and $T_{max}$ were calculated, and computer programs (Equiv Test and K-BE Test 2002) were utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and un-transformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, Dongwha Loxonin$^{(R)}$ tablet, were 2.03, 2.99 and -9.49% 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 log0.8 to log1.25 (e.g., log0.9831~log1.0535 and log0.9455~log1.1386 for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Hana loxoprofen sodium tablet was bioequivalent to Dongwha Loxonin$^{(R)}$ tablet.

• Journal of Pharmaceutical Investigation
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• 제40권1호
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• pp.51-57
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• 2010

Losartan potassium, 2-butyl-4-chloro-1-[p-(o-1H-tetrazol-5-ylphenyl)benzyl]imidazole-5-methanol mono-potassium salt, is a new class of antihypertensive agents, and is an antagonist in angiotensin receptor. The purpose of the present study was to evaluate the bioequivalence of two Losartan potassium tablets, Cozaar tablet (MSD Pharmaceutical Co., Ltd.) and Losata tablet (Kyung Dong Pharmaceutical Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of losartan from the two losartan potassium formulations in vitro was tested using KP VIII Apparatus II method with various dissolution media. Twenty eight healthy male subjects, $23.86{\pm}1.80$ years in age and $67.27{\pm}6.60\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After a single tablet containing 50 mg as losartan potassium was orally administered, blood samples were taken at predetermined time intervals, and the concentrations of losartan in serum were determined using HPLC with fluorescence detector. The dissolution profiles of two formulations were similar in all tested dissolution media. The pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated, and Equiv Test/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, Cozaar, were -2.70%, 1.45% and 2.31% 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 0.8852~log 1.0655 and log 0.8319~log 1.2342 for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Losata tablet was bioequivalent to Cozaar tablet.

• 약학회지
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• 제52권4호
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• pp.299-305
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• 2008

Gabapentin, 1-(aminomethyl) cyclohexaneacetic acid, is a amino acid derivative, and is clinically effective in the treatment of neuropathic pain and partial seizures of epilepsy as a complementary therapy. The purpose of the present study was to evaluate the bioequivalence of two gabapentin tablets, $Neurontin^{R}$ tablet 800 mg (Pfizer Pharmaceuticals Co., Ltd.) and Gabapenin tablet 800 mg (Hanmi Pharm. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of gabapentin from the two gabapentin formulations in vitro was tested using KP VIII Apparatus II method with 0.06 M HCI dissolution media. Twenty six healthy male subjects, $23.85{\pm}2.24$ years in age and $69.40{\pm}11.11$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ crossover study was employed. After a single tablet containing 800 mg as gabapentin was orally administered, blood samples were taken at predetermined time intervals and the concentrations of gabapentin in serum were determined using HPLC with fluorescence detector. The dissolution profiles of two formulations were similar in the tested dissolution media. 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 $AUC_{t}$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, $Neurontin^{R}$, were 1.28%, 0.63% and 0.62% 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., $log0.9097{\sim}log1.1598$ and $log0.8919{\sim}log1.1262$ for $AUC_{t}$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Gabapenin tablet 800 mg was bioequivalent to $Neurontin^{R}$ tablet 800 mg.

• 약학회지
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• 제57권3호
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• pp.205-212
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• 2013

Dissolution test has been performed to control drug quality and to predict in vivo drug release profile of solid dosage forms, so there's a drift towards setting dissolution test instead of disintegration test. However, some solid dosage forms in Korea Pharmaceutical Codex (KPC) are not established the dissolution test yet, so these monographs are necessary to set the specification of dissolution test. In this study, we developed the specification and test method of dissolution test for itopride hydrochloride tablets and tiropramide hydrochloride tablets which are not established the dissolution test yet. According to the "Manual for Guideline Application for Validation of Analytical Procedures" and "Guidelines on Specification of Dissolution test for Oral dosage form" of Korean Pharmacopoeia (KP), we validated and established each development method. Based on the preliminary dissolution profile, we set the dissolution condition(paddle apparatus, pH 1.2 media, 50 rpm). For this condition, we performed the main dissolution test to determine the specification (45 min, 85%). Finally, we validated each analytical method by specificity, linearity, accuracy and precision. These developed methods will be included the next supplement of KPC and also contributed to the quality control of medicines.

• 한국임상약학회지
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• 제20권3호
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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.

• 한국임상약학회지
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• 제20권3호
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• pp.235-241
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• 2010

Bambuterol hydrochloride, dimethylcarbamic acid 5-[2-(1,1-dimethylethyl)amino-1-hydroxyethyl]-1,3-phenylene ester hydrochloride, is the prodrug of active ${\beta}_2$-adrenergic metabolite terbutaline. The purpose of the present study was to evaluate the bioequivalence of two bambuterol hydrochloride tablets, $Bambec^{(R)}$ tablet 10 mg (Yuhan Co., Ltd.) and Bambucol tablet 10 mg (Sam Chun Dang Pharm. Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). In vitro release of bambuterol from two bambuterol hydrochloride formulations was tested using KP VIII Apparatus II method with various dissolution media. Twenty eight healthy male Korean volunteers, $23.86{\pm}1.65$ years in age and $68.98{\pm}9.58$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After two tablets containing 10 mg as bambuterol hydrochloride were orally administered, blood samples were taken at predetermined time intervals, and the concentrations of bambuterol in serum were determined using column switching HPLC with UV detector. The dissolution profiles of two formulations were similar in all tested dissolution media. The pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated, and ANOVA test with 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, $Bambec^{(R)}$, were -8.10%, -3.82% and 12.65% 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 (i.e., log 0.8093~log 1.0302 and log 0.8564~log 1.1280 for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Bambucol tablet 10 mg was bioequivalent to $Bambec^{(R)}$ tablet 10 mg.