bioequivalence

2384's picture

Comparative fasting bioavailability of two clopidogrel formulations in healthy Mediterranean volunteers: an in vitro–in vivo correlation

Journal Title, Volume, Page: 
rug Design, Development and Therapy 24(9):2359-65 · April 2015
Year of Publication: 
2015
Authors: 
Abdel naser Zaid
Department of Pharmacy, Faculty of Medicine and health sciences, An-Najah National University, Nablus, Palestine
Current Affiliation: 
Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
Rowa Ramahi
Department of Pharmacy, Faculty of Medicine and health sciences, An-Najah National University, Nablus, Palestine
Rana Bustami
Pharmaceutical Research Unit, Amman, Jordan
Ayman Mousa
R&D Department, Middle East Pharmaceutical Industries Co Ltd, Riyadh, Saudi Arabia
Sewar Khasawneh
Pharmaceutical Research Unit, Amman, Jordan
Preferred Abstract (Original): 
OBJECTIVE:
The aim of this study was to evaluate the bioequivalence of two drug products, generic clopidogrel bisulfate 75 mg film-coated tablets versus the reference Plavix(®) clopidogrel bisulfate 75 mg film-coated tablets.
METHODS:
Bioequivalence of tablets was tested by comparisons against the reference brand product in accordance with the requirements of the Declaration of Helsinki, the current Good Clinical Practice Guidelines, and the International Conference on Harmonization.
RESULTS:
The relationship between concentration and peak area ratio was found to be linear within the range 24.500-1,836.600 pg/mL for clopidogrel. The correlation coefficient (r) was always greater than 0.99 during the course of the validation. Statistical comparison of the main pharmacokinetic parameters showed no significant difference between test and reference. The point estimates (ratios of geometric mean) were 104.122%, 104.184%, and 109.091% for areas under the plasma concentration-time curve (AUC) AUC0-last, AUC0-∞, and peak plasma concentration C max, respectively. These pharmacokinetic parameter values of clopidogrel and its main metabolite lie within the bioequivalence limit (80%-125%) specified by the US Food and Drug Administration and the European Medicines Agency.
CONCLUSION:
The tested drug product was bioequivalent to the reference drug under fasting conditions and had the same safety profile, which is important to achieve equivalent therapeutic effect with the reference.
saedkh's picture

Formulation and Comparative Bioavailability of 2 Ciprofloxacin Sustained Release Tablets

Journal Title, Volume, Page: 
Arzneimittelforschung 2012; 62(07): 319-323 DOI: 10.1055/s-0032-1311609
Year of Publication: 
2012
Authors: 
Zaid AN
Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
Qaddomi A
Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
Khammash S.
Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
Current Affiliation: 
Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
Preferred Abstract (Original): 

BACKGROUND AND THE PURPOSE OF THE STUDY:

The aim of this study is to formulate and evaluate the quality of ciprofloxacin (CAS number: 85721-33-1) sustained release tablet (Ciprocare®XR) 1 000 mg ciprofloxacin (test formulation) by comparing its pharmacokinetic parameters with Cipro®XR sustained release tablet (reference formulation). For this purpose ciprofloxacin SR tablets were developed using the 2-layer method. To assess the quality of the produced sustained release tablets a randomized, 2-way, crossover, bioequivalence study was performed in 24 healthy, male volunteers. The selected Middle Eastern volunteers were divided into 2 groups of 12 subjects. One group was treated with the reference formulation and the other one with the test formulation, with a cross-over after a drug washout period of 7 days. Blood samples were collected at fixed time intervals and Ciprofloxacin concentrations were determined by a validated HPLC assay method. The pharmacokinetic parameters AUC0-48, AUC0-∞, Cmax, Tmax, Ke and T1/2 were determined for both sustained release tablets and were compared statistically to evaluate the bioequivalence between the 2 formulations of ciprofloxacin, using the statistical model recommended by the FDA. The analysis of variance (ANOVA) did not show any significant difference between the 2 formulations and 90% confidence intervals (CI) fell within the acceptable range for bioequivalence. According to the obtained results it was concluded that the test and reference formulations are bioequivalent, since they exhibit comparable pharmacokinetic parameters.

saedkh's picture

Formulation and Bioequivalence of Two Valsartan Tablets After a Single Oral Administration

Journal Title, Volume, Page: 
Sci Pharm. Mar 2011; 79(1): 123–135. Published online Nov 20, 2010. doi: 10.3797/scipharm.1009-01
Year of Publication: 
2010
Authors: 
Abdel Naser Zaid
Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
Rita Cortesi
Department of Pharmaceutical Sciences, University of Ferrara, ViaFossato di Mortara, 17–19, 44100. Ferrara, Italy
Aiman Qaddomi
Pharmacare Ltd. Beitunia, P.O. Box: 677, Ramallah, Palestine
Saed Khammash
Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
Current Affiliation: 
Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
Preferred Abstract (Original): 

The aim of this study is to assess the quality of Valzan® tablet (160 mg, valsartan immediate release test formulation) by comparing its pharmacokinetic parameters with Diovan® tablet (160 mg, valsartan reference formulation). Valzan® tablets were prepared according to a dry granulation method (roll compaction). To assess the bioequivalence of Valzan® tablets a randomized, two-way, crossover, bioequivalence study was performed in 24 healthy male volunteers. The selected volunteers were divided into two groups of 12 subjects. One group was treated with the reference formulation (Diovan®) and the other one with the generic Valzan®, with a cross-over after the drug washout period of 14 days. Blood samples were collected at fixed time intervals and valsartan concentrations were determined by a validated HPLC assay method. The pharmacokinetic parameters AUC0–48, AUC0–∞, Cmax, Tmax, Ke and T1/2 were determined for both the tablets and were compared statistically to evaluate the bioequivalence between the two brands of valsartan, using the statistical model recommended by the FDA. The analysis of variance (ANOVA) did not show any significant difference between the two formulations and 90% confidence intervals (CI) fell within the acceptable range for bioequivalence. Based on this statistical evaluation it was concluded that the test tablets (Valzan®) is well formulated, since it exhibits pharmacokinetic profile comparable to the reference brand Diovan®.

2384's picture

Interchangeability of Two 500 mg Amoxicillin Capsules With One ‎‎1000 mg Amoxicillin Tablet After A Single Oral Administration

Journal Title, Volume, Page: 
Indian J Pharm Sci.;72(4):414-20
Year of Publication: 
2010
Authors: 
Zaid AN
College of Pharmacy, An-Najah National University, Nablus, Palestine
Current Affiliation: 
Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
Sweileh W
Cortesi R
Kort J
Preferred Abstract (Original): 

The aim of the study was to evaluate if two capsules (Amoxil(®) capsules, 500 mg/capsule) and one tablet (Amoxicare(®) tablets, 1000 mg/tablet) of amoxicillin have similar bioequivalence parameters. For this purpose a randomized, two-way, crossover, bioequivalence study was performed in 24 healthy, male volunteers, divided into two groups of 12 subjects each. One group was treated with the reference standard (Amoxil(®)) and the other one with the generic tablet Amoxicare(®), with a crossover after a wash-out period of 7 days. Blood samples were collected at fixed time intervals and amoxicillin was determined by a validated HPLC method. The pharmacokinetic parameters AUC(0-8), AUC(0-∞), C(max), T(max), K(e) and T(1/2) were determined for both formulations and statistically compared to evaluate the bioequivalence between the two brands of amoxicillin, using the statistical model recommended by the FDA. C(max) and AUC(0-∞) were statistically analyzed using analysis of variance (ANOVA); no statistically significant difference was observed between the two formulations. The 90% confidence intervals between the mean values of C(max) and AUC(0-∞) fall within the FDA specified bioequivalent limits (80-125%) suggesting that the two products are bioequivalent and the two formulations are interchangeable. Based on these findings it was concluded that the practice of interchangeability between the above formulations to achieve better patient compliance could be followed without compromising the extent of amoxicillin absorption.

2384's picture

Formulation and Comparative Bioavailability of 2 Ciprofloxacin ‎Sustained Release Tablets

Journal Title, Volume, Page: 
Arzneimittelforschung ; 62(07): 319-323
Year of Publication: 
2012
Authors: 
Zaid AN
College of Pharmacy, An-Najah National University, Nablus, Palestine
Current Affiliation: 
Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
Qaddomi A
Pharmacare Ltd. Beitunia, Ramallah, Palestine
Khammash S
College of Pharmacy, An-Najah National University, Nablus, Palestine
Preferred Abstract (Original): 

The aim of this study is to formulate and evaluate the quality of ciprofloxacin (CAS number: 85721-33-1) sustained release tablet (Ciprocare®XR) 1 000 mg ciprofloxacin (test formulation) by comparing its pharmacokinetic parameters with Cipro®XR sustained release tablet (reference formulation). For this purpose ciprofloxacin SR tablets were developed using the 2-layer method. To assess the quality of the produced sustained release tablets a randomized, 2-way, crossover, bioequivalence study was performed in 24 healthy, male volunteers. The selected Middle Eastern volunteers were divided into 2 groups of 12 subjects. One group was treated with the reference formulation and the other one with the test formulation, with a cross-over after a drug washout period of 7 days. Blood samples were collected at fixed time intervals and Ciprofloxacin concentrations were determined by a validated HPLC assay method. The pharmacokinetic parameters AUC0-48, AUC0-∞, Cmax, Tmax, Ke and T1/2 were determined for both sustained release tablets and were compared statistically to evaluate the bioequivalence between the 2 formulations of ciprofloxacin, using the statistical model recommended by the FDA. The analysis of variance (ANOVA) did not show any significant difference between the 2 formulations and 90% confidence intervals (CI) fell within the acceptable range for bioequivalence. According to the obtained results it was concluded that the test and reference formulations are bioequivalent, since they exhibit comparable pharmacokinetic parameters.

shawahna's picture

Very Rapid Dissolution Is Not Needed To Guarantee Bioequivalence for Biopharmaceutics Classification System (BCS) I Drugs

Journal Title, Volume, Page: 
J Pharm Sci. 2010 Feb;99(2):621-5
Year of Publication: 
2010
Authors: 
H. Kortejärvi
Research and Development, Orion Pharma, Espoo, Finland
A. Koski
Research and Development, Orion Pharma, Espoo, Finland
R. Shawahna
Research and Development, Orion Pharma, Espoo, Finland
Current Affiliation: 
Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
J. Malkki
Research and Development, Orion Pharma, Espoo, Finland
K. Ojala
Research and Development, Orion Pharma, Espoo, Finland
M. Yliperttula
Research and Development, Orion Pharma, Espoo, Finland
Preferred Abstract (Original): 
Currently, the EMEA, FDA, and WHO as regulatory authorities accept rapidly dissolving (>85% dissolved in 30 min) biopharmaceutics classification system (BCS) I drug products for biowaiver candidates. In the draft EMEA guideline the requirement has been set tighter, that is, the drug product should be very rapidly dissolving (>85% dissolved in 15 min) to be eligible for a biowaiver. Pharmacokinetic modeling of 32 BCS I drugs was performed to demonstrate that very rapid dissolution is not necessary to guarantee bioequivalence for them. Rapid dissolution and similar dissolution profiles are sufficient criteria for all BCS I drugs.
Waleed Sweileh's picture

Interchangeability of Two 500 Mg Amoxicillin Capsules with One 1000 Mg Amoxicillin Tablet After a Single Oral Administration

Journal Title, Volume, Page: 
Indian J Pharm Sci., 72(4): 414–420
Year of Publication: 
2010
Authors: 
W Sweileh
College of Pharmacy, An-Najah National University, Nablus, Palestine
Current Affiliation: 
College of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
AN Zaid
College of Pharmacy, An-Najah National University, Nablus, Palestine
R Cortesi
Department of Pharmaceutical Sciences, Ferrara University, Ferrara
J Kort
Pharmacare Chemical and Cosmetics, Ramallah, Palestine
Preferred Abstract (Original): 

The aim of the study was to evaluate if two capsules (Amoxil® capsules, 500 mg/capsule) and one tablet (Amoxicare® tablets, 1000 mg/tablet) of amoxicillin have similar bioequivalence parameters. For this purpose a randomized, two-way, crossover, bioequivalence study was performed in 24 healthy, male volunteers, divided into two groups of 12 subjects each. One group was treated with the reference standard (Amoxil®) and the other one with the generic tablet Amoxicare®, with a crossover after a wash-out period of 7 days. Blood samples were collected at fixed time intervals and amoxicillin was determined by a validated HPLC method. The pharmacokinetic parameters AUC0-8, AUC0-∞, Cmax, Tmax, Ke and T1/2 were determined for both formulations and statistically compared to evaluate the bioequivalence between the two brands of amoxicillin, using the statistical model recommended by the FDA. Cmax and AUC0-∞ were statistically analyzed using analysis of variance (ANOVA); no statistically significant difference was observed between the two formulations. The 90% confidence intervals between the mean values of Cmax and AUC0-∞ fall within the FDA specified bioequivalent limits (80-125%) suggesting that the two products are bioequivalent and the two formulations are interchangeable. Based on these findings it was concluded that the practice of interchangeability between the above formulations to achieve better patient compliance could be followed without compromising the extent of amoxicillin absorption.

2384's picture

Formulation and Bioequivalence of Two Valsartan Tablets after a Single Oral Administration

Journal Title, Volume, Page: 
Sci. Pharm. 2011; 79: 123–135
Year of Publication: 
2011
Authors: 
Abdel Naser ZAID
Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
Current Affiliation: 
Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
Rita CORTESI
Department of Pharmaceutical Sciences, University of Ferrara, ViaFossato di Mortara, 17–19, 44100. Ferrara, Italy
Aiman QADDOMI
Pharmacare Ltd. Beitunia, P.O. Box: 677, Ramallah, Palestine
Saed KHAMMASH
College of Pharmacy, An-Najah National University, P.O. Box: 7, Nablus, Palestine
Preferred Abstract (Original): 

The aim of this study is to assess the quality of Valzan® tablet (160 mg, valsartan immediate release test formulation) by comparing its pharmacokinetic parameters with Diovan® tablet (160 mg, valsartan reference formulation). Valzan® tablets were prepared according to a dry granulation method (roll compaction). To assess the bioequivalence of Valzan® tablets a randomized, two-way, crossover, bioequivalence study was performed in 24 healthy male volunteers. The selected volunteers were divided into two groups of 12 subjects. One group was treated with the reference formulation (Diovan®) and the other one with the generic Valzan®, with a cross-over after the drug washout period of 14 days. Blood samples were collected at fixed time intervals and valsartan concentrations were determined by a validated HPLC assay method. The pharmacokinetic parameters AUC0–48, AUC0–∞, Cmax, Tmax, Ke and T1/2 were determined for both the tablets and were compared statistically to evaluate the bioequivalence between the two brands of valsartan, using the statistical model recommended by the FDA. The analysis of variance (ANOVA) did not show any significant difference between the two formulations and 90% confidence intervals (CI) fell within the acceptable range for bioequivalence. Based on this statistical evaluation it was concluded that the test tablets (Valzan®) is well formulated, since it exhibits pharmacokinetic profile comparable to the reference brand Diovan®.

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