Bioequivalence Assessment of Two Metformin Tablet Formulations Based on Urinary Excretion Data | Chapter 6 | Pharmaceutical Science: New Insights and Developments Vol. 6

Metformin is an oral antihyperglycemic agent that has been widely used in the management of type 2 diabetes mellitus for decades. Metformin is slowly absorbed after oral administration, and about 60% of an oral dose is excreted in the urine as unchanged drug within 24 h. The aim of the present study was to assess the bioequivalence of two metformin tablet formulations available in the Albanian market (product R as reference formulation and product T as test formulation).

 

The bioequivalence study was performed in eighteen healthy volunteers in a two-treatment, open, crossover design. A single oral dose (tablet containing 850 mg of metformin) of each product was administered with one-week washout period. Urinary concentrations of metformin were measured by high-performance liquid chromatography (HPLC) method, and pharmacokinetic parameters were estimated by urinary excretion data. The bioequivalence was determined by the following parameters: the cumulative amount of metformin excreted in the urine, the total amount of metformin excreted in the urine and the maximum urinary excretion rate of metformin.  Various pharmacokinetic parameters like peak excretion rate [(dDU/dt)max], time for peak excretion rate (tmax), cumulative amount (Dcum0-24), total amount of drug recovered from urine (Dcum0-\(\infty\)), elimination half-life (t1/2), and terminal elimination rate constant (kel), were calculated for both the formulations. Student’s t-test (paired) at a 5% level of significance was used for testing the differences between the mean values obtained from two treatments using statistical software STATA 13. Pharmacokinetic parameters generated for the two treatments were also compared for significant differences using ANOVA.

 

The average cumulative amounts of metformin excreted in urine after administration of Formulation R and Formulation T were found to be 346.3 mg (40.74% of dose) and 358.7 mg (42.2% of dose), respectively. The urinary excretion profiles of metformin up to 24 h for both formulations were found to be similar. Statistical comparison (90% confidence intervals of ratio) of pharmacokinetic parameters were in compliance with the international standards, indicating that products R and T can be considered bioequivalents and therefore interchangeable. The study also recommends conducting bioequivalence evaluations for other key medications listed in the national reimbursement list.

Author(s) Details

Eva Troja
Profarma Company, Albania.

 

Please see the book here:- https://doi.org/10.9734/bpi/psnid/v6/5695

A Detailed Review on LC-MS Methods for Assessing Febuxostat in Blood Plasma: Implications for Bioavailability and Bioequivalence Studies | Chapter 8 | Pharmaceutical Research: Recent Advances and Trends Vol. 9

Febuxostat (FBS) has emerged as a revolutionary treatment for hyperuricemia and gout. This comprehensive review provides a pioneering analysis of the instrumental role of Liquid Chromatography with Mass Spectrometry (LC-MS) in unravelling the bioavailability and bioequivalence of Febuxostat (FBS) in human plasma. Utilizing Febuxostat d9 and d7, along with other drugs as internal standards (IS), the review steers through the intricate view of pharmaceutical research, focusing on validation methods and the challenges presented by the complex pharmacokinetics of FBS. Unprecedented in its depth, the review aims to contribute valuable insights to the field by addressing the evolving paradigms in pharmaceutical analysis. FBS, a revolutionary advancement in the treatment of hyperuricemia and gout, takes centre stage, highlighting its pivotal role in contemporary therapeutic approaches. LC-MS develops as a cornerstone analytical method for studying FBS, offering unparalleled sensitivity and selectivity. The review delves into the sample preparation techniques, emphasizing the significance of protein precipitation and liquid-liquid extraction in extracting FBS from human blood plasma. LC-MS/MS, chosen for its exceptional sensitivity and specificity, becomes a focal point in FBS analysis, with IS employed to enhance accuracy. The optimization of chromatographic conditions, encompassing the careful selection of stationary and mobile phases, is highlighted as crucial for establishing a robust and reliable LC method, ensuring accuracy in pharmacokinetic studies of FBS. This review positions LC-MS as a cornerstone analytical technique, highlighting its critical role in the precise determination of Febuxostat in blood plasma, with significant implications for future bioavailability and bioequivalence studies. The study concluded that LC-MS's superiority in Febuxostat analysis set the stage for a future where pharmacokinetic studies become insightful, efficient, and transformative, shaping the future of pharmaceutical research.

 

Author (s) Details

 

Atchaya Chakravarthy
Department of Pharmaceutics, JSS College of Pharmacy, Ooty, Tamil Nadu–643 001, India.

 

Sanjuktha Vimal
Department of Biology, University of Toronto, Ontario–M5S3H2, Canada.

 

Please see the book here:- https://doi.org/10.9734/bpi/prrat/v9/3108

A Detailed Review on LC-MS Methods for Assessing Febuxostat in Blood Plasma: Implications for Bioavailability and Bioequivalence Studies | Chapter 8 | Pharmaceutical Research: Recent Advances and Trends Vol. 9

 

Febuxostat (FBS) has emerged as a revolutionary treatment for hyperuricemia and gout. This comprehensive review provides a pioneering analysis of the instrumental role of Liquid Chromatography with Mass Spectrometry (LC-MS) in unravelling the bioavailability and bioequivalence of Febuxostat (FBS) in human plasma. Utilizing Febuxostat d9 and d7, along with other drugs as internal standards (IS), the review steers through the intricate view of pharmaceutical research, focusing on validation methods and the challenges presented by the complex pharmacokinetics of FBS. Unprecedented in its depth, the review aims to contribute valuable insights to the field by addressing the evolving paradigms in pharmaceutical analysis. FBS, a revolutionary advancement in the treatment of hyperuricemia and gout, takes centre stage, highlighting its pivotal role in contemporary therapeutic approaches. LC-MS develops as a cornerstone analytical method for studying FBS, offering unparalleled sensitivity and selectivity. The review delves into the sample preparation techniques, emphasizing the significance of protein precipitation and liquid-liquid extraction in extracting FBS from human blood plasma. LC-MS/MS, chosen for its exceptional sensitivity and specificity, becomes a focal point in FBS analysis, with IS employed to enhance accuracy. The optimization of chromatographic conditions, encompassing the careful selection of stationary and mobile phases, is highlighted as crucial for establishing a robust and reliable LC method, ensuring accuracy in pharmacokinetic studies of FBS. This review positions LC-MS as a cornerstone analytical technique, highlighting its critical role in the precise determination of Febuxostat in blood plasma, with significant implications for future bioavailability and bioequivalence studies. The study concluded that LC-MS's superiority in Febuxostat analysis set the stage for a future where pharmacokinetic studies become insightful, efficient, and transformative, shaping the future of pharmaceutical research.

 

Author(s)details:-

 

Atchaya Chakravarthy (Master of Pharmacy)
Department of Pharmaceutics, JSS College of Pharmacy, Ooty, Tamil Nadu–643 001, India.

 

Sanjuktha Vimal (Majoring in Human Biology and Neuroscience)
Department of Biology, University of Toronto, Ontario–M5S3H2, Canada.

 

Please See the book here :- https://doi.org/10.9734/bpi/prrat/v9/3108

Concepts and Applications of Therapeutic Interchange in Bioequivalence and Generic Drugs | Chapter 10 | Novel Aspects on Pharmaceutical Research Vol. 8

In this episode, an outline detailing the ideas and applications of Therapeutic Interchange in Bioequivalence and Generic Drugs and to review scientific tests for marketing permission of generic device is presented. Bioequivalence studies are very important for the drug happening phase for two together new drugs and generic equivalents in the drug industry. Their description and the results of common products are a important part of the enrollment dossier offered by regulatory authorities. The significance of bioequivalence studies is increasing again due to the big growth of the production and devouring of generic merchandise. Bioequivalence studies play a key role in constituting interchangeability (therapeutic similarity) and substitution of general drugs, allowing pharmacists to substitute ruling class without requiring prescriber authorization. These studies contribute to cost-influence, improve community health outcomes and boost access to essential drugs.

Author(s) Details:

Eva Troja,
Profarma SH.A. Pharmaceutical Industry, Tirana, Albania.

Leonard Deda,
Department of Biomedical Sciences, Faculty of Medicine, University of Medicine, Tirana, Albania.

Please see the link here: https://stm.bookpi.org/NAPR-V8/article/view/11657

Validation of Sample Size Estimation by Bootstrapping Technique: Reference-scaled Average Bioequivalence Study| Chapter 1 | Current Overview on Pharmaceutical Science Vol. 1

 A new method was used and corroborated to estimate pivotal sample breadth from pilot study dossier and to establish Bioequivalence (BE) of Highly Variable Drugs (HVD), paroxetine, in human cases under fed environments using ghatti Gum as a rate ruling membrane, by remark scale design.Bootstrapping technique was selected to calculate the important sample size from pilot study dossier for HVD paroxetine. The reliability and confirmation of the method were proven in a semi copy three sequence (RRT, RTR, and TRR place T stand for test drug and R signify reference drug) cross-over BE study in 24 healthy issues under fed environments. Extended-Release (ER) matrix tablets were processed by wet granulation techniqueThe percentage of the Pharmacokinetic (PK) metric got from the bootstrapping technique afterwards log transformation was 1.04 for Cmax, 1.23 for AUCT, and 1.21 for AUCI accompanying corresponding capacity of the study which was more 80% from pilot study dossier simulation. The percentage of the PK metric acquired from the reference scaling design in the study was 1.00 for Cmax, 1.21 for AUCT, and 1.17 for AUCI. The upper limit of the Cmax, AUCT, and AUCI at 95% assurance limit was -0.143, -0.136, and -0.17, respectively.Reference climbing approaches were used to establish BE and test merchandise found BE with respect to the citation formulation, and therefore, we can conclude that the ghatti paste can be used as rate-reserved membrane in sure concentration to expand CR formulation of different drugs.

Author(s) Details:

V. Chandrakala,
Department of Pharmaceutics, East Point College of Pharmacy, Avalahalli, Bengaluru, Karnataka, India.

Utpal Kumar Sanki,
Department of Biostatistics, ICON Plc, Bengaluru, Karnataka, India.

Please see the link here: https://stm.bookpi.org/COPS-V1/article/view/8960

Comparison of Bioavailability and Pharmacokinetic of Two Formulations of Metformin 850 mg Tablets in Healthy Albanian Volunteers| Chapter 8 | Challenges and Advances in Pharmaceutical Research Vol. 9

 Aim: The aim concerning this study was to equate the bioavailability and pharmacokinetics of two formulations of metformin 850 mg tablets: GLUCOPHAGE® from Merck Santè laboratories (remark product) and METFORMINE from Profarma (test device) in healthy Albanian volunteers.Methods: An open label, randomized, two-ending, two-way crossover study was acted in twenty healthy signs up for a single 850 mg shot of metformin tablets. Pharmacokinetic parameters in the way that maximum plasma aggregation (Cmax), the area under the curve limited to a particular time (AUC0-14h), the field under the curve to infinite occasion (AUC0-∞), and the time to reach the maximum red body fluid concentration (Tmax) were persistent. The formulations were considered bioequivalent if the mathematical mean ratios of ln-transformed Cmax and AUC0-∞ principles were within the similarity range of 80%-125%.Results: Two Way ANOVA analysis of the ln-converted Cmax and AUC0-∞ indicated that nobody of the effects checked (formulation, ending, within and between-subject variances and continue) was statistically significant. The bioequivalence study results accompanied 90% confidence of breaks (90 % CI) for pharmacokinetic parameters like Cmax (91.8-115.6 %); AUC0-14 (90.4-109.2 %) AUC0-∞ (90.1-109.1%) and that were within the range of 0.80-1.25. A p advantage of less than 0.05 was deliberate statistically significant.Conclusion: The fruit METFORMINE (produced by Profarma Sh.a) is bioequivalent and, therefore, adequately interchangeable concerning AUC0-∞ and Cmax when compared accompanying the reference crop (GLUCOPHAGE®).

Author(s) Details:

Eva Troja,
University of Medicine, Albania.

Please see the link here: https://stm.bookpi.org/CAPR-V9/article/view/8678

Comparative Assessment of Clinical Pharmacokinetic and Bioequivalence Studies of Two Brands of Cephradine in Healthy Korean Volunteers Using HPLC Method | Chapter 9 | Trends in Pharmaceutical Research and Development Vol.4

 

The goal of our research was to compare the pharmacokinetics and evaluate the bioequivalence of
two brands of cephradine 500 mg capsules in 24 normal Korean volunteers. The plasma samples
were acquired at 13 time points for 8 h after administration. The concentrations of cephradine in
human plasma were measured by a high-performance liquid chromatography (HPLC). Isocratic
mobile phase which consisted of acetonitrile, methanol, and 20 mM potassium phosphate (15/5/80,
v/v/v, pH 3.48) was used to separate the analytical column cosmosil cholester (250 × 4.6 mm, 3 µm).
Analytes were detected in ultraviolet (260 nm). The novel analytical method was described assimple
sample preparation, a short retention time (less than 6 min) and makingit suitable for use in clinical
trials. Pharmacokinetic parameters, such asAUC0-t (20.54 vs 18.42 μg∙h/mL), AUC0-infinity (21.22 vs
19.14 μg∙h/mL), Cmax(12.69 vs 12.81 μg/mL), Tmax (1.22 vs 0.92 h), half-life (1.02 vs 1.13 h),
extrapolation(3.22% vs 3.75%), and Ke (0.73 vs 0.69 h-1) were determined for the reference and test
drugs in plasma. Pharmacokinetic parameters with a 90% confidence intervals were 87~95% for
AUC0-t and 91~115% for Cmax. They were satisfied within the bioequivalence range 80~125% of the
KFDA guidelines. Therefore, our HPLC method was well applied in a bioequivalence and
pharmacokinetic study of two formulations of cephadrine capsules (500 mg) in normal subjects.

Author (s) Details

Hyun-Jin Kim, PhD
Department of Pharmacology, Clinical Pharmacology Laboratory, Division of Molecular Therapeutics Development, Hanyang Biomedical Research Institute, College of Medicine, Hanyang University, Seoul, South Korea.

Ju-Seop Kang
Department of Pharmacology, Clinical Pharmacology Laboratory, Division of Molecular Therapeutics Development, Hanyang Biomedical Research Institute, College of Medicine, Hanyang University, Seoul, South Korea.

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Development of Validated LC-MS/MS Method for Pharmacokinetic and Bioequivalence Studies of Azelastine in Korean Healthy Volunteers | Chapter 5 | Current Topics in Medicine and Medical Research Vol. 1

The pharmacokinetic (PK) and bioequivalence (BE) studies of two formulations of azelastine (AZ) was carried out in 18 healthy male Korean volunteers according to a randomized crossover-design and were performed by a new validated liquid chromatography coupled to tandem mass spectrometry (LCMS/MS) method for quantitative analysis of plasma AZ. Subjects were given single dose of 2 tablets of 1 mg AZ of each formulation with 240 ml of water to subjects on 2 treatment days separated by one week washout period. After dosing, serial blood samples were collected for a period of 96 hours. AZ and the clomipramine (IS) were separated using a mobile phase of acetonitrile-5 mM NH4AC (8：2, v/v, pH=6.4) with flow rate of 0.25 ml/min over Luna C18 column. Analysis required 0.2 ml of plasma and involved a solid extraction with an Oasis HLB cartridge by on-line clean-up extraction automation system and then directly injected into HPLC with an API 3000 MS system by multiple reactions monitoring (MRM) mode. Several PK parameters (including AUC0-t, AUC0-infinity, Cmax, Tmax, T1/2 and Ke) were determined from the plasma concentration of AZ of both formulations. The AUC and Cmax was tested for BE after log-transformation of the data. The ionization was optimized using ESI (+) and selectivity was achieved by MS-MS analysis, m/z 112.0 and m/z 86.1 for AZ and IS, respectively. The calibration curves with r2＞0.999 were linear over a working range of 20∼2000 pg/ml. No endogenous compounds were found to interfere with the analysis. The inter- and intra-day accuracy was in the ranges of 89.9∼109.3% and precision of inter- and intra-day expressed as relative standard deviation were 2.73∼8.79 %. No significant difference was found based on ANOVA; 90% confidance intervals (91.77∼101.94% for AUC0-t; 90.44∼ 106.27% for AUC0-infinity; 92.22∼108.57% for Cmax) for the test and reference drugs were found within FDA guideline of 80∼125%. Based on these statistical considerations, it was concluded that test drug was bioequivalent to the reference drug and therefore, may be interchangeably in the management of allergic or bronchial asthma and prophylaxis of mucositis due to cancer chemoradiotherapy. This validated method was found to be good performance on PK and BE studies for AZ. (Cancer Prev Res 12, 84-91, 2007). 

Author (s)  Details

Professor Ju-Seop Kang,
Department of Pharmacology and Clinical Pharmacology Laboratory, College of Medicine, Hanyang University, Seoul 133-791, Korea.

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