Tag Archives: Indapamide

Food-effect study on the pharmacokinetics of indapamide prolonged-release tablets

Maria Codreanu1,2, Diana Iacob3, Maria Ioana Onofrei4,5, Ana-Maria Vlase6, Dana Maria Muntean1, Laurian Vlase1

1. Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy, University of Medicine and Pharmacy “Iuliu Haţieganu”, Cluj-Napoca, Romania
2. Regulatory Affairs Department, Antibiotice SA, Iași, Romania
3. Center for Drug Evaluation, Antibiotice SA, Iași, Romania
4. Clinic of Infectious Diseases, “Sf. Parascheva” Clinical Hospital of Infectious Diseases, Iasi, Romania
5. Department of Infectious Diseases, Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania
6. Department of Pharmaceutical Botany, Faculty of Pharmacy, University of Medicine and Pharmacy “Iuliu Haţieganu”, Cluj-Napoca, Romania

DOI: 10.2478/amma-2024-0032

Objective: A comparative study was performed to evaluate the food impact on the pharmacokinetics of indapamide 1.5 mg prolonged release tablets (SR).
Methods: The data evaluated were collected from 2 randomized, single dose, 2-way crossover bioequivalence studies with administration of indapamide to healthy Caucasian volunteers under fasting and fed conditions, respectively. Forty-four eligible subjects aged 19–39 years were enrolled in both studies: 22 subjects received indapamide under fasting (study 1) and the other 22 under fed (study 2) conditions. Blood samples were collected following the same schedule before and up to 96.0 hours after drug administration. Blood concentration of indapamide were quantified by a validated LC-MS/MS method. A non-compartmental analysis was used to calculate the pharmacokinetic parameters. Mathematical deconvolution was applied to assess indapamide absorption. Statistical significance for differences in key pharmacokinetic parameters was evaluated using an ANOVA test, with a significance threshold of p < 0.05.
Results: In total, 44 subjects were included in analysis. The outcomes demonstrated that ingestion of food independently reduced the mean of tmax by 4.64 h and increased the value of Cmax by 19.7 ng/mL, while the AUC remained unchanged.
Conclusions: Notably, differences in drug absorption rate obtained after co-administration of indapamide with food had no significant influence in safety and efficacy of the drug.

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Development of a Dissolution Method for Modified Release Tablets Containing an Insoluble Active Substance

Kelemen Éva Katalin1, Kelemen LJ1, Gyéresi Á2, Imre Silvia3, Obreja Mona1

1 Gedeon Richter Romania S.A., Tîrgu Mureș, Romania
2 Department of Pharmaceutical Chemistry, University of Medicine and Pharmacy, Tîrgu Mureș, Romania
3 Department of Analytical Chemistry and Drug Control, University of Medicine and Pharmacy, Tîrgu Mureș, Romania

Objective: The aim of the present work is to develop a discriminative dissolution method for a practically insoluble pharmaceutical active substance such as indapamide.
Methods: Dissolution testing was performed in compliance with USP, using USP apparatus 2. The proper dissolution medium and the optimal rotation per minutes of the apparatus were optimized. In order to quantify the dissolution of indapamide from modified release tablets, a high liquid chromatographic method was developed and validated.
Results: An HPLC method was developed in order to provide adequate specificity trying several column types and different mobile phases. We selected the proper dissolution medium based on indapamide solubility, we determined the optimal speed of rotation of the dissolution tester for the indapamide in the selected medium, then we proved the discriminating power of the developed dissolution method.
Conclusions: A robust and discriminating HPLC method for analyzing dissolution samples containing indapamide was developed and successfully validated.

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Screening the Dissolution Performance of the Modified Release Tablets Containing Insoluble Active Substance in Different Dissolution Media

Kelemen Éva Katalin1, Obreja Mona1, Gyéresi Árpád2

1 SC Gedeon Richter Romania SA, Tîrgu Mureș, Romania
2 Department of Pharmaceutical Chemistry, University of Medicine and Pharmacy, Tîrgu Mureș, Romania

Objective: The aim of the present work was to examine a test and a marketed product containing indapamide in different dissolution media: hydrochloric acid, acetate buffer solution, phosphate buffer solution, fasted state simulated intestinal fluid and fed state simulated intestinal fluid.
Methods: Dissolution testing was performed in compliance with USP, using USP apparatus 2. In order to quantify the dissolution of indapamide from modified release tablets, a high liquid chromatographic method was developed.
Results: The dissolution profiles registered in different dissolution media were represented graphically and we calculated the difference factor f1 and the similarity factor f2 between the test and the marketed product’s dissolution profiles obtained in different dissolution media. It can be observed that the dissolution behavior of the test and the marketed product is very similar in hydrochloric acid, phosphate buffer solution, in fasted state simulated intestinal fluid and fed state simulated intestinal fluid, but it is not similar in acetate buffer solution.
Conclusions: In case of poorly soluble active substances, such us indapamide, it is very difficult to develop a dissolution method in order to predict the in vivo behavior. It is necessary to investigate the dissolution profiles not only in the routine dissolution medium, and in three different pH solutions, but in biorelevant media, too.

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Analytical Performance of an HPLC and CZE Methods for the Analysis and Separation of Perindopril Erbumine and Indapamide

Ion Valentin*, Imre Silvia, Cârje Anca Gabriela, Muntean Daniela Lucia

Department of Analytical Chemistry and Drug Analysis, Faculty of Pharmacy, University of Medicine and Pharmacy of Tîrgu Mureș, Romania

DOI: 10.1515/amma-2015-0073

Introduction: Perindopril, as an angiotensin converting enzyme inhibitor and indapamide, as a thiazide like diuretic, can be administrated together for the treatment of high blood preasure and other cardiovascular diseases. The aim of this study was to develop two simple and reliable separation methods for perindopril and indapamide by high performance liquid chromatography and capillary zone electrophoresis in order to evaluate their behaviour under separation conditions, for simultaneous separation.
Materials and methods: Standard solutions of perindopril erbumine and indapamide in proper solvents were analized. An Agilent 1100 series HPLC system was used for the separation of the two analytes on a C18 stationary phase (Zorbax Stable Bond 3.5 µm), under an isocratic elution. As a comparative method, an Agilent 7100 series capillary electrophoresis system was used for the development of the electrophoretic method.
Results: Both developed methods turned to comply to the separation performance parameters such as resolution and selectivity, with low limits of detection, wide range of liniarity. No statistical difference concerning precision of the qualitative parameters was observed. Time analysis less than 5 minutes both for chromatographic and electrophoretic separations proved to generate cost and time effective analysis methods.
Conclusions: Two analytical methods, HPLC and CZE respectively, for the separation of perindoprile erbumine and indapamide have been successfully developed, both recording satisfactory analytical parameters.

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