Study of the Acidic, Basic, and Thermal Degradation Kinetics of Three Antihypertensive Drugs-Individually and in
Nebojša Mandić-Kovacević1,2, Irena Kasagić-Vujanović3, Biljana Gatarić4
1Department of Pharmacy, Faculty of Medicine, University of Banja Luka, Save Mrkalja 14, 78000 Banja Luka, The Republic of Srpska, Bosnia and Herzegovina.
Background/Objectives:
The importance of fixed-dose combinations (FDCs) for the treatment of hypertension is well established. However, from a stability perspective, FDCs present a challenge since the degradation of one active pharmaceutical ingredient (API) can be affected by the presence of another API. The aim of this study was to compare the degradation behaviors and evaluate the degradation kinetics of three antihypertensive drugs, perindopril tert-butylamine (PER), amlodipine besylate (AML), and indapamide (IND).
Methods:
The degradation processes were studied using the previously developed reverse phase high-performance liquid chromatographic (RP-HPLC) method after exposing each drug individually, as well as the combinations of two/three drugs, to different stress factors, such as light, oxidation, acidic, basic, or neutral pH values at different temperatures.
Results:
The results show that PER is most unstable under basic conditions and that AML displays a negative, while IND displays a positive effect, on PER stability when combined. AML is most affected by basic conditions and oxidation, and its stability is affected by both drugs positively; IND undergoes extreme photolysis, which is positively affected by AML but negatively by PER.
Conclusions:
Great care must be taken when formulating FDCs with these three drugs, as well as solutions or oral suspensions adjusted for geriatric or pediatric populations, since the stability of all three drugs is greatly affected by pH conditions, as well as light or oxidation factors and their interactions.
Related Concept Videos
01:14Time Course of Drug Effect
01:23Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance
A study on guinea pigs examined the...
00:59Model-Independent Approaches for Pharmacokinetic Data: Noncompartmental Analysis
One important characteristic of noncompartmental analyses is that drug exposure increases proportionally with increasing doses. This...
01:25Drug Distribution as One-Compartment Model and Elimination by Nonlinear Pharmacokinetics: Overview
For instance, consider the metabolism of sodium salicylate. This compound is metabolized into two distinct substances: a glucuronide and a glycine conjugate. The rate of conjugation depends...
01:17Kinetics of Drug Elimination
Drug clearance depends on the rate of drug elimination and its plasma concentration. Another important parameter is the half-life of a drug, which is the time required for its concentration to decrease by half. In most cases, drug clearance follows first-order...
01:30Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors