Study of the Acidic, Basic, and Thermal Degradation Kinetics of Three Antihypertensive Drugs-Individually and in Combination

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...

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Published in:Pharmaceutics 2024-11, Vol.16 (11), p.1410
Main Authors: Mandić-Kovacević, Nebojša, Kasagić-Vujanović, Irena, Gatarić, Biljana, Škrbić, Ranko, Popović Bijelić, Ana
Format: Article
Language:English
Subjects:
Amlodipine
amlodipine besylate
Antihypertensives
Blood pressure
Caustic soda
Drug development
Drug therapy
Drug therapy, Combination
Drugs
fixed drug combinations
High performance liquid chromatography
Hydrochloric acid
Hydrogen peroxide
Hypertension
Indapamide
Kinetics
Oxidation
perindopril tert-butylamine
Pharmaceutical industry
Potassium
stability
Temperature
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Summary: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). 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. 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. 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.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics16111410