Study of the Acidic, Basic, and Thermal Degradation Kinetics of Three Antihypertensive Drugs—Individually and in Combination
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 anothe...
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| author | Nebojša Mandić-Kovacević Irena Kasagić-Vujanović Biljana Gatarić Ranko Škrbić Ana Popović Bijelić |
| author_facet | Nebojša Mandić-Kovacević Irena Kasagić-Vujanović Biljana Gatarić Ranko Škrbić Ana Popović Bijelić |
| author_sort | Nebojša Mandić-Kovacević |
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| description | 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. |
| format | Article |
| id | doaj-art-56602eb66c854e4ca32a711d13db9c86 |
| institution | Kabale University |
| issn | 1999-4923 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
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| series | Pharmaceutics |
| spelling | doaj-art-56602eb66c854e4ca32a711d13db9c862024-11-26T18:17:51ZengMDPI AGPharmaceutics1999-49232024-11-011611141010.3390/pharmaceutics16111410Study of the Acidic, Basic, and Thermal Degradation Kinetics of Three Antihypertensive Drugs—Individually and in CombinationNebojša Mandić-Kovacević0Irena Kasagić-Vujanović1Biljana Gatarić2Ranko Škrbić3Ana Popović Bijelić4Department of Pharmacy, Faculty of Medicine, University of Banja Luka, Save Mrkalja 14, 78000 Banja Luka, The Republic of Srpska, Bosnia and HerzegovinaDepartment of Drug Analysis, Faculty of Medicine, University of Banja Luka, Save Mrkalja 14, 78000 Banja Luka, The Republic of Srpska, Bosnia and HerzegovinaDepartment of Pharmaceutical Technology and Cosmetology, Faculty of Medicine, University of Banja Luka, Save Mrkalja 14, 78000 Banja Luka, The Republic of Srpska, Bosnia and HerzegovinaCentre for Biomedical Research, Faculty of Medicine, University of Banja Luka, Save Mrkalja 14, 78000 Banja Luka, The Republic of Srpska, Bosnia and HerzegovinaFaculty of Physical Chemistry, University of Belgrade, Studentski Trg 12–16, 11158 Belgrade, SerbiaBackground/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.https://www.mdpi.com/1999-4923/16/11/1410perindopril tert-butylamineamlodipine besylateindapamidestabilitykineticsfixed drug combinations |
| spellingShingle | Nebojša Mandić-Kovacević Irena Kasagić-Vujanović Biljana Gatarić Ranko Škrbić Ana Popović Bijelić Study of the Acidic, Basic, and Thermal Degradation Kinetics of Three Antihypertensive Drugs—Individually and in Combination Pharmaceutics perindopril tert-butylamine amlodipine besylate indapamide stability kinetics fixed drug combinations |
| title | Study of the Acidic, Basic, and Thermal Degradation Kinetics of Three Antihypertensive Drugs—Individually and in Combination |
| title_full | Study of the Acidic, Basic, and Thermal Degradation Kinetics of Three Antihypertensive Drugs—Individually and in Combination |
| title_fullStr | Study of the Acidic, Basic, and Thermal Degradation Kinetics of Three Antihypertensive Drugs—Individually and in Combination |
| title_full_unstemmed | Study of the Acidic, Basic, and Thermal Degradation Kinetics of Three Antihypertensive Drugs—Individually and in Combination |
| title_short | Study of the Acidic, Basic, and Thermal Degradation Kinetics of Three Antihypertensive Drugs—Individually and in Combination |
| title_sort | study of the acidic basic and thermal degradation kinetics of three antihypertensive drugs individually and in combination |
| topic | perindopril tert-butylamine amlodipine besylate indapamide stability kinetics fixed drug combinations |
| url | https://www.mdpi.com/1999-4923/16/11/1410 |
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