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Antihypertensive activity and molecular interactions of irbesartan in complex with 2‐hydroxypropyl‐β‐cyclodextrin
- Source :
- Chemical Biology & Drug Design. 96:668-683
- Publication Year :
- 2020
- Publisher :
- Wiley, 2020.
-
Abstract
- Irbesartan (IRB) exerts beneficial effects either alone or in combination with other drugs on numerous diseases, such as cancer, diabetes, and hypertension. However, due to its high lipophilicity, IRB does not possess the optimum pharmacological efficiency. To circumvent this problem, a drug delivery system with 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD) was explored. The 1:1 complex between IRB and 2-HP-β-CD was identified through ESI QTF HRMS. Dissolution studies showed a higher dissolution rate of the lyophilized IRB-2-HP-β-CD complex than the tablet containing IRB at pH = 1.2. DSC results revealed the differences of the thermal properties between the complex and various mixtures consisting of the two components, namely IRB and 2-HP-β-CD. Interestingly, depending on the way the mixture preparation was conducted, different association between the two components was observed. Molecular dynamics (MD) simulations predicted the favorable formation of the above complex and identified the dominant interactions between IRB and 2-HP-β-CD. In vitro pharmacological results verified that the inclusion complex not only preserves the binding affinity of IRB for AT1R receptor, but also it slightly increases it. As the complex formulation lacks the problems of the tablet, our approach is a promising new way to improve the efficiency of IRB.
- Subjects :
- Spectrometry, Mass, Electrospray Ionization
Drug Compounding
Molecular Conformation
Molecular Dynamics Simulation
01 natural sciences
Biochemistry
Irbesartan
2 hydroxypropyl β cyclodextrin
Drug Discovery
medicine
Humans
Beneficial effects
Antihypertensive Agents
Pharmacology
Molecular interactions
010405 organic chemistry
Chemistry
Organic Chemistry
Combinatorial chemistry
2-Hydroxypropyl-beta-cyclodextrin
0104 chemical sciences
Drug Liberation
010404 medicinal & biomolecular chemistry
Freeze Drying
Solubility
Drug delivery
Lipophilicity
Molecular Medicine
medicine.drug
Subjects
Details
- ISSN :
- 17470285 and 17470277
- Volume :
- 96
- Database :
- OpenAIRE
- Journal :
- Chemical Biology & Drug Design
- Accession number :
- edsair.doi.dedup.....1056b9b60da28e5e32bbb7e21dfe0567