Losartan Interactions with 2-Hydroxypropyl-β-CD.

Area of Science:

• Pharmaceutical Sciences
• Physical Chemistry
• Materials Science

Background:

• Losartan potassium salt (LSR) is a widely used antihypertensive medication.
• Formulating LSR with 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD) may enhance its pharmacological activity.
• Understanding the molecular interactions is crucial for optimizing drug delivery and efficacy.

Purpose of the Study:

• To investigate the molecular interactions between losartan potassium salt and 2-hydroxypropyl-β-cyclodextrin.
• To confirm the complexation and evaluate its properties using various analytical techniques.
• To provide evidence for the potential of this new formulation in pharmaceutical applications.

Main Methods:

• Differential Scanning Calorimetry (DSC) to analyze thermal properties and complexation.
• Nuclear Magnetic Resonance (NMR) spectroscopy (chemical shift and T1 values) to confirm complexation.
• Molecular Dynamics (MD) simulations to study the reversibility and nature of the complexation.

Main Results:

• DSC indicated distinct thermal properties for the lyophilized LSR/2-HP-β-CD complex compared to a simple mixture.
• NMR studies confirmed complexation through observed chemical shift changes and altered T1 values.
• MD calculations demonstrated a reversible and favorable complexation between LSR and 2-HP-β-CD.

Conclusions:

• The study provides strong evidence of molecular complexation between losartan potassium salt and 2-hydroxypropyl-β-cyclodextrin.
• The observed favorable and reversible complexation suggests potential for improved pharmacological profiles.
• This LSR/2-HP-β-CD formulation warrants further investigation through biological experiments for its antihypertensive potential.