Excipient-assisted vinpocetine nanoparticles: experiments and molecular dynamic simulations

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Computational Chemistry

Background:

• Poorly soluble drugs often exhibit low bioavailability.
• Hydrophilic excipients can improve drug solubility and dissolution.
• Nanoparticle formulation is a strategy to enhance drug delivery.

Purpose of the Study:

• To prepare and characterize vinpocetine (VIN) nanoparticles using different hydrophilic excipients.
• To evaluate the impact of excipients on VIN nanoparticle size, dissolution, and stability.
• To investigate the molecular interactions between VIN and excipients using molecular dynamics (MD) simulations.

Main Methods:

• Reactive precipitation was used to prepare excipient-assisted VIN nanoparticles.
• Particle size analysis was performed to determine nanoparticle dimensions.
• In vitro dissolution studies compared nanoparticle formulations with physical mixtures and raw drug.
• Molecular dynamics (MD) simulations were employed to study drug-excipient interactions.

Main Results:

• Hydroxypropylmethylcellulose (HPMC) was identified as a suitable excipient, yielding VIN nanoparticles with a mean size of 130 nm.
• VIN/HPMC nanoparticles exhibited significantly faster dissolution rates than physical mixtures and raw VIN.
• VIN/HPMC nanoparticles demonstrated superior dissolution profiles compared to VIN/polyvinylpyrrolidone (PVP) and VIN/lactose (LAC) nanoparticles.
• MD simulations revealed Coulomb and Lennard-Jones interactions between VIN and excipients, with limited hydrogen bonding.

Conclusions:

• HPMC is an effective excipient for preparing stable VIN nanoparticles with enhanced dissolution.
• Stronger interactions, primarily Lennard-Jones, between VIN and HPMC contribute to smaller particle size and improved performance.
• Excipient selection and drug-excipient interactions are critical for optimizing nanoparticle-based drug delivery systems.