Binary polymeric blends to microencapsulate nitroflurbiprofen: physicochemical and in silico studies.

Area of Science:

• Materials Science
• Pharmaceutical Sciences
• Computational Chemistry

Background:

• Nitroflurbiprofen (NFP) is a practically insoluble liquid drug, posing challenges for effective drug delivery.
• Microencapsulation in hydrophilic polymers offers a potential strategy to improve the solubility and release of poorly soluble drugs.
• Understanding polymer miscibility and drug-polymer interactions is crucial for designing stable and effective drug delivery systems.

Purpose of the Study:

• To microencapsulate Nitroflurbiprofen (NFP) in poly(N-vinylpyrrolidone) (PVP), polyaminomethacrylate (PAMA), and their binary blends.
• To assess the miscibility of PAMA/PVP blends and their impact on NFP release and apparent solubility.
• To investigate the role of molecular dynamics (MD) simulations in predicting drug-polymer interactions and stabilizing supersaturated systems.

Main Methods:

• Microencapsulation of NFP using PVP, PAMA, and PAMA/PVP blends.
• Solid-state (DSC, ATF-FTIR) and solution (viscometry) characterization of polymer miscibility.
• In vitro NFP release studies under supersaturation conditions.
• In silico molecular dynamic (MD) simulations and docking analyses of drug/polymer/water interactions.

Main Results:

• PAMA and PVP were found to be miscible only in aqueous solutions.
• NFP release exhibited a non-monotonic pattern, forming unstable supersaturated systems with drug separation.
• PVP/PAMA micromatrices significantly reduced the instability of supersaturated NFP solutions, achieving a supersaturation degree (SD) of at least 3 after 5 minutes.
• MD simulations highlighted the crucial role of water molecules and hydrogen bonding in PAMA/PVP compatibilization and NFP supersaturation stabilization.

Conclusions:

• Hydrophilic micromatrices composed of PAMA/PVP blends can enhance the apparent solubility of Nitroflurbiprofen (NFP).
• The use of PAMA/PVP blends effectively stabilizes supersaturated NFP solutions, mitigating drug precipitation.
• Molecular dynamic simulations provide valuable insights into polymer miscibility, drug-polymer interactions, and the stabilization mechanisms in supersaturated drug delivery systems.