Nepafenac-Loaded Cyclodextrin/Polymer Nanoaggregates: A New Approach to Eye Drop Formulation

Area of Science:

• Ophthalmic drug delivery
• Polymer chemistry
• Materials science

Background:

• Topical ocular drug administration faces challenges in drug bioavailability.
• Cyclodextrin (CD)/drug complexes can self-assemble into aggregates to improve drug delivery.
• Novel formulation strategies are needed to enhance the efficacy of eye drops.

Purpose of the Study:

• To design a novel eye drop formulation utilizing cyclodextrin/drug nanoaggregates.
• To investigate the physicochemical properties of aggregates formed by various CDs and polymers.
• To optimize formulations for enhanced topical delivery of nepafenac.

Main Methods:

• Complex formation analyzed using differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR), and ¹H nuclear magnetic resonance spectroscopy (¹H-NMR).
• Physicochemical properties of aggregates, including size and viscosity, were evaluated.
• Formulation optimization using a mixture of gamma-cyclodextrin (γCD) and hydroxypropyl-β-cyclodextrin (HPβCD).

Main Results:

• HPβCD demonstrated superior solubilization capabilities, while γCD excelled in promoting nanoaggregate formation.
• Inclusion complex formation was confirmed through DSC, FT-IR, and ¹H-NMR analyses.
• Optimal formulation achieved with a 15% (w/v) γCD and 8% (w/v) HPβCD mixture, yielding aggregates <1 µm and viscosity ~10⁻¹⁹ cP.

Conclusions:

• Formulations incorporating polymeric drug/CD nanoaggregates offer a viable strategy for enhanced topical ocular delivery.
• The developed nanoaggregate formulations show potential for improving the bioavailability of nepafenac.
• Mixtures of CDs can be effectively used to prepare nanoaggregate formulations with desirable physicochemical properties for eye drops.