The Chemical Stability Characterization and Kinetics of Statins in Aqueous Cyclodextrin Ocular Preparations: A...

Area of Science:

• Pharmaceutical Sciences
• Ophthalmology
• Drug Delivery

Background:

• Topical statin therapy shows potential for ocular diseases like age-related macular degeneration.
• Effective delivery to the posterior eye segment is hindered by poor aqueous solubility, chemical instability, and ocular barriers.
• Cyclodextrins (CDs) can enhance solubility and stability, but their effect on the lactone/hydroxyacid equilibrium in eye drops is unknown.

Purpose of the Study:

• To investigate the impact of cyclodextrin (CD) concentration and type on the lactone/hydroxyacid equilibrium of simvastatin and atorvastatin.
• To define formulation parameters, including statin form, CD type and concentration, and pH, for stable eye drop development.

Main Methods:

• Simvastatin or atorvastatin was incubated in buffered solutions (pH 2.0-9.5) with various cyclodextrins (RMβCD, HPβCD, γ-CD, SBEβCD) at 0%, 5%, and 10% concentrations.
• UPLC was used to quantify lactone and hydroxyacid forms over time, and rate constants were calculated.
• Phase solubility studies were performed to characterize equilibrium behavior.

Main Results:

• The lactone form of statins was most stable at pH 4.5; the hydroxyacid form predominated at pH ≥ 7.
• γ-CD and HPβCD accelerated lactone hydrolysis, while RMβCD demonstrated a stabilizing effect.
• Increasing CD concentration from 5% to 10% offered minimal additional stabilization.

Conclusions:

• Precise pH control is critical for developing chemically stable statin eye drops.
• The choice of cyclodextrin significantly influences statin stability, with RMβCD being a promising option.
• Selecting the appropriate statin form is essential for successful eye drop formulation.