A novel liposomal formulation for ocular delivery of caspofungin: an experimental study by quality by design-based approach

Aim: This study focuses on the development of a Caspofungin liposome for efficient ocular delivery by enhancing corneal penetration.
Method: Quality by design (QbD) approach was adopted to identify critical factors that influence final liposomal formulation. The liposome developed using thin film hydration after optimization was subjected to characterization for physicochemical properties, irritation potential and corneal uptake.
Results: The numerical optimization suggests an optimal formulation with a desirability value of 0.706, using CQAs as optimization goals with 95% prediction intervals. The optimized formulation showed no signs of irritation potential along with observation of significant corneal permeation.
Conclusion: The liposomal formulation increased the permeability of Caspofungin, which could enhance the efficacy for the treatment of conditions, like fungal keratitis.
Screening of optimal combination of excipients: The selection of lipid, Csp:lipid, and lipid-CH was performed using solubility analysis and sedimentation behavior.
QbD approach: Systematic development of Caspofungin containing liposomes was conducted by using QbD approach.
Optimization of formulation: Design space was generated, verified and optimization was carried out using Box-Behnken design.
Characterization of optimized formulation: Physico-chemical characterization conducted for the parameters, such as, particle size, PDI, zeta potential, osmolarity, TEM analysis, SEM analysis, etc. showed effective preparation of liposomes.
In vitro release study: Optimized liposomes showed sustained release behavior of Csp with more than 90% of the Csp is released within 12 h.
Ocular irritation study: Optimized formulation showed no signs of eye irritation potential with irritation score of 0.3.
Corneal permeation study: Effective corneal permeation was observed from ex vivo transcorneal permeation and CLSM study.
Stabillity study: The optimized formulation showed no significant alterations in the physico-chemical properties for the 6-month study period.