Optimization of Difluprednate-Loaded Liposomes Using a Quality by Design (QbD) Approach

Şen E., Sağıroğlu A. A., Erginer Y.

22nd International Pharmaceutical Technology Symposium IPTS 2026, Ankara, Türkiye, 9 - 11 Eylül 2026, ss.1-3, (Özet Bildiri)

  • Yayın Türü: Bildiri / Özet Bildiri
  • Basıldığı Şehir: Ankara
  • Basıldığı Ülke: Türkiye
  • Sayfa Sayıları: ss.1-3
  • İstanbul Üniversitesi-Cerrahpaşa Adresli: Evet

Özet

Introduction: Difluprednate (DFP) is a synthetic glucocorticoid used for the treatment of postoperative inflammation and pain associated with endogenous uveitis (Prajapati & Loftsson, 2022). However, its poor aqueous solubility, the anatomical and physiological barriers of the eye limited ocular bioavailability (Sathe et al., 2025). Liposomes are promising vesicles for topical drug delivery to the eye (Moiseev et al., 2022). In this study, difluprednate-loaded liposomes were optimized using a Quality by Design (QbD) approach to improve their physicochemical properties.

Material-Methods: DFP was supplied by Abdi İbrahim Pharmaceuticals (Türkiye). The cholesterol and α-Phosphatidylcholine from soybean (SPC) were obtained from Sigma-Aldrich (Germany). Difluprednate-loaded liposomes were prepared using the thin-film hydration method with a rotary evaporator Buchi (Switzerland). Design optimization and statistical analyses were performed using Design-Expert software (version 13.0.5.0). The liposomal dispersion was extruded using a mini extruder (Avanti Polar Lipids, USA). Liposome particle size (PS), polydispersity index (PDI) and zeta potential analyses were performed using Malvern Zetasizer Pro (England). Central composite design (CCD) was applied to investigate the influence of formulation variables on critical quality attributes, including PS, zeta potential, and encapsulation efficiency (EE).

Results: The PS of the optimized formulation was found to be 156±0.78 nm, with a PDI of 0.14±0.02, a zeta potential of -1.15±0.92, and an EE of 85.45%.

Discussion: Difluprednate is a highly lipophilic corticosteroid with poor aqueous solubility, which limits its ocular bioavailability. Liposomes are ideal carriers for such drugs as they incorporate lipophilic compounds into their lipid bilayer, enhancing drug dispersion in aqueous media and formulation stability. In this study, optimized difluprednate-loaded liposomes showed nanoscale particle size, narrow size distribution, and high encapsulation efficiency. These results indicate that this liposomal formulation is a promising ocular delivery system for difluprednate and merits further in-vitro and ex-vivo evaluation.

Conclusions: Difluprednate-loaded liposomes demonstrated suitable physicochemical properties for ocular administration. The optimized formulation exhibited nanoscale particle size, narrow size distribution, and high encapsulation efficiency, indicating the successful development of a stable liposomal carrier system for difluprednate. Considering the poor aqueous solubility of difluprednate, the developed liposomal formulation represents a promising approach for ocular drug delivery. Further in vitro and ex vivo studies will be conducted to evaluate its therapeutic performance and ocular delivery potential.