Full Factorial Design, Optimization, In vitro and Ex vivo Studies of Ocular Timolol-Loaded Microsponges

  • Radwa M. A. Abd-Elal
  • Ghada H. ElosailyEmail author
  • Shadeed Gad
  • El-Sayed Khafagy
  • Yasser Mostafa
Original Article



Timolol maleate (TMM) is a hydrophilic model drug. The aim of this study was to formulate TMM-loaded microsponges to sustain TMM release and improve its corneal permeability compared with TMM-aqueous solution.


The modified quasi-emulsion solvent diffusion technique (water/oil/oil) was used to prepare TMM-loaded microsponges. The impact of the polymer type (X1) and drug:polymer ratio (X2) were studied and optimized, using full factorial design. The production yield (PY) %, entrapment efficiency (EE) %, particles size (PS), and TMM released % after 6 h were selected as dependent variables. Depended on the desirability value by using the Design-Expert® software version 11, the optimized formulation was selected and subjected to further studies, such as scanning electron microscopy (SEM), porosity determination, powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), ex vivo permeation study, and corneal hydration level.


The optimized formulation composed of TMM: EC within the proportion 1:9 exhibited PY of 96.55 ± 4.01%; EE of 72.00 ± 6.08%; PS (d90) of 6283.33 ± 145.71 nm and released 42.12 ± 3.93% of TMM after 6 h. Particles appeared porous with spherical shape. Thermal analysis proved that the drug has been homogeneously dispersed in its amorphous state. The optimized formulation showed higher corneal permeability about 1.45-fold higher than TMM-aqueous solution in a period of 6 h.


The modified quasi-emulsion diffusion technique (water/oil/oil) is suitable for improving EE of hydrophilic drug (TMM) and the optimized TMM-loaded microsponge was succeeded to retard the release of TMM and improve its corneal permeability.


Microsponges Water/oil/oil Timolol Optimization In vitro release Ex vivo permeation study 


Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Pharmaceutics, Faculty of PharmacyModern University for Technology & InformationCairoEgypt
  2. 2.Department of Pharmaceutics and Industrial Pharmacy, Faculty of PharmacyAl-Azhar UniversityCairoEgypt
  3. 3.Department of Pharmaceutics and Industrial Pharmacy, Faculty of PharmacySuez Canal UniversityIsmailiaEgypt
  4. 4.Department of Pharmaceutics, College of PharmacyPrince Sattam Bin Abdulaziz UniversityAl-KharjSaudi Arabia
  5. 5.Department of Pharmacology and Toxicology, Faculty of PharmacySuez Canal UniversityIsmailiaEgypt

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