Development and investigation of timolol maleate niosomal formulations for the treatment of glaucoma

  • Afaf A. Ramadan
  • Shereen A. Eladawy
  • Amal Saber Mohammed Abu El-EninEmail author
  • Zeinab M. Hussein
Original Article


The objective of the present study was to develop niosomal gels loaded with Timolol Maleate (TM), Non-selective beta-adrenergic receptor antagonist, for prolonged duration and improved bioavailability for glaucoma treatment. TM niosomes were prepared by film hydration method with various mixtures of different non-ionic surfactants including Span 20, 40, 60 and Tween 20, 40, along with cholesterol. The prepared vesicles were evaluated for entrapment efficiency, in vitro drug release, particle size, zeta potential and morphology by optical and transmission electron microscopy (TEM). The selected formulations were incorporated into Sodium carboxymethyl cellulose (CMC Na) and Carbopol 934 gels. Gel formulations were characterized for in vitro drug permeation and ex vivo drug permeation through bovine cornea. In addition, stability study, isotonicity test and in-vivo evaluation of the selected formulations were done. The results showed that, the niosomes formed were white and spherical in shape with uniform particle size. Formulations containing span 60 and that containing mixture of span 60 and tween 40 gave the highest entrapment efficiency (94.6% and 98.8%, respectively) and a sustained release of timolol maleate from the niosomes within 24 h (96% and 97.10%, respectively). The in vitro and ex vivo drug release studies showed that there was a slow and prolonged release of drug from niosomal gel formulations. Considering the in-vitro release, niosomal gel formulae GN5 and GN6 (containing CMC Na 3% w/w) were the best among the studied formulations. Draize test was carried out and the intra-ocular pressure lowering activity of prepared formulations were detected and compared with marketed Timogel. Formula containing 3% CMC Na showed relative bioavailability 1.6 times more than bioavailability of marketed Timogel.


Timolol maleate Niosomes Ocular gel Entrapment efficiency Draize test IOP measurement 



The authors are thankful to EIPICO (Egypt) for generous donation of timolol maleate and grateful to Egyptian Petroleum Research Institute for the DSC work and Research Institute of Ophthalmology for help in the in vivo work.

Compliance with ethical standards

Conflict of interest

The authors report no conflicts of interest in this work. Only the authors are responsible for the content and writing of this paper.


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Copyright information

© The Korean Society of Pharmaceutical Sciences and Technology 2019

Authors and Affiliations

  • Afaf A. Ramadan
    • 1
  • Shereen A. Eladawy
    • 1
  • Amal Saber Mohammed Abu El-Enin
    • 1
    Email author
  • Zeinab M. Hussein
    • 1
  1. 1.Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy (Girls)Al-Azhar UniversityCairoEgypt

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