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

• Published in: Journal of pharmaceutical investigation Vol. 50; no. 1; pp. 59 - 70
• Main Authors: Ramadan, Afaf A., Eladawy, Shereen A., El-Enin, Amal Saber Mohammed Abu, Hussein, Zeinab M.
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 2020; 한국약제학회
• Subjects: Biomedical and Life Sciences; Biomedicine; Original Article; 약학; Draize test; Entrapment efficiency; Timolol maleate; IOP measurement; Ocular gel; Niosomes
• ISSN: 2093-5552; 2093-6214
• DOI: 10.1007/s40005-019-00427-1

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.