Development of acetazolamide loaded bilosomes for improved ocular delivery: Preparation, characterization and in vivo evaluation

Niosomes have been reported as a possible approach to improve the low corneal penetration and bioavailability characteristics shown by conventional ophthalmic vehicles. Niosomes formed from Span 40 or Span 60 and cholesterol in the molar ratios of 7:4, 7:6 and 7:7 were prepared using reverse-phase evaporation and thin film hydration methods. The prepared systems were characterized for entrapment efficiency, size, shape and in vitro drug release. Stability studies were carried out to investigate the leaching of drug from niosomes during storage. The intraocular pressure (IOP) lowering activity of acetazolamide niosomal formulations in rabbits was measured using ShiØtz tonometer. Histological examination for the corneal tissues of rabbits receiving niosomal formulations was carried out for assessment of the ocular irritancy of niosomes. The results showed that the type of surfactant, cholesterol content and the method of preparation altered the entrapment efficiency and drug release rate from niosomes. Higher entrapment efficiency was obtained with multilamellar niosomes prepared from Span 60 and cholesterol in a 7:6 molar ratio. Niosomal formulations have shown a fairly high retention of acetazolamide inside the vesicles (approximately 75%) at a refrigerated temperature up to a period of 3 months. Each of the tested acetazolamide niosomes prepared by either method produced a significant decrease in IOP compared to the solution of free drug and plain niosomes. Multilamellar acetazolamide niosomes formulated with Span 60 and cholesterol in a 7:4 molar ratio were found to be the most effective and showed prolonged decrease in IOP. Histological examination of corneal tissues after instillation of niosomal formulation for 40 days showed slight irritation in the substantia propria of the eye which is reversible and no major changes in tissues were observed.

The objective of the present research was to investigate the feasibility of using non-ionic surfactant vesicles (niosomes) as carriers for the ophthalmic controlled delivery of a water soluble local antibiotic; gentamicin sulphate. Niosomal formulations were prepared using various surfactants (Tween 60, Tween 80 or Brij 35), in the presence of cholesterol and a negative charge inducer dicetyl phosphate (DCP) in different molar ratios and by employing a thin film hydration technique. The ability of these vesicles to entrap the studied drug was evaluated by determining the entrapment efficiency %EE after centrifugation and separation of the formed vesicles. Photomicroscopy and transmission electron microscopy as well as particle size analysis were used to study the formation, morphology and size of the drug loaded niosomes. Results showed a substantial change in the release rate and an alteration in the %EE of gentamicin sulphate from niosomal formulations upon varying type of surfactant, cholesterol content and presence or absence of DCP. In-vitro drug release results confirmed that niosomal formulations have exhibited a high retention of gentamicin sulphate inside the vesicles such that their in vitro release was slower compared to the drug solution. A preparation with 1:1:0.1 molar ratio of Tween 60, cholesterol and DCP gave the most advantageous entrapment (92.02% +/- 1.43) and release results (Q(8h) = 66.29% +/- 1.33) as compared to other compositions. Ocular irritancy test performed on albino rabbits, showed no sign of irritation for all tested niosomal formulations.