Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 290, Issue 1-2, Pages 155-159Publisher
ELSEVIER
DOI: 10.1016/j.ijpharm.2004.10.026
Keywords
timolol maleate; niosomes; bioadhesion; glaucoma; intraocular pressure; corneal permeability
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In the present study chitosan (REVTMbio1) or Carbopol (REVTMbio2 and 3) coated niosomal timolol maleate (0.25%) formulations were prepared by reverse phase evaporation (REV) and compared to timolol solution (TMS; 0.25%) in terms of in vitro release and IOP lowering pharmacodynamic effect. The in vitro release phase of timolol (91% release in 2 h) was extended significantly by its incorporation into niosomes and further by the polymer coating (40-43% release upto 10 h). The developed formulations were evaluated for their pharmacodynamics in albino rabbits, by measuring intraocular pressure (IOP) using a non-contact pneumatonometer, and were compared to a marketed in situ gel forming solution of timolol (Timolet GFS, 0.5%; Sun Pharma). REVTMbio1 formulation showed a more sustained effect of upto 8 h (vis a vis 6 h for carbopol-coated niosomes). TMS in comparison showed effect for only 2 It though the peak effect was slightly more (14%). Lowering of IOP in the contralateral eye (20-40% as compared to 100% in case of TMS), considerably reduces with REV and REVbio formulations indicating lesser systemic side effects. Moreover, the results of REVTMbio1 formulation containing 0.25% of timolol maleate compared well with the 0.5% marketed get formulation, indicating our formulation to be significantly better considering that similar effect is obtained at half the concentration. The later becomes especially important in context to the cardiovascular side effects associated with ocular timolol maleate therapy. (C) 2004 Elsevier B.V. All rights reserved.
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