No abstract

Lowering Intraocular pressure (IOP) is a main therapeutic objective in glaucoma patients because IOP is an important risk factor for glaucoma progression. The objective of this work was to formulate and evaluate, in vitro and in vivo, a stable and effective Solid in Oil (S/O) topical formulation of the antiglaucoma drug, timolol maleate (TM). S/O dispersions were prepared by emulsification of aqueous TM solutions in cyclohexane using different amount of the span 85 then lyophilizing the emulsion to produce TM – Span 85 complexes. The complexes were then dispersed in castor oil using tip sonicator to produce S/O nanodispersions. S/O nanodispersions were evaluated in terms of particle size, polydispersity index, encapsulation efficiency, morphology, physical stability, as well as transcorneal permeation and accumulation of TM. In addition, the in vivo tolerability and efficacy of the prepared formulation in lowering intraocular pressure were evaluated in rabbits. Spherical nanoparticles of TM with a particle size of about 134-155 nm were successfully prepared and found to be physically stable. The encapsulation efficiency was high and was found to be dependent on the level of Span 85 used. In comparison to TM solution, S/O nanodispersion enhanced TM permeation and decreased accumulation in transcorneal diffusion studies. In addition, application TM S/O nanodispersion onto rabbit eyes resulted in a significant reduction in IOP in comparison to TM aqueous solution.

In this study we evaluated the effect of Na Lauryl sulfate (SLS) on the water-uptake and release properties of Na Tripolyphosphate (TPP)-cross linked chitosan beads. Chitosan beads were prepared by dropping riboflavin-loaded, chitosan (CS) solution into a curing medium composed of either an aqueous solution of TPP, SLS or a combination of these solutes. The resultant beads were characterized in terms of their size, drug encapsulation efficiency, water uptake properties by gravimetry and image analysis. Drug release properties of the prepared beads were studied using USP Apparatus 1 in media with different pH and ionic strength. Composites (CS/TPP, CS/SLS, and CS/TPP/SLS) were also evaluated using DSC, FTIR and contact angle measurements. Encapsulation efficiency was found to be 93%, 93.2% and 93.1% for CS/TPP, CS/SLS, and CS/TPP/SLS beads respectively and did not show any dependence on the composition of the curing medium for riboflavin. FTIR data suggested the presence of electrostatic interactions between positively charged amine group of CS and the negatively charged TPP and SLS. Drug release from the prepared beads was prolonged with CS/SLS beads releasing the drug faster than CS/TPP beads. The slowest drug release was observed in the case of CS/TPP/SLS beads. Drug release from the different types of beads was pH-dependent with the fastest release observed in 0.1 N HCl. Gravimetric water uptake was highest for CS/SLS beads followed by CS/TPP and CS/TPP/SLS respectively. Swelling study using image analysis showed a similar trend to the gravimetric water uptake results. The drug release and water uptake results could be explained by the effect of SLS on the wettability of the beads and the ability of the release medium to hydrate them which was confirmed by the high contact angle between water and CS/TPP/SLS composites.