Ophthalmic, emulsions optimization

The efficacy, safety, tolerability, and optimal dose of ciclosporin eye-drops have been studied in a randomized, double-masked, vehicle-controlled multicenter trial in 162 patients with keratoconjunctivitis sicca with or without Sjogren s disease and refractory to conventional treatment (48). Ciclosporin ophthalmic emulsion 0.05, 0.1, 0.2, or 0.4%, or the vehicle alone was instilled twice daily into both eyes for 12 weeks, followed by a 4-week observation period. There was no clear dose-response relation ciclosporin 0.1% emulsion produced the most consistent improvement in objective and subjective endpoints and ciclosporin 0.05% gave the most consistent improvement in sjmptoms. The vehicle also performed well, perhaps because of its long residence time on the ocular surface. There were no significant adverse effects, no microbial overgrowth, and no residence time of the vehicle emulsion on the ocular surface. AH treatments were well tolerated and the highest ciclosporin blood concentration detected was 0.16 ng/ml. 

In conclusion, the approval of Restasis by the FDA is an important milestone in lipid emulsion research for ophthalmic application. This approval reflects the achievements of the last decade in terms of the availability of better ingredients, improved manufacturing processes, feasibility of sterilization, and better understanding of the optimization process. In all of the comparative studies done so far, positively charged SME achieved better ocular bioavailability regardless of the studied drug. Research efforts are underway to further explore the mechanism of interaction of positively charged SMEs with ocular tissues and to translate the results of this research into enhanced clinical performance. 

For instance, Yadav and Ahuja prepared nanoparticles using gum cordia as the polymer and to evaluate them for ophthalmic delivery of fluconazole. A w/o/w emulsion containing fluconazole and gum cordia in aqueous phase, methylene chloride as the oily phase, and dioctyl sodium sulfosuccinate and polyvinyl alcohol as the primary and secondary emulsifiers, respectively, were cross-linked by the ionic gelation technique to produce a fluconazole-loaded nanoreservoir system. The formulation of nanoparticles was optimized using response surface methodology. Multiple response simultaneous optimizations using the desirability approach were used to find optimal experimental conditions. The optimal conditions were found to be concentrations of gum cordia (0.85%, w/v), di-octyl sodium sulfosuccinate (9.07%, w/v), and fluconazole (6.06%, w/v). On comparison of the optimized nanosuspension formulation with commercial formulation, it was found to provide comparable in vitro corneal permeability of... 

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