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Purpose: The aim of the present study was to develop and optimize sinomenine hydrochloride (SIN) in situ gel for uveitis treatment.
Methods: Carbopol 940 was used as the gelling agent in combination with hydroxypropyl methylcellulose (HPMC), which acts as a viscosity enhancer. The formulations were prepared using various concentrations of Carbopol 940 and HPMC. The prepared in situ gels were evaluated for gellation, drug release, ocular irritation, elimination time and pharmacokinetic studies. Furthermore, the effect of SIN on the development of experimental autoimmune anterior uveitis (EAAU) was assessed.
Results: The optimum concentration of Carbopol was 0.1% (w/v), and that for HPMC was 0.4% (w/v). Which showed a significant enhancement in gel strength in the physiological condition while free flowing at non-physiological condition. Optimum formula F(2-3) consisting of 0.5% SIN was prepared and kept as gel group, and 0.5% SIN solution was prepared and kept as control group. Gel group provided sustained release of the drug over a period of 480 min. No evidence of overt toxicity and irritation was observed in any study. The elimination time of control group and gel group was completed within 10 min and 25 min, respectively. The area under the aqueous humor concentration vs. time curve (AUC(0-t)) and maximum concentration (C(max)) values of gel group was 2.70-fold and 1.79-fold higher than that of control group. Additionally, clinical examination showed that SIN suppressed inflammation in EAAU.
Conclusions: These results support the potential applications of SIN in situ gel for uveitis treatment.
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| http://dx.doi.org/10.1016/j.intimp.2013.05.020 | DOI Listing |
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