Study On The Nasal Thermoreversible Gels Of Ribavirin

The purpose of this paper was to develop a thermosensible in situ gel including ribavirin(RBVR) for intranasal administration. Drug delivery through the nasal route has received a lot of attention recently because of its advantages such as rapid absorption, avoidance of first-pass elimination and so on. Poloxamer 407, a thermosensible high molecular material, was introduced into nasal drug delivery system. This material can make the nasal preparation liquid state at room temperature and a semisolid gel at nasal temperature(33℃). Thermosensible gel formulation can prolong the nasal residence time of drug greatly except for the merits of traditional nasal preparation.The properties about RBVR were studied as an essential part of preformulation. The oil/water partition coefficient of RBVR were determined:P=0.062(n-octyl alcohol/water). The thermodynamic [gelation(T₁) and gel melting(T₂)] and rheological [viscosity (η)] properties of nasal thermoreversible gels were studied. The result indicated the thermodynamic T₁ and T₂ and rheological properties η of nasal thermoreversible gels significantly showed concentration-dependent of poloxamer 407;and it is different that the drug of RBVR and the formulation additives [poloxamer 188 (P188),PEG6000,BKC andNaCl] effect on T₁,T₂ and η of nasal thermoreversible gels.That can be based on these studies to design the formulation of nasal thermoreversible gels of RBVR.The formulation screening was performed by taking sol-gel transition temperature and in vitro release as indices. The best formulation of RBVR thermosensible gel was 0.5% RBVR + 20%P407+ 2%P188 + 2% PEG6000 + 0.02% BKC + 0.9% NaCl. In this formulation, the sol-gel transition temperature was between 32～33℃ and the RBVR release from thermosensible gel was accelerated obviously. The in vitro release of RBVR...