Studies On Ribavirin In Situ Thermosensitive Gel

In situ thermosensitive gels refer to the polymer solutions can be administrated as liquid , which undergo a phase transition to a non-crosslinked semisolid gel upon exposure to physiological enviroments. Most of the applications of the in situ thermosensitive gels are concerned with opthalmic disease treatment for its convenient administration combined with the favorable ocular residence time. Ribavirin(RBVR), an antiviral agent of nucleoside analog, has wide efficacy against virus and restrains lots of DNA and RNA copy. Ribavirin has stronger activity and wider applications in the clinic and less side-effects. We selected Ribavirin as a model drug to develop a kind of in situ thermosensitive gels for ophthalmic use.HPLC methods was developed for analysing the drug release from Ribavirin in situ thermosensitive gels and utilized to determine the Ribavirin concentration in situ thermosensitive gels. Ribavirin is freely soluble in water and simulated tear fluid (STF) and the apparent partition coefficient in n-octanol/water system is about 0.055.The methods were developed for measurment the gelation temperature(GT) and viscosity. The reversible gelation behaviors of poloxamer 407(P407)solutions showed strong concentration dependency. The reversible gelation behaviors couldn't occur when the concentration of poloxamer 407 less 15%. GT was adjusted by incorporating P188 and NaCl. The phase transition process of poloxamer solution was completed in 3-5 ℃ and exhibited exponential increase of viscosity with temperature; the gelation mechanism was not changed by incorporating P188. The fitted equation was established for the GT with the concentration of poloxamer solutions.GT was enhanced about 5-10℃ after being diluted by STF. The fitted equation was established for the GT with the concentration of poloxamer solutions after diluted by STF. An optimized formulation was freely flowing liquid at 27.1℃ and converted to a firm gel...