In vitro and in vivo evaluation of an in situ forming gel system for sustained delivery of Florfenicol

The objective of this study was to develop an injectable in situ forming gel system based on Poloxamer for sustained release of Florfenicol (FFC). The formulations were prepared containing certain amounts of Poloxamer 407 (P407) and Poloxamer 188 (P188) alone or with hydroxylpropyl methylcellulose (HPMC), sodium carboxymethyl cellulose (CMC-Na), or polyvinyl pyrrolidone (PVP) as polymer additives. The optimal formulation was chosen according to in vitro parameters (gelation temperature, gelation time, pH value, viscosity, and in vitro release). Then the FFC in vivo pharmacokinetic character of the optimal formulation was investigated in dogs with a single dose of 50mg/kg b.w. under s.c. injection. In vitro release studies, all formulations containing polymer additives had prolonged release time and decreased initial burst to some extent. The optimal formulation containing 0.15% HPMC showed a best sustained release profile for about 128h with the lowest initial burst in vitro (<40% in 24h). In vivo, the 20% FFC in situ forming gel provided prolonged drug release time within the therapeutic range for about 100h, with stable plasma levels and elimination half-life (t(1/2z)) nine times higher than the control formulation. In conclusion, in situ forming gel is an attractive alternative for FFC sustained release system.