Statistical optimization of insulin-loaded Pluronic F-127 gels for buccal delivery of basal insulin

The principle of statistical optimization was employed to fabricate insulin-loaded Pluronic F-127 (PF-127) gel formulations having the potential for buccal delivery of basal insulin. A two-level resolution III fractional factorial design was applied to simultaneously evaluate five independent formulation variables: PF-127 concentration, insulin concentration, sodium sulfate concentration, hydroxypropylmethyl cellulose (HPMC) concentration, and presence of sodium glycocholate. The amount of insulin released and permeated from gels as well as gelation time and mucoadhesion force of gels were measured and used as dependent response variables for formulation optimization. Optimization of a gel formulation was achieved by applying constrained optimization via regression analysis. In vitro permeation flux of insulin from the optimized formulation through procine buccal mucosa was 93.17 (+/- 0.058, n = 3) mu g/cm(2). Plasma insulin levels following buccal administration of the optimized formulation at 10, 25 and 50 IU/kg to healthy rats were found to be dose dependent and basal insulin levels were maintained at least for 8 h. Furthermore, continuous hypoglycemia for at least 8 h was observed with 89%, 51% and 25% of blood glucose reduction, respectively, for these three doses. The results of this investigation conclude the feasibility of development of optimized buccal insulin-loaded Pluronic F-127 gels for basal insulin delivery.