Formulation development and evaluation of insulin-loaded Pluronic gels for buccal drug delivery.

摘要

Basal insulin (0.5-1 IU/hr) produced from human pancreas maintains normal blood glucose level (70-120 mg/dL) between meals. In diabetic patients, this insulin production is disrupted requiring insulin injections. Buccal delivery of insulin may be a painless alternative to injection.;The objective of this project was to study insulin-loaded Pluronic F127 gel formulations as a vehicle of basal insulin delivery via the buccal route. The effects of formulation variables (Pluronic F127, insulin, salts, polymers, permeation enhancers) and temperature on the release and permeation of insulin from the Pluronic F127 gel formulations were analyzed. Increase in Pluronic F127 concentration increased viscosity and mucoadhesion force, while reducing gelation time, release and permeation of insulin. Although increase in insulin concentration did not produce any change in viscosity, gelation time and mucoadhesion force, it increased insulin release and permeation. Salts, in general, increased viscosity and reduced gelation time, release and permeation of insulin. They did not affect the mucoadhesion force of the gel formulations. Hydrophilic polymers (polyethylene glycol and polyvinyl pyrrolidone) decreased viscosity and increased gelation time, release and permeation properties, without affecting the mucoadhesion force. Hydrophobic polymers (poly(vinyl)alcohol, methylcellulose, and hydroxypropylmethyl cellulose) decreased all response parameters, except mucoadhesion force, which increased in their presence. All permeation enhancers decreased viscosity, increased gelation time, release and permeation rates of insulin, but did not have any effect on mucoadhesion force. Increase in temperature enhanced the release and permeation of insulin from Pluronic F127 gels.;A two-level resolution III fractional factorial design generated the optimized formulations with desired permeation, gelation time and mucoadhesiveness. Agreement with respect to all response parameters was observed between the proposed model and experiments. Analysis of kinetic release data showed release of insulin from Pluronic F127 gels through a combination of gel dissolution and insulin diffusion. Basal level of insulin was maintained in rats for 8 hours. Stability studies showed 96.12% residual insulin after 10 months in the final optimized gel formulation stored at 4-5°C.;Hence, a stable and statistically optimized Pluronic F127 gel formulation has been obtained, which has the potential to deliver basal insulin in diabetic patients.