THEME: "Experimental Challenges in Drug Delivery and Nanomedicine"
Capstone Development Services, USA
Title: Development, Evaluation and Application of Insulin Solution and Film Dosage Forms for Sublingual Administration
Dr. Anuja Paprikar endeavors to apply her accumulated experience in the field of in vitro permeation studies to support the design and execution of studies for generic topical drug development in her current role. Although she has gained experience in formulation and characterization of small as well as large molecules, the aim of her studies presented here was to develop and evaluate a feasible formulation approach for insulin sublingual administration.
The major barrier for sublingual absorption of large molecules like insulin is low permeability owing to the hydrophilic nature of insulin. One approach to overcome this barrier is to sublingually co-administer insulin with permeation enhancers (HP?CD and poloxamer 188). In vitro performance of permeation enhancers was screened across cellulose acetate membrane to select the concentrations of both enhancers, which were further evaluated across four models (MatTek tissue model, MDCK cell line, rat and porcine esophagus). The insulin solution with combination of HP?CD (5%) and poloxamer 188 (0.5%) indicates higher permeation as compared to that of only insulin across all the four models. Subsequently, porcine esophagus was selected as a tool for in vitro permeation studies for sublingual insulin solution. Furthermore, insulin-induced hypoglycemic effect was observed for insulin solution formulations with combination of HP?CD and poloxamer 188 after sublingual administration to Sprague-Dawley rats. An increase in dose of insulin from 5, 10, and 15 IU/kg along with HP?CD and poloxamer 188, maximum reduction of glucose level increased. After exploring the feasibility of HP?CD and poloxamer 188 for sublingual insulin solution administration, permeation of insulin solution was optimized using three-level resolution III fractional factorial design. In this design, the independent (X1: concentration of insulin; X2: concentration of HP?CD; X3: concentration of poloxamer 188) and dependent (Y: cumulative amount permeated at 60 minutes) variables were used. Based on the generated equation from this design, not only contour and interaction plots were generated but also an optimized formulation, and two checkpoint formulations were obtained to validate the design. Thereafter, insulin at three doses for the optimized formulation and safety of permeation enhancers was evaluated. Based on the optimized sublingual insulin solution, polymeric sublingual films were formulated and evaluated. The sublingual insulin films were found to have comparative mechanical properties to that of commercial film (Listerine®). Based on in vitro dissolution and in vitro permeation, it can be concluded that the film on dissolution could behave like insulin solution and hence is a feasible approach for sublingual administration.