Development and Characterization of Novel Solid Self Nanoemulsifying Drug Delivery System of Fimasartan

Abstract

Purpose

The objective of the present study was to prepare a solid self-nano emulsifying drug delivery system (S-SNEDDS) of Fimasartan Potassium Trihydrate (FPT), a poorly water-soluble antihypertensive agent.

Methods

Equilibrium Solubility study and ternary phase diagram study were conducted for screening of excipients. D-optimal Mixture design was employed to optimise the formulation variables, X₁ (amount of oil; Capmul MCM C8), X₂ (amount of surfactant; Labrasol) and X₃ (amount of co-solvent; Transcutol HP). Self-emulsification time (Y₁), percentage transmittance (Y₂) and mean globule size (Y₃) were set as response variables. Optimised liquid SNEDSS (L-SNEDDS) formulation was further assessed for robustness to dilution, thermodynamic stability study, cell viability and TEM analysis. L-SNEDDS was converted into free flowing powder (S-SNEDDS) by adsorption on the porous carrier like Neusilin US2 and thereafter filled in hard gelatin capsules (HGC). Prepared HGC was further evaluated for in-vitro dissolution, stability and bioavailability study.

Results

The optimized L-SNEDDS formulation consists of 20% oil, 40% surfactant, and 40% co-solvent, demonstrating strong thermodynamic stability and safety for cellular use.TEM analysis demonstrated that the nanoemulsion comprised spherical, uniformly sized globules. When testing the in vitro dissolution of HGC derived from FPT-loaded S-SNEDDS, there was a noticeable increase in the drug's dissolution rate, achieving 98% drug release within 30 min. Additionally, subsequent stability testing in accordance with ICH guidelines over a six-month period indicated that the HGC remained stable, with no significant alterations in its physicochemical characteristics. The bioavailability study indicated a significant enhancement, with a 1.5-fold increase in the relative bioavailability of S-SNEDDS in comparison to the pure drug.

Conclusion

Based on the results obtained, it has been concluded that S-SNEDDS, with its ability to create a nanometric dispersion of controllable size, enhances the solubility, dissolution, bioavailability and stability of the encapsulated FPT drug more effectively than conventional dosage forms.

Present study demonstrated an increase in dissolution and improved bioavailability for FPT. In conclusion, the results of this study indicate the potential use of the developed S-SNEDDS formulation for delivering the active ingredient.