Fabrication of lipidic nanocarriers of loratadine for facilitated intestinal permeation using multivariate design approach

Abstract

In this investigation, multivariate design approach was employed to develop self-nanoemulsifying drug delivery system (SNEDDS) of loratadine and to exploit its potential for intestinal permeability. Drug solubility was determined in various vehicles and existence of self-nanoemulsifying region was evaluated by phase diagram studies. The influence of formulation variables X1 (Capmul MCM C8) and X2 (Solutol HS15) on SNEDDS was assessed for mean globule sizes in different media (Y1-Y3), emulsification time (Y4) and drug-release parameters (Y5-Y6), to improve quality attributes of SNEDDS. Significant models were generated, statistically analyzed by analysis of variance and validated using the residual and leverage plots. The interaction, contour and response plots explicitly demonstrated the influence of one factor on the other and displayed trend of factor-effect on responses. The pH-independent optimized formulation was obtained with appreciable global desirability (0.9266). The strenuous act of determining emulsification time is innovatively replaced by the use of oil-soluble dye to produce visibly distinct globules that otherwise may be deceiving. TEM images displayed non-aggregated state of spherical globules (size < 25 nm) and also revealed the structural transitions occurring during emulsification. Optimized formulation exhibited non-Newtonian flow justified by the model-fit and also presented the stability to dilution effects and thermodynamic stress testing. The ex vivo permeation study using confocal laser scanning microscopy indicate strong potential of rhodamine 123-loaded loratadine-SNEDDS to inhibit P-gp efflux and facilitate intestinal permeation. To conclude, the effectiveness of design yields a stable optimized SNEDDS with enhanced permeation potential, which is expected to improve oral bioavailability of loratadine.

Solid Self-Nano Emulsifying Nanoplatform Loaded with Tamoxifen and Resveratrol for Treatment of Breast Cancer

“…It has been reported in the literature that the surfactant with an HLB value ranging from 10 to 17 enhanced the drug absorption and intestinal penetration by inhibiting the efflux pump, which might be due to the penetration and adsorption of the surfactant molecule on the surface of the efflux pump and disorienting the intestinal membrane. In this study, the permeation of SNEDDS increased in comparison to the suspension due to the presence of the surfactant Tween 80 (with HLB 15) in the SNEDDS [ 84 ]. Moreover, the droplet size in the nanometric range (<200 nm) could also be the reason for enhanced permeation as the smaller droplet can easily permeate via the intestinal wall.…”

Preparation, Optimization and In vitro Evaluation of Glipizide Nanoparticles Integrated with Eudragit RS-100

“…The relationship between the formulation variables and the responses in terms of coded factors is represented by the following equations [29, 30].…”

Development of Piperine-Loaded Solid Self-Nanoemulsifying Drug Delivery System: Optimization, In-Vitro, Ex-Vivo, and In-Vivo Evaluation

“…With oral administration, SNEDDS comes in contact with stomach fluid and is automatically self-emulsified with globule size <100 nm in peristalsis movement, which leads to solubilization of the drug, increases the gastric stability, and absorbs directly through the lymphatic way, reducing the first-pass effect, and hence increasing the bioavailability. However, there is a compatibility issue with hard/soft gelatin capsule; SNEDDS transformed into solid SNEDDS (S-SNEDDS) to improve the patient compliance, ease of production, scale-up, and transportation [18].…”