Quality by design approach to the development of self-microemulsifying systems for oral delivery of teriflunomide: design, optimization, and in vitro and in vivo evaluation

Abstract

Objective The present study was aimed at the development of a self-microemulsifying drug delivery system (SMEDDS) for the low water-soluble drug using quality by design (QbD) to enhance the bioavailability of drugs. Experimental work The components of the SMEDDS were preliminarily screened using the pseudoternary phase diagram as a solubility study. The patient-centric, quality target product profile, and critical quality attributes were earmarked. Preformulation studies were performed along with an initial risk assessment that facilitated the selection of lipids (i.e. Sefsol 218), surfactants (i.e. Acrysol EL-135), and cosurfactants (i.e. PEG 400) as Critical Material Attributes for the formulation of SMEDDS. Extreme vertices mixture design, given its utility and the pertinence to the design issue in hand, was chosen for the study. The various responses selected for this design were drug release at 20 min (%), transmittance (%), emulsification time (s), and globule size (nm). Eleven distinct formulations were prepared and measured to check the model fit. The optimization and model validation were finished by directing experimental runs. Results and discussion Sefsol 218 (oil), Acrysol EL-135 (surfactant), and PEG 400 (cosurfactant) showed the highest solubility. The fourier transform infrared spectroscopy (FTIR) study suggested that there may be no significant difference in the characteristic’s peak at a wavenumber of the drug in the presence of excipients. The studies have shown that the application of extreme vertices mixture design and the development of formulation in QbD resulted in a powerful and viable technique for improving the bioavailability of the drug. This was confirmed by the characteristics’ studies of the optimized batch like in vitro drug release in 20 min (73.44%), drug content (99.3%), emulsification time (25 s), transmittance (99.5%), droplet size (16.64 nm), polydispersibility index 0.170, and zeta potential −9.74 mV. A great agreement was observed among the predicted and experimental values for the average globule size and percentage of the drug released in 20 min. Furthermore, the optimal SMEDDS formulation exhibited fundamentally higher, extreme-plasma concentration, and area under the curve values a twofold higher value (P<0.05) than the teriflunomide suspension. Conclusion In summary, the present studies report successful QbD-oriented development of a novel oral teriflunomide-loaded SMEDDS formulation to noticeably improve the bioavailability of low water-soluble drugs.