Comparative study on solid self-nanoemulsifying drug delivery and solid dispersion system for enhanced solubility and bioavailability of ezetimibe

Abstract

Background The objective of this study was to compare the physicochemical characteristics, solubility, dissolution, and oral bioavailability of an ezetimibe-loaded solid self-nanoemulsifying drug delivery system (SNEDDS), surface modified solid dispersion (SMSD), and solvent evaporated solid dispersion (SESD) to identify the best drug delivery system with the highest oral bioavailability. Methods For the liquid SNEDDS formulation, Capryol 90, Cremophor EL, and Tween 80 were selected as the oil, surfactant, and cosurfactant, respectively. The nanoemulsion-forming region was sketched using a pseudoternary phase diagram on the basis of reduced emulsion size. The optimized liquid SNEDDS was converted to solid SNEDDS by spray drying with silicon dioxide. Furthermore, SMSDs were prepared using the spray drying technique with various amounts of hydroxypropylcellulose and Tween 80, optimized on the basis of their drug solubility. The SESD formulation was prepared with the same composition of optimized SMSD. The aqueous solubility, dissolution, physicochemical properties, and pharmacokinetics of all of the formulations were investigated and compared with the drug powder. Results The drug existed in the crystalline form in SMSD, but was changed into an amorphous form in SNEDDS and SESD, giving particle sizes of approximately 24, 6, and 11 µm, respectively. All of these formulations significantly improved the aqueous solubility and dissolution in the order of solid SNEDDS ≥ SESD > SMSD, and showed a total higher plasma concentration than did the drug powder. Moreover, SESD gave a higher area under the drug concentration time curve from zero to infinity than did SNEDDS and SMSD, even if they were not significantly different, suggesting more improved oral bioavailability. Conclusion Among the various formulations tested in this study, the SESD system would be strongly recommended as a drug delivery system for the oral administration of ezetimibe with poor water solubility.

<p>Self-microemulsifying drug delivery system (SMEDDS) for improved oral delivery and photostability of methotrexate</p>

“…Limited solubility can lead to insufficient dissolution and further reduce the bioavailability of a drug 7,8. As a result, a variety of effort has been made to enhance the oral bioavailability of poorly water soluble drugs through lipid based emulsion systems, specifically the self-emulsifying drug delivery system (SEDDS) 9–12. SEDDSs are defined as homogeneous mixtures of natural or synthetic oils, surfactants, and co-surfactants that easily form emulsion upon mild agitation and generate a high surface area of interactions between the SEDDS formulation and the gastrointestinal (GI) fluid 13.…”

Formulation and Evaluation of Linum usitatissimum Mucilage-Based Nanoparticles for Effective Delivery of Ezetimibe

“…The spectra do not show any shift in drug peak, which infers that the drug and other formulation excipients showed no interaction chemically in the fabricated formulations when prepared by both techniques. 51 …”

A novel solid self-nanoemulsifying drug delivery system (S-SNEDDS) for improved stability and oral bioavailability of an oily drug, 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol

“…In this study, in order to overcome these problems of oily PLAG, a S-SNEDDS, a solid dosage form, was developed with a surfactant, hydrophilic polymer, antioxidant, and carrier using a spray-drying technique. In general, liquid SNEDDS, nanoemulsion systems, have been prepared with surfactant and oil (Rashid et al., 2015a ). However, the oil is not necessary in the preparation of PLAG-loaded SNEDDS, because PLAG is an oily drug.…”