Improved oral bioavailability of poorly water-soluble vorinostat by self-microemulsifying drug delivery system

Abstract

Background Vorinostat is a histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) with anticancer properties. However, it is plagued by low water solubility, low permeability (BCS class IV drug), and suboptimal pharmacokinetics. The purpose of the present study was to develop a self-microemulsifying drug delivery system (SMEDDS) to enhance the oral bioavailability of vorinostat. Capryol 90, labrasol, and polyethylene glycol (PEG 400) were selected as oil phase, surfactant, and co-surfactant, respectively. The vorinostat self-microemulsifying drug delivery systems were tested for self-microemulsifying time, phase separation, effect of pH, droplet size, zeta potential, dilution study, Fourier-transform infrared (FT-IR) spectroscopy analysis, and field emission scanning electron microscopy (FESEM). A rat model in vivo pharmacokinetic study was conducted for the optimized formulation against vorinostat pure drug powder. Results The results from the characterization studies showed that the optimized formulation (F7) self-microemulsification time was 1.4 ± 0.05 min and no precipitation or phase separation was observed. The mean droplet size, polydispersity index (PDI), and zeta potential of the optimized formulation (F7) were found to be 272.9 ± 82.7 nm, 0.415, and − 57.2 mV, respectively. The pharmacokinetic parameters of the optimized formulation (F7) showed a 1.6-fold increase in maximum concentration (Cmax) and a 3.6-fold increase in area under the curve (AUC(0−∞)), in comparison with pure drug in suspension. Conclusions The findings suggest that SMEDDS formulation could be an effective method for increasing the oral bioavailability of vorinostat, which is poorly water soluble.

Fabrication, Characterization and In Vitro Cell Cytotoxicity of ZnO Nanoparticles on MDA‐MB 231 Breast Cancer Cell Line

“…The UV absorption spectra were measured between wavelengths of 200–400 nm. The maximum absorption wavelength (λ max ) and the spectrum of absorbance against wavelength were recorded [23] …”

“…The maximum absorption wavelength (λ max ) and the spectrum of absorbance against wavelength were recorded. [23] Fourier transform infrared spectroscopy (FTIR) FTIR Spectrophotometer (Nicolet iS5, Thermo Fisher Scientific, US) was utilized to study the functional groups of ZnO-NPs. The spectrophotometer was set at 20 sample scans, a laser frequency of 15798 cm À 1 and a resolution of 4.0.…”

Review: emulsion techniques for producing polymer based drug delivery systems

“…Vorinostat-loaded SMEDDS formulation exhibited the significant performance in solubility and bioavailability as compared to Vorinostat-unloaded SMEDDS. The SMEDDS gave a higher absorption rate in GI thanks to opening the tight junctions in the intestine, leading to an increase in intestinal wall permeability [33]. CCL5 nanoparticles did not cause acute toxicity in rats when used at doses higher than 1000 mg/kg.…”

“…Ashok Kumar Janakiraman et al reported that the SMEDDS containing capryol 90, PEG 400, and labrasol could remarkably improve the stability and solubility of Vorinostat drug [33]. Vorinostat was dissolved in capryol 90 and mixed with a vortex mixer for 20 minutes to form an oily phase.…”

A review of strategies for the development of solid self-microemulsifying drug delivery system

“…Liquid formulations are prone to stability issues, such as drug degradation, phase separation, and leakage. By converting SMEDDS into solid dosage forms such as powders or pellets, this drug delivery system provides improved stability and convenience in handling, storage, and transportation [7] .  Improved Patient Compliance Solid dosage forms, such as tablets or capsules, are commonly used in oral drug delivery due to their ease of administration and patient acceptance.…”