Optimized self-microemulsifying drug delivery system improves the oral bioavailability and brain delivery of coenzyme Q₁₀

Abstract

Our study aimed to develop a self-microemulsifying drug delivery system for the poorly aqueous-soluble drug Coenzyme Q 10 , to improve the dissolution and the oral bioavailability. Excipients were selected based on their Coenzyme Q 10 solubility, and their concentrations were set for the optimization of the microemulsion by using a D-optimal mixture design to achieve a minimum droplet size and a maximum solubility of Coenzyme Q 10 within 15 min. The optimized formulation was composed of an oil (omega-3; 38.55%), a co-surfactant (Lauroglycol® 90; 31.42%), and a surfactant (Gelucire ® 44/14; 30%) and exhibited a mean droplet size of 237.6 ± 5.8 nm and a drug solubilization (at 15 min) of 16 ± 2.48%. The drug dissolution of the optimized formulation conducted over 8 h in phosphate buffer medium (pH 6.8) was significantly higher when compared to that of the Coenzyme Q 10 suspension. A pharmacokinetic study in rats revealed a 4.5-fold and a 4.1-fold increase in the area under curve and the peak plasma concentration values generated by the optimized formulation respectively, as compared to the Coenzyme Q 10 suspension. A Coenzyme Q 10 brain distribution study revealed a higher Coenzyme Q 10 distribution in the brains of rats treated with the optimized formulation than the Coenzyme Q 10 suspension. Coenzyme Q 10 -loaded self microemulsifying drug delivery system was successfully formulated and optimized by a response surface methodology based on a D-optimal mixture design and could be used as a delivery vehicle for the enhancement of the oral bioavailability and brain distribution of poorly soluble drugs such as Coenzyme Q 10 .

Review: emulsion techniques for producing polymer based drug delivery systems

“…The nanoparticles exhibited a high accumulation in SCC7 tumor tissue in rats after intravenous injection (Figure 16). The bioavailability of coenzyme Q 10 loaded by the SMEDDS was also improved as compared to coenzyme Q 10 unloaded by the SMEDDS [32]. The concentration of coenzyme Q 10 in blood when administrated with coenzyme Q 10 SMEDDS was much higher than that when administrated with coenzyme Q 10 suspension (Figure 17).…”

“…Thapa Chhitij et al have optimized the conditions for the preparation of SMEDDS containing coenzyme Q 10 [32]. By D-optimal mixture design, the authors found the optimal formulation for SMEDDS based on the solubility and concentration of these systems.…”

COQ8A-Ataxia as a Manifestation of Primary Coenzyme Q Deficiency

“…These findings suggested that in primary coenzyme Q10 deficiency, CoQ10 distribution in the brain may be improved by the administration of LDLR inhibitors or by interventions to stimulate the luminal activity of SR-B1 transporters [ 60 ]. Better CoQ10 brain distribution and peak plasma concentration were achieved in rat models using a self-microemulsifying drug delivery system of CoQ10 compared to the coenzyme Q10 suspension [ 61 ]. Sheykhhasan et al reported a positive effect of CoQ10 drug delivery with the use of exosomes derived from adipose-derived stem cells (ADSCs-Exo) in a rat model of Alzheimer’s disease [ 62 ].…”

Hyaluronic Acid Poly(glyceryl)10-Stearate Derivatives: Novel Emulsifiers for Improving the Gastrointestinal Stability and Bioaccessibility of Coenzyme Q10 Nanoemulsions

“…Q10 bioaccessibilities were also found as 63.75 ± 0.91 and 46.83 ± 1.27% in yogurts enriched with emulsified Q10, and γ-cyclodextrin/Q10 complex, respectively. Consequently, to overcome the drawbacks of Q10 and expand its applications to relevant fields, researchers are developing different strategies to overcome these challenges, including encapsulating the Q10 in delivery systems, such as nanoemulsions, nanoparticles, microparticles, liposomes, and cyclodextrins. , In this study, we focused on the utilization of oil-in-water (O/W) nanoemulsions to encapsulate Q10.…”

“…Consequently, to overcome the drawbacks of Q10 and expand its applications to relevant fields, researchers are developing different strategies to overcome these challenges, including encapsulating the Q10 in delivery systems, such as nanoemulsions, nanoparticles, microparticles, liposomes, and cyclodextrins. 16,17 In this study, we focused on the utilization of oil-in-water (O/W) nanoemulsions to encapsulate Q10. Oil-in-water nanoemulsions are usually prepared by homogenizing an oil phase with a water phase containing a suitable emulsifier.…”