Solid Lipid Nanoparticles Of Coenzyme Q10 By Microemulsion And Supercritical Fluid Techniques

The present work explores the possibility of formulating an oral coenzyme Q10(CoQ10) delivery system by using the currently accepted microemulsion technique and the novel supercritical fluid technology for solid lipid nanoparticle(SLN) preparation.Four different formulations(F₁ - F₄) were investigated for SLN dispersions and o/w microemulsions by using the microemulsion technique.SLN dispersions were characterized by particle size,particle size distribution,stability under storage.Results indicate that for formulations F₂ and F₃ more than 50%of the particles are below 200 nm. The formulation of SLN dispersion from F₃ consists of tripalmitin,CoQ10,Tween^?20, ethanol,span 20,while the formulation of microemulsion F₂ consists of tripalmitin,CoQ10, Tween^?80,lecithin,poloxamer F68.The mean particle size measured by laser diffractometry(LD) for the SLN dispersions from F₃ is 170±10 nm with a narrow particle distribution of polydispersity index,0.145±0.015,while the mean particle size measured by LD for the SLN dispersions from F₂ is 155±15 nm with a narrow particle distribution of polydispersity index,0.24±0.07.The stability of the prepared microemulsions remains unchanged,however,the prepared SLN suspensions at room temperature shows obvious instability after 14 days or 30 days storage.The microemulsion technique could prepare high quality SLNs loading lipophilic drugs;it is simple,available method to produce SLNs, while limited by the applied ultrasonic homogenizer with large amount of water.PGSS(Particles from gas-saturated solutions) technology with carbon dioxide(CO₂) was used to produce solid lipid particles of CoQ10.The microemulsion with the best formulation F₂ was used in this study.The effects of pre-expansion pressure(10 to 25 MPa),flow rate of the microemulsion(0.1 to 0.5 ml min^-1),and different collection units(50 mg ml^-1 PEG 6000 solution at room temperature(25±2℃),liquid nitrogen,cold 50 mg ml^-1 PEG 6000 solution(0±2℃),and air) at fixed nozzle size(100μm) and pre-expansion temperature (75℃,the same temperature for preparing microemulsions) on the particle size and particle size distributions were investigated.Results evidence that both nanoparticles(SLNs) and microparticles are produced at different pre-expansion pressures,flow rates and with different collection units.The optimum operating conditions for high percentage SLN(50%) in the produced particles are:high pre-expansion pressure of 15 MPa,microemulsion flow rate of 0.1 ml min^-1,collection of particles in cold PEG 6000 solution.Although microparticles and SLN were produced by the PGSS technique,the SLNs are less than 400nm(mean size less than 200nm),while the microparticles are larger than 2000nm (mean size about 10000 nm or 10μm).This clearly shows that the produced SLNs are expected to be separated easily by using traditional separation techniques.The proposed PGSS technique can continuously and conveniently manufacture SLNs from treating microemulsion without additional use of water with a high productivity.But the drawback is that the microemulsion cannot be transformed totally into SLNs directly.