Preparation Of Solid Lipid Nanoparticles In Rectangular Microchannels

Solid lipid nanoparticles (SLNs) were suggested as an alternative drug carrier system with advantages of long-term stability, excellent biocompatibility and controlled release. It can easily be undertaken by oral, dermal, pulmonary route and so on. It is very important to prepare the SLNs with small diameters and narrow size distribution to improve the capability of loaded drugs and more ways of drug delivery.There are numerous methods to prepare SLNs, such as high pressure homogenization, microemulsion, solvent emulsification evaporation and high speed stirring. Hot homogenization is carried out at temperature above the lipid melting point. It can induce the degradation of temperature sensitive drugs or compounds such as proteins and vitamins. Microemulsion has the simple preparation process and less energy but it needs high concentrations of emulsifier. Solvent emulsification -diffusion technique has the problem of solvent residue. In addition, other methods such as solvent emulsification evaporation and ultra sonication have the problems of wide size distribution and low concentration in SLN dispersant system and the accurate control process. Therefore, it is significant to promote new techniques for preparation of SLNs with small sizes and narrow size distribution, which are safety and easy to be controlled accurately.Microchannels have the characteristics of high specific surface area, uniform fluid field and fast mass transfer. Therefore it is expected to prepare the SLNs with small sizes and narrow size distribution in microchannels.This work presents the preparation of SLNs in rectangular microchannels, which are "T" junction and cross-shaped junction. During the experiment process, the lipid solution by dissolving the lipid in a water-miscible organic solvent and the aqueous surfactant solution were passed through the main channel branches respectively. These two liquids met together at the junction and passed along the main channel. The solvent diffused from the lipid solution stream into the aqueous phase, which resulted in the local supersaturation of lipid and thus led to the formation of SLNs. The SLNs flow out of the main channel with the liquid and were collected by conical flask with the magnetic stir set. The mean diameter and the size distribution of the SLNs obtained were measured by dynamic light scattering (DLS) method and the particle morphology was examined by transmission electron microscopy (TEM). The flow behaviors of lipid and aqueous phase zones were measured by a digital inversion microscope system.This work investigates the effect of many factors such as microchannel size, aqueous flow rate, lipid flow rate, the concentration of surfactant and lipid, different solvent and different mixing mode, on the properties of SLNs (the particle size and the size distribution). The effect of slug flow on the particle size and the size distribution was also explored. The formation mechanism of SLNs in the present microchannel system was discussed and analyzed.