Preparation of hydrocortisone nanosuspension through a bottom-up nanoprecipitation technique using microfluidic reactors

In this work, the possibility of bottom-up creation of a relatively stable aqueous hydrocortisone nanosuspension using microfluidic reactors was examined. The first part of the work involved a study of the parameters of the microfluidic precipitation process that affect the size of generated drug particles. These parameters included flow rates of drug solution and antisolvent, microfluidic channel diameters, microreactors inlet angles and drug concentrations. The experimental results revealed that hydrocortisone nano-sized dispersions in the range of 80-450 nm were obtained and the mean particle size could be changed by modifying the experimental parameters and design of microreactors. The second part of the work studied the possibility of preparing a hydrocortisone nanosuspension using microfluidic reactors. The nano-sized particles generated from a microreactor were rapidly introduced into an aqueous solution of stabilizers stirred at high speed with a propeller mixer. A tangential flow filtration system was then used to concentrate the prepared nanosuspension. The nanosuspension produced was then characterized using photon correlation spectroscopy (PCS), Zeta potential measurement, transmission electron microscopy (TEM), differential scanning calorimetry (DSC) and X-ray analysis. Results showed that a narrow sized nanosuspension composed of amorphous spherical particles with a mean particle size of 500 +/- 64 nm, a polydispersity index of 0.21 +/- 0.026 and a zeta potential of -18 +/- 2.84 mV was obtained. Physical stability studies showed that the hydrocortisone nanosuspension remained homogeneous with slight increase in mean particle size and polydispersity index over a 3-month period. (C) 2009 Elsevier B.V. All rights reserved.