Scale Up of Doxycycline Hydrochloride Lipomer By Nanoprecipitation Using An Air Atomization Technique

The present study discusses scale up of asymmetric doxycycline hydrochloride (DH) LIPOMER (lipid polymer nanostructures) by nanoprecipitation. A solution of Doxycycline hydrochloride , Glyceryl monostearate and Gantrez AN119 in tetrahydrofuran was added to a non solvent phase comprising Isopropyl alcohol and water, under stirring to obtain doxycycline hydrochloride LIPOMER. At the 1X (400mg solids) scale the process was optimized to increase solute concentration and solvent to non solvent ratio while decreasing total solvent volume. At 10X scale varying the agitator speed, agitator type and number of baffles, at a maximum addition rate of 4mL/min, particles with an average size of ~455 nm were obtained with a 45° pitched six blade turbine agitator and baffles. Using the principle of geometric similarity the 10X batch, gradually scaled up to 240X (96 gm solids), revealed average particle size in the range 454 to 510 nm with >80% entrapment efficiency (EE).Using air atomization introducing small globules of the solvent phase (100 mL/min), in to the non solvent phase enabled  a size of ~340 nm with 84%  EE at  120X and 240X. DH LIPOMER exhibited good stability and asymmetric shape. More importantly LIPOMER in the desired size range (~300-600nm) for RES uptake was optimized.  Air atomization presents a simple and practical approach for scaleup of nanoparticles by nanoprecipitation.