Fabrication of Epinephrine Nanoparticles Using Microfluidizer Processor for the Treatment of Anaphylaxis

Purpose. Epinephrine was previously formulated into fast-disintegrating sublingual tablets (AAPS PharmSciTech 2006;7(2):41) and the sublingual bioavailability was established in vivo (J Allergy Clin Immunol 2006;117(2):398-403) for the potential first-aid treatment of anaphylaxis. The purpose of this study was evaluate the feasibility of reducing epinephrine particles size using high shear fluid processor (Microfluidizer) to enhance epinephrine sublingual bioavailability. Methods. (-)-Epinephrine (Epi) and (-)- epinephrine (+)-bitartrate (EpiBit) solubility were tested in various solvents as carriers for shear fluid processing. Epi and EpiBit suspensions were processed using M-110P Microfluidizer at 15 to 30 KPsi for several passes. Particles size was measured before and after processing using NiComp 370 and Mastersizer. Epi and EpiBit stability was monitored visually and by FT-IR. Powder was collected by ART bench top lyophilizer. Results. Water and isopropyl alcohol were selected as carriers for Epi and EpiBit respectively. Epi’s particles size was reduced from 32.9±0.3 μm (mean±SD) to 905.9±82 nm and to 273.9±179 nm after one pass at 15 KPsi and 30 KPsi, respectively. EpiBit’s particles size was reduced from 150.7±5.0 μm to 2.0±0.2 μm after 16 passes at 15 KPsi (1 pass) and 25 KPsi (15 passes). After processing, Epi suspension discolored to pinkish- brownish color and EpiBit did not change color. FT-IR spectrums reflected Epi degradation and confirmed EpiBit stability after processing. The process yield for EpiBit was 68%. Conclusion. Size reduction of Epi was achievable but resulted in its degradation. EpiBit was stable during the shear process and the particle size was reduced to 2 μm