FABRICATION AND CHARACTERIZATION OF EPINEPHRINE NANOCRYSTALS USING TOP-DOWN TECHNIQUE

Objective. To fabricate and characterize epinephrine bitartrate nanocrystals (EpiBit-NCs) using Microfluidizer. Background. Epinephrine(Epi) 0.3mg IM injection is the drug of choice for the treatment of anaphylaxis in community sittings. Previously, we showed that Epi 40mg rapidly disintegrating sublingual tablets (RDSTs) is bioequivalent to Epi 0.3mg IM injection in a rabbit model. We hypothesized that significant reduction in the Epi particle size will significantly increase Epi dissolution and absorption and permit for the reduction of Epi sublingual dose. Methods. EpiBit NCs were prepared using LV-1/Microfluidizer. EpiBit 0.7mg/ml, 1.4mg/ml, 2.8mg/ml, 3.5mg/ml, and 4.5mg/ml were suspended in isopropyl alcohol (n=3) and processed at 15,000, 25,000, or 30,000Psi for 4 cycles. Mean particles size distribution (PSD) and zeta potential (ZP) were measured after each cycle using Zetasizer(n=3). Reproducibility and fabrication yield were calculated(n=5). Results. Mean(SD) PSD of EpiBit before processing was 131.8±10.5μm. Processing EpiBit 0.7mg/ml, 1.4mg/ml, 2.8mg/ml, 3.5mg/ml, and 4.5mg/ml for 1 cycle at 30,000Psi resulted in PSD and ZP of 709±288nm and -14±6mV, 665±47nm, 249±38nm and -28±2mV (fabrication yield 36±6%), 1211±389nm and -16±2mV, and 1091±43nm and -28±1mV, respectively. Processing EpiBit 2.8mg/ml for 2, 3, 4 cycles resulted in PSD of 827±114nm, 971±124nm, and 976±163nm, respectively. Processing EpiBit 2.8 mg/ml for 1 cycle at 25,000 or 15,000Psi resulted in PSD and ZP of 603±169nm and -9±4mV, and 649±473nm and -12±7mV, respectively. Conclusion. The fabrication of the EpiBit NC using LV-1 Microfluidizer was feasible. Particles size was reduced 135 fold. EpiBit NC as RDSTs have the potential to enhance the sublingual absorption of Epi. Grants. This study was funded by the Health Professions Division Grant and the President\u27s Faculty Research & Development Grant, Nova Southeastern University