title: Adrenaline (epinephrine) microcrystal sublingual tablet formulation: enhanced absorption in a preclinical model.
abstract: OBJECTIVE
  For anaphylaxis treatment in community settings, adrenaline (epinephrine) administration using an auto-injector in the thigh is universally recommended. Despite this, many people at risk of anaphylaxis in community settings do not carry their prescribed auto-injectors consistently and hesitate to use them when anaphylaxis occurs.The objective of this research was to study the effect of a substantial reduction in adrenaline (Epi) particle size to a few micrometres (Epi microcrystals (Epi-MC)) on enhancing adrenaline dissolution and increasing the rate and extent of sublingual absorption from a previously developed rapidly disintegrating sublingual tablet (RDST) formulation in a validated preclinical model.
  
  
  METHODS
  The in-vivo absorption of Epi-MC 20 mg RDSTs and Epi 40 mg RDSTs was evaluated in rabbits. Epi 0.3 mg intramuscular (IM) injection in the thigh and placebo RDSTs were used as positive and negative controls, respectively.
  
  
  RESULTS
  Epimean (standard deviation) area under the plasma concentration vs time curves up to 60 min and Cmax from Epi-MC 20 mg and Epi 40 mg RDSTs did not differ significantly (P > 0.05) from Epi 0.3 mg IM injection. After adrenaline, regardless of route of administration, pharmacokinetic parameters were significantly higher (P < 0.05) than after placebo RDSTs administration (reflecting endogenous adrenaline levels).
  
  
  CONCLUSIONS
  Epi-MC RDSTs facilitated a twofold increase in Epi absorption and a 50% reduction in the sublingual dose. This novel sublingual tablet formulation is potentially useful for the first-aid treatment of anaphylaxis in community settings.
authors.affiliation: College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL, USA.
authors.forename: Mutasem
authors.initials: M
authors.lastname: Rawas-Qalaji
authors.forename: Ousama
authors.initials: O
authors.lastname: Rachid
authors.forename: Belacryst A
authors.initials: BA
authors.lastname: Mendez
authors.forename: Annette
authors.initials: A
authors.lastname: Losada
authors.forename: F Estelle R
authors.initials: FE
authors.lastname: Simons
authors.forename: Keith J
authors.initials: KJ
authors.lastname: Simons
mesh_terms: D000286:Administration, Sublingual; D000707:Anaphylaxis / Q000188:drug therapy; D000818:Animals; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D004837:Epinephrine / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D007273:Injections, Intramuscular; D008657:Metabolic Clearance Rate; D010316:Particle Size; D011446:Prospective Studies; D011817:Rabbits; D013607:Tablets / Q000737:chemistry*
chemical_list: D013607:Tablets; D004837:Epinephrine
keywords: absorption; adrenaline; anaphylaxis; microcrystals; sublingual tablets