Open AccessAdrenaline (epinephrine) microcrystal sublingual tablet formulation: enhanced absorption in a preclinical model
Author(s) -
RawasQalaji Mutasem,
Rachid Ousama,
Mendez Belacryst A.,
Losada Annette,
Simons F. Estelle R.,
Simons Keith J.
Publication year - 2015
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1111/jphp.12312
Subject(s) - cmax , anaphylaxis , epinephrine , medicine , sublingual administration , placebo , absorption (acoustics) , pharmacokinetics , anesthesia , pharmacology , intramuscular injection , allergy , immunology , materials science , alternative medicine , pathology , composite material
Objectives 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 ( E pi‐ 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 E pi‐ MC 20 mg RDSTs and E pi 40 mg RDSTs was evaluated in rabbits. E pi 0.3 mg intramuscular (IM) injection in the thigh and placebo RDSTs were used as positive and negative controls, respectively. Key findings E pi mean (standard deviation) area under the plasma concentration vs time curves up to 60 min and C max from E pi‐ MC 20 mg and E pi 40 mg RDSTs did not differ significantly ( P > 0.05) from E pi 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). Conclusion E pi‐ MC RDSTs facilitated a twofold increase in E pi 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.