Tenth Annual Grant Winners 2009-2010
Andres Malave, Ph.D.
Mutasem Rawas-Qalaji, Ph.D.
Title: Novel approach for the Drug Delivery of Epinephrine for Anaphylaxis Treatment
Anaphylaxis may occur following the exposure to an antigen in susceptible persons. The incidence of anaphylaxis is increasing each year, and fatalities, although preventable, still occur.
Prompt intramuscular injection of epinephrine is the drug of choice. Epinephrine autoinjectors, 0.15 and 0.3 mg, are prescribed for self-administration outside of healthcare facilities. However, they are underutilized when anaphylaxis occurs, mainly due to unavailability or unaffordability.
Because of the invasiveness of the injection, the high cost of autoinjectors, the lack of an adequate dosing mechanism for infants and young children, and the unavailability of autoinjectors in some countries, alternative methods of administration are being explored.
Fast-disintegrating tablets made from epinephrine-loaded nanoparticles have potential as a non-invasive and cost-effective alternative for epinephrine autoinjectors. Loading epinephrine into nanoparticles will increase epinephrine absorption, mask its initial vasoconstricting effect that may limit its absorption, and mask the better taste of epinephrine. The tablets would hopefully provide the convenience of a wide range of doses, especially for children; and pain-free multiple dosing, if required, for out-of-hospital emergency treatment of anaphylaxis.
Recently, we were able to deliver epinephrine through the sublingual route using a novel fast-disintegrating tablet formulation. However, the relative sublingual bioavailability of epinephrine using this tablet formulation was very low. The general aim of this proposal is to formulate tablets that will significantly increase that sublingual epinephrine bioavailability.
Our hypothesis is that loading epinephrine into nanoparticles with specific characteristics, and incorporating penetration enhancers and mucoadhesives, if needed, into the tablet formulation will significantly increase the relative sublingual bioavailability of epinephrine. In the proposed work, different epinephrine nanoparticles will be fabricated using the double emulsion-solvent evaporation method; the diffusion of different epinephrine nanoparticles and the role of mucoadhesives and penetration enhancers will be evaluated ex vivo using diffusion cells; and the stability of epinephrine-loaded nanoparticles in a tablet dosage form will be evaluated.