US 11,021,437 B2 · Pharmaceutical formulation for sublingual or buccal delivery of epinephrine or a pro-drug thereof

Abstract

The present invention relates to a pharmaceutical composition for the treatment of anaphylaxis formulated for rapid delivery, in one embodiment, the delivery vehicle is a rapidly dissolving film. The films contain an epinephrine or a novel epinephrine pro-drag for fee rapid treatment of anaphylaxis in a patient. This invention relates to pharmaceutical compositions made by modifying the physicochemical properties of epinephrine in order to enhance its permeability through biological membranes (sublingual and buccal membranes). Several prodrugs of epinephrine are shown by modifying the two hydroxyl (phenolic) groups in positions 3 and 4 on the benzene ring, by chemically reacting the two groups with several acid moieties to form an ester bond with different alkyl chains. The addition of an alkyl group will enhance the lipophilicity of epinephrine (increase log P) and will consequently increase its permeability through the biological membranes (sublingual and buccal tissues in the oral cavity).

Claims5

Dependent claims

A compound formulated as a pharmaceutical composition in a unit dosage form configured for sublingual or buccal administration of a Formula:

wherein R is selected from the group consisting of:
—CHCH2, —CHCHCH3, —CH2—CH2—Cl, —CHCH2I, —CH(Cl)CH2 (Cl), —CH(I)CH2(I), —CH(CH3)CH2(CH3), —CH2C(CH3)3, —CH2CH2CH3, —CH2CI, —CH2I, —CH2F, H, CI, I, F, —CH(CH3)CH(CH3)2, —CH(Cl)CH(Cl)2, —CH(I)CH(I)2, —CH(F)CH(F)2, —CH2CHCH2, —C(Cl)2CH(Cl)2, —C(I)2CH(I)2, —C(Cl)3, C(I)3, —CH2COCH3, —CH2COCl, —CH2CO(I), —CH2OCH3, —CH(I)(CH3), —C(Cl)2(CH3), —CH2CH(CH3)2, —CH2CH(Cl)2, —CH2CH(I)2, —CH2C(Cl)3, —CH2C(I)3, —CH(Cl)2, —CH(I)2, —C(CH3)2CH(CH3)2, —NH—C(CH3) 3, —NH—CH(CH3)2, —NH—CH2CH3, —NH—CH3, —SCH3, —SCH2CH3, —SCH(CH3)2, —SC(CH3)3, —CH2C6H5 and —C6H5 or a pharmaceutically acceptable salt thereof, wherein said compound has a Log P value in the range of about 0.5-6.0 and wherein the compound is formulated in a unit dosage form as a rapidly dissolving film and has a half-life t1/2 range from 1-6 minutes.

Dependencies are inferred from the claim text.

Pharmaceutical formulation for sublingual or buccal delivery of epinephrine or a pro-drug thereof

Life of this patent

Pharmaceutical formulation for sublingual or buccal delivery of epinephrine or a pro-drug thereof

Life of this patent

Abstract

Claims5