Oral amphetamine composition

Inventors

Venkatesh, Gopi M. • Schilling, Michelle

Assignees

Adare Pharma Solutions Inc

Interested in licensing this patent?

MTEC can help explore whether this patent might be available for licensing for your application.

Publication Number

US-10441554-B2

Patent

Publication Date

2019-10-15

Expiration Date


Abstract

In various embodiments, the present invention is directed to oral pharmaceutical compositions. For example, in some embodiments, the present invention is directed to taste-masked compositions. In some embodiments, the taste masked compositions comprise a highly water soluble drug such as amphetamine, e.g., in the form of a salt such as amphetamine sulfate. In various embodiments, the present invention is directed to taste-masked, orally disintegrating compositions.

Core Innovation

The invention relates to an orally disintegrating pharmaceutical composition that includes taste-masked drug-containing particles containing racemic amphetamine, or a pharmaceutically acceptable salt or ester thereof. The composition is designed to form an orally dispersing, non-gritty viscous suspension in saliva and to reduce bitterness and aftertaste.

Taste masking is achieved by a two-stage membrane system on the drug-containing core particles. A first taste-masking membrane comprises ethylcellulose and excludes pharmaceutically acceptable gastrosoluble polymers, and a second taste-masking membrane comprises ethylcellulose and aminoalkyl methacrylate copolymer at a 50/50 weight ratio, where the second membrane is disposed on the first membrane.

The composition further includes a disintegrant and a sugar alcohol or saccharide, where the drug-containing particles are combined with rapidly dispersing microgranules. The membrane system remains intact in the mouth but dissolves under gastric conditions to enable release comparable to EVEKEO®, with performance framed using pharmacokinetic acceptance windows for AUCinf, Cmax, and Tmax relative to target values.

Claims Coverage

The independent claim covers a defined orally disintegrating pharmaceutical composition with a specific two-layer ethylcellulose-based taste-masking membrane on racemic amphetamine core particles, along with defined formulation components and pharmacokinetic acceptance ranges tied to a 30 mg racemic amphetamine sulfate dose-equivalent.

Two-stage ethylcellulose taste-masking membranes

A first taste-masking membrane comprising ethylcellulose excluding pharmaceutically acceptable gastrosoluble polymers, and a second taste-masking membrane comprising ethylcellulose and aminoalkyl methacrylate copolymer at a 50/50 weight ratio, disposed on the first membrane.

Racemic amphetamine drug-containing core particles with excipient

Drug-containing core particles comprising a therapeutically effective amount of racemic amphetamine, or a pharmaceutically acceptable salt or ester thereof, and at least one excipient.

Orally disintegrating composition including disintegrant and sugar alcohol or saccharide

The orally disintegrating pharmaceutical composition comprises a disintegrant and a sugar alcohol or saccharide, or mixture thereof.

Pharmacokinetic acceptance windows tied to 30 mg dose-equivalent

Wherein if the orally disintegrating pharmaceutical composition comprises 30 mg of racemic amphetamine sulfate, after administration the composition provides one or more of AUCinf ranging from about 80% to about 125% of about 400-600 hr*ng/mL, Cmax ranging from about 80% to about 125% of about 25-35 ng/mL, or Tmax ranging from about 80% to about 125% of about 2-4 hrs.

Overall, the claim coverage is directed to a taste-masked orally disintegrating composition using a two-layer ethylcellulose membrane system on racemic amphetamine core particles, formulated with a disintegrant and sugar alcohol or saccharide, and meeting specified pharmacokinetic exposure windows for a 30 mg racemic amphetamine sulfate-equivalent dose.

Stated Advantages

Rapid disintegration in saliva to form a smooth, non-gritty viscous suspension with minimal aftertaste.

Reduced bitterness and aftertaste.

Enables release comparable to EVEKEO®.

Provides specified AUCinf, Cmax, and/or Tmax within defined acceptance windows.

Documented Applications

An orally disintegrating pharmaceutical composition for racemic amphetamine sulfate intended to provide rapid oral disintegration and taste-masked delivery with pharmacokinetic performance comparable to a reference listed drug (EVEKEO®).

JOIN OUR MAILING LIST

Stay Connected with MTEC

Keep up with active and upcoming solicitations, MTEC news and other valuable information.