Oral pharmaceutical compositions of dabigatran etexilate

Inventors

Pilgaonkar, Pratibha S. • Rustomjee, Maharukh T. • Gandhi, Anilkumar S.

Assignees

Breckenridge Pharmaceutical Inc

Abstract

Compositions comprising a mixture of at least two types of particles wherein a) the first type of particles comprise dabigatran etexilate in the form of the free base or in the form of pharmaceutically acceptable salts, polymorphs, solvates or hydrates thereof; and b) the second type of particles comprise at least one pharmaceutically acceptable organic acid, use of said compositions in the reduction of the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation and/or in the prevention of venous thromboembolic events in adult patients who have undergone elective total hip replacement surgery or total knee replacement surgery and processes for the preparation of said compositions.

Core Innovation

The invention relates to oral dabigatran etexilate formulations in which a composition includes a mixture of at least two distinct types of particles. A first type of particles comprises dabigatran etexilate in the form of the free base or a pharmaceutically acceptable salt or polymorph, and this first particle type is free from organic acids and inorganic acids. A second type of particles comprises at least one pharmaceutically acceptable organic acid, and this second particle type is coated with a protective coating layer while being free from dabigatran etexilate.

The formulation provides particle-type separation between dabigatran etexilate and the pharmaceutically acceptable organic acid, including tartaric acid in some embodiments. The described particle mixture is implemented in an oral unit-dose form such as capsules, including capsule preparations.

The invention is further characterized by compositional ranges and dissolution-related performance, including mixtures where dabigatran etexilate is present in a range from about 0.01 to 90 wt% and the organic acid is present in a range from about 2 to 95 wt%. The described comparison indicates faster early-time dissolution versus single-particle-type formulations containing components together.

Claims Coverage

The document provides three independent claims directed to an oral dabigatran etexilate particle-mixture composition and its use in reducing stroke and systemic embolism risk in non-valvular atrial fibrillation and in treating venous thromboembolic events after elective total hip replacement or elective total knee replacement. Across the independent claims, four core inventive features are repeatedly required.

Overall, the claim set centers on administering an oral composition that separates dabigatran etexilate from pharmaceutically acceptable organic acids at the level of distinct particle types, with the organic-acid particles protected by a protective coating layer and the dabigatran-containing particles being free of the specified acids. The claims further include a specialized capsule embodiment in which tartaric acid is specifically the organic acid component and is absent from the dabigatran-containing particle type.

Stated Advantages

Documented Applications