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 document describes an oral pharmaceutical composition comprising a mixture of at least two distinct types of particles for dabigatran etexilate. A first type of particles comprises dabigatran etexilate in the form of the free base or in the form of a pharmaceutically acceptable salt or polymorph thereof, and the first particle type is free from organic acids and inorganic acids.

A second particle type comprises at least one pharmaceutically acceptable organic acid and is free from dabigatran etexilate. The second particle type containing the pharmaceutically acceptable organic acid is coated with a protective coating layer, so that the second particle type is maintained as a separate coated component from the first particle type. The document describes forms including dabigatran etexilate mesylate and polymorphs Form I and Form II.

The document further describes capsule formulations in which the two particle types are prepared as separate fractions and then combined for oral administration. Preparation embodiments include granulation and coating sequences, including alternative coating order, and embodiments involving extruding/spheronization to form organic-acid pellets followed by protective coating and combination with dabigatran etexilate granules and filling into hard capsules.

Claims Coverage

The independent claims cover three closely related compositions/capsules in which inventive particle-mixture structure is defined by at least two distinct particle types containing (i) dabigatran etexilate that is free from organic and inorganic acids and (ii) pharmaceutically acceptable organic acid particles that are coated with a protective coating layer and are free from dabigatran etexilate. Across the independent claims, the main inventive structure is supplemented by requirements for excipients and, in dependent forms, quantitative composition and capsule dosage ranges.

Across the independent claims, the claims focus on a two-particle-type formulation architecture: one particle type carries dabigatran etexilate and excludes organic/inorganic acids, while the other carries pharmaceutically acceptable organic acid and is protected by a protective coating layer while excluding dabigatran etexilate. Additional coverage includes the presence of pharmaceutically acceptable excipients and, for one claim family, the formulation presented as a capsule.

Stated Advantages

Documented Applications