Browse Prior Art Database

REGORAFENIB FORMULATION

IP.com Disclosure Number: IPCOM000246089D
Publication Date: 2016-May-04
Document File: 6 page(s) / 201K

Publishing Venue

The IP.com Prior Art Database

Abstract

The present disclosure relates to a pharmaceutical formulation comprising regorafenib, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, and optionally one or more pharmaceutically acceptable excipients, and a process for its preparation.

This text was extracted from a Microsoft Word document.
At least one non-text object (such as an image or picture) has been suppressed.
This is the abbreviated version, containing approximately 24% of the total text.

REGORAFENIB FORMULATION

Abstract

The present disclosure relates to a pharmaceutical formulation comprising regorafenib, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, and optionally one or more pharmaceutically acceptable excipients, and a process for its preparation.

Reported herein is a pharmaceutical formulation comprising:

(i)   regorafenib;

(ii)   polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; and

(iii) optionally one or more pharmaceutically acceptable excipients.

The weight ratio of regorafenib to polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer ranges from about 1:1 to about 1:10, preferably from about 1:1 to about 1:4, more preferably from about 1:1 to about 1:3, and most preferably about 1:2.

Reported herein is a process for preparing a pharmaceutical formulation comprising:

(1)   dissolving regorafenib and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer in an organic solvent to prepare a solution;

(2)   blending one or more pharmaceutically acceptable excipients;

(3)   granulating the blend of step (2) with the solution of step (1) to obtain granules;

(4)   optionally compacting and milling the granules of step (3) to obtain milled granules;

(5)   mixing the granules of step (3) or the milled granules of step (4) with one or more pharmaceutically acceptable excipients; and

(6)   formulating the blend of step (5) into a pharmaceutical formulation.

The term “about,” as used herein, refers to any value which lies within the range defined by a variation of up to ±10% of the value.

The term “regorafenib,” as used herein, refers to regorafenib as well its pharmaceutically acceptable salts, polymorphs, prodrugs, solvates, or hydrates.

Polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer has an amphiphilic structure and is capable of solubilizing poorly soluble drugs in aqueous media, which can lead to enhanced bioavailability.  It is commercially available as Soluplus®.

The term “pharmaceutically acceptable excipients,” as used herein, includes any physiologically inert additives that are routinely used in pharmaceutical formulations.  The pharmaceutically acceptable excipients may include, but are not limited to, diluents, disintegrants, lubricants/glidants, binders, and mixtures thereof.

Suitable diluents are selected from the group comprising microcrystalline cellulose, powdered cellulose, dibasic or tribasic calcium phosphate, calcium sulfate, calcium carbonate, lactose monohydrate, lactose anhydrous, sucrose, sorbitol, xylitol, erythritol, kaolin, calcium silicate, maltodextrin, starch, modified starch (e.g., pregelatinized starch, maize starch, and corn starch), and mixtures thereof.

Suitable disintegrants are selected from the group comprising croscarmellose sodium, carboxymethyl cellulose sodium, carboxymethyl cellulose calcium, low-substituted hydroxypropyl cellulose (L-HPC), crospovidone,...