Pharmaceutical compositions containing a dgat1 inhibitor

Abstract

The present invention relates to a pharmaceutical composition comprisinga) a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof,b) one or more, e.g. 1, 2 or 3, surfactants with lubricant properties;c) one or more, e.g. 1, 2 or 3, dry binders with disintegrant properties;d) one or more, e.g. 1, 2 or 3, fillers, ande) one or more, e.g. 1, 2 or 3, disintegrants.

Description

FIELD OF THE INVENTION[0001]The present invention relates to pharmaceutical compositions comprising (4-{4-[5-(6-trifluoromethyl-pyridin-3-ylamino)-pyridin-2-yl]-phenyl}-cyclohexyl)-acetic acid, or a pharmaceutically acceptable salt thereof, e.g. the sodium salt thereof, as the active ingredient in a suitable carrier. The present invention also relates to the processes for their preparation and to their use as medicaments.[0002]As disclosed in WO 2007 / 126957, a genus of compounds as DGAT1-inhibitors, Including, at Example 5-1, the compound (4-{4-[5-(6-trifluoromethyl-pyridin-3-ylamino)-pyridin-2-yl]-phenyl}-cyclohexyl)-acetic acid, having the structural formula (I):and its sodium saltmay be employed in the treatment of a condition or a disorder such as inflammatory conditions, obesity, diabetes and related metabolic disorders.[0003]Administration of such pharmaceutical agents via the oral route is preferred to parenteral administration because it allows self-administration by patient...

AI Technical Summary

Benefits of technology

[0014]The formulations of the present invention are also achievable via a robust manufacturing process; which gives good flowability, compactibility, and which minimizes sticking problems and capping of tabletting mixtures on the rotary press. The process and the formulations are amenable to scale-up, with a reproducible performance.

[0015]Accordingly the present invention provides a pharmaceutical composition comprising

[0016]a) a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof,

[0017]b) one or more, e.g. 1, 2 or 3, surfactants with lubricant properties;

[0018]c) one or more, e.g. 1, 2 or 3, dry binders with disintegrant properties;

[0019]d) one or more, e.g. 1, 2 or 3, fillers, and

[0020]e) one or more, e.g. 1, 2 or 3, disintegrants.

Problems solved by technology

However, the compound of formula (I), or a pharmaceutically acceptable salt thereof, in particular the sodium salt thereof, is a drug substance which is difficult to formulate due to its physicochemical properties.

It is also plate like, very fluffy, and sticky in nature.

It also exhibits poor flow characteristics.

These characteristics of the drug substance make it particularly problematic to develop formulations comprising the compound of formula (II) which would be amenable to withstanding the compression forces required for a tablet form of the pharmaceutical composition with an adequate hardness window.

During the course of development, it has been found to be difficult to achieve such a formulation.

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