Merck Sharp + Dohme Corp.

Cerecor, Inc.

Avalo Therapeutics, Inc.

Todd D Nelson

Blake Paterson

Reza Mazhari

James Vornov

Djelila Mezaache

Rachel M Garner

Dennis H Leung

Elizabeth Kwong

Timothy A Rhodes

Blake M Paterson

The disclosed subject matter provides certain polymorphic forms of Compound (I) as well as pharmaceutical compositions comprising Compound (I) or such polymorphic forms, and methods of using or making such compounds and pharmaceutical compositions. It has now been discovered that Compound (I) can exist in multiple crystalline forms (polymorphs). One particular crystalline form, Form II, has been found to be more thermodynamically stable and, thus, likely more suitable for bulk preparation and handling than other polymorphic forms. Efficient and economic methods have been developed to prepare Compound (I) and Form II in high purity on a large scale. In animal studies, Form II has demonstrated safety and efficacy in treating depressive disorders and, when micronized, improved absorption compared to non-micronized Form II.

Compounds, compositions and methods

The disclosed subject matter provides certain polymorphic forms of Compound (I) as well as pharmaceutical compositions comprising Compound (I) or such polymorphic forms, and methods of using or making such compounds and pharmaceutical compositions. It has now been discovered that Compound (I) can exist in multiple crystalline forms (polymorphs). One particular crystalline form, Form II, has been found to be more thermodynamically stable and, thus, likely more suitable for bulk preparation and handling than other polymorphic forms. Efficient and economic methods have been developed to prepare Compound (I) and Form II in high purity on a large scale. In animal studies, Form II has demonstrated safety and efficacy in treating depressive disorders and, when micronized, improved absorption compared to non-micronized Form II. 

Described herein is a process for preparing nano-suspensions, wherein the process comprises: providing an admixture of at least one active pharmaceutical compound, an aqueous dispersion medium, and milling media and applying thereto acoustic energy having a frequency of from about 10 hertz to 1000 hertz and which supplies a linear acceleration of from about 10 G's to about 100 G's (where 'G' is the force of gravity) for a period sufficient to supply a nano-suspension having a Dof less than about 1 micron, preferably less than about 500 nm. Described also are nano-suspensions having novel properties prepared via the inventive process.

Nano-suspension process

Growing community of inventors

Cream Ridge, NJ, United States of America

Todd D Nelson