Processes for the preparation of multicomponent crystalline forms of active pharmaceutical ingredients using solvent vapour
AssigneeApotex Inc.
InventorsAlexander J. Stirk, Fabio E. S. Souza, Avedis Karadeolian, Allan W. Rey, Fatemeh Mohammadpourmir
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Abstract
The present invention provides solvent-limited processes for the preparation of an existing crystalline solid form of an active pharmaceutical ingredient comprising mixing, in the presence of solvent vapour, of a solid active pharmaceutical ingredient and a pharmaceutically acceptable entity that is either a high-boiling liquid or a solid. Also provided is the use of a standard rotary apparatus, such as a rotary cone dryer, for application of the processes herein.
Claims14
A process for the preparation of an existing crystalline solid form comprising an active pharmaceutical ingredient and a distinct pharmaceutically acceptable entity, wherein the existence of the crystalline solid form has been confirmed prior to conducting the process, the process comprising mixing, in the presence of solvent vapour, of:
- (i) the active pharmaceutical ingredient in solid form;
- and
- (ii) the pharmaceutically acceptable entity, in solid or liquid form,
- wherein the entity has a melting point greater than approximately 30° C. or a boiling point greater than approximately 150° C. and the pharmaceutically acceptable entity and active pharmaceutical ingredient are incorporated in the same crystalline lattice,
- wherein the mixing is conducted in a rotary apparatus by means of rotation of a vessel containing the active pharmaceutical ingredient and the entity about its own axis,
- wherein the rotary apparatus comprises:
- a fixed support structure;
- a vessel rotatably supported by the fixed support structure about an axis and defining a chamber for mixing of the active pharmaceutical ingredient and the entity;
- an aperture in the vessel enabling communication between the chamber and a source of solvent vapour;
- and
- means for rotating the vessel about the axis.
A process for the preparation of an existing crystalline solid form comprising an active pharmaceutical ingredient and a distinct pharmaceutically acceptable entity, wherein the existence of the crystalline solid form has been confirmed prior to conducting the process, the process comprising mixing, in the presence of solvent vapour, of:
- (i) the active pharmaceutical ingredient in solid form;
- and
- (ii) the pharmaceutically acceptable entity, in solid or liquid form,
- wherein the entity has a melting point greater than approximately 30° C. or a boiling point greater than approximately 150° C. and the pharmaceutically acceptable entity and active pharmaceutical ingredient are incorporated in the same crystalline lattice,
- wherein the entity is an acid and the crystalline solid form is a salt,
- wherein the active pharmaceutical ingredient is an amine and the acid has a melting point greater than approximately 30° C., and
- wherein the acid is selected from the group consisting of fumaric acid, maleic acid, L-malic acid, succinic acid, citric acid, L-tartaric acid, oxalic acid, and naphthalene-2-sulfonic acid.
Dependencies are inferred from the claim text.