Methods of producing anamorelin hydrochloride having controlled chloride content
AssigneesOno Pharmaceutical Co., Ltd., Helsinn Healthcare SA
InventorsShin-itsu Kuwabe, Takehiko Yanagimachi, Hideyuki Yoshiyama, Seemon Pines, Eleanor de Groot, Silvina Garcia Rubio, Peter Manini
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Abstract
The present invention relates to particulate forms of anamorelin monohydrochloride or a composition comprising anamorelin monohydrochloride having controlled chloride content, preferably isolated in an amorphous and/or fine particulate state, processes for making the particulate forms, and pharmaceutical compositions comprising the particulate forms.
Claims29
A process for preparing amorphous anamorelin monohydrochloride comprising:
- a) dissolving anamorelin free base in an organic solvent to form a solution;
- b) mixing said solution with water and hydrochloric acid for a time sufficient to:
- i) react said anamorelin free base with said hydrochloric acid, and
- ii) form an organic phase and an aqueous phase;
- c) separating the aqueous phase from the organic phase;
- and
- d) isolating said amorphous anamorelin monohydrochloride from said aqueous phase.
A process for preparing amorphous anamorelin monohydrochloride comprising:
- a) dissolving anamorelin free base in an organic solvent to form a solution;
- b) mixing said solution with water and hydrochloric acid for a time sufficient to:
- i) react said anamorelin free base with said hydrochloric acid, and
- ii) form an organic phase and an aqueous phase;
- c) separating the aqueous phase from the organic phase;
- d) removing residual organic solvent from said aqueous phase via distillation;
- and
- e) isolating said amorphous anamorelin monohydrochloride from said aqueous phase;
- wherein (i) anamorelin free base is more soluble in the organic solvent than in water, and (ii) amorphous anamorelin monohydrochloride is more soluble in water than the organic solvent.
A process for preparing amorphous anamorelin monohydrochloride comprising:
- a) dissolving anamorelin free base in isopropyl acetate to form a solution;
- b) mixing said solution with water and hydrochloric acid for a time sufficient to:
- i) react said anamorelin free base with said hydrochloric acid, and
- ii) form an organic phase and an aqueous phase;
- c) separating the aqueous phase from the organic phase;
- d) removing residual isopropyl acetate from said aqueous phase via azeotropic distillation;
- and
- e) isolating said amorphous anamorelin monohydrochloride from said aqueous phase.
Dependencies are inferred from the claim text.