	US 7,592,459 B2
	Use of purified donepezil maleate for preparing pharmaceutically pure amorphous donepezil hydrochloride
Oded Arad, Rechovot (Israel); Lior Zelikovitch, Mazkeret Batia (Israel); Mohammed Alnabari, Hura (Israel); Michael Brand, RaAnana (Israel); Irina Gribun, Bat-Yam (Israel); Ada Salman, Ramat-Gan (Israel); Meital Shiffer, Tel Aviv (Israel); Moty Shookrun, Petach-Tikva (Israel); Orna Kurlat, Beer-Sheba (Israel); Moshe Bentolila, Moshav Tkuma (Israel); and Joseph Kaspi, Givatayim (Israel)
Assigned to Chemagis Ltd., Bnei-Brak (Israel)
Filed on Sep. 27, 2005, as Appl. No. 11/235,106.
Claims priority of provisional application 60/613707, filed on Sep. 29, 2004.
Prior Publication US 2006/0069125 A1, Mar. 30, 2006
Int. Cl. C07D 211/02 (2006.01)

U.S. Cl. 546—206 [546/205; 514/319]

7 Claims

1. A process for converting donepezil maleate to amorphous donepezil hydrochloride of pharmaceutical purity, comprising the steps of:

suspending pure donepezil maleate in a mixture of an organic solvent and water;

adding aqueous inorganic base;

extracting and separating the aqueous phase from the organic phase;

washing the organic phase with water and separating the aqueous phase from the organic phase;

adding equimolar quantity of aqueous hydrochloric acid to the organic phase and separating the aqueous phase from the organic phase;

optionally adding an inactive pharmaceutical ingredient to the aqueous phase and stirring to dissolution; and

evaporating the water directly from the aqueous extraction phase by freeze drying or spray drying, to produce pharmaceutically pure amorphous donepezil hydrochloride.