Use of purified donepezil maleate for preparing pharmaceutically pure amorphous donepezil hydrochloride

A process for preparing donepezil maleate comprising the steps of:

• providing a solution of donepezil base in an organic solvent;
• adding maleic acid and precipitating crude donepezil reaction product as donepezil maleate;
• cooling the reaction product and separating the obtained solid;
• and
• optionally washing the solid with water and a second organic solvent and isolating the product.

A process for crystallizing donepezil maleate comprising the steps of:

• dissolving donepezil maleate in an organic solvent, optionally at reflux conditions;
• cooling and mixing to afford crystals;
• and
• filtering the obtained solid and washing.

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 phases;
• washing the organic phase with water and separating the phases;
• adding equimolar quantity of aqueous hydrochloric acid to the organic phase and separating the phases (donepezil hydrochloride is freely soluble in water);
• optionally adding an inactive pharmaceutical ingredient to the aqueous phase and stirring to dissolution;
• and
• evaporating the water by freeze drying or spray drying.