or 2,3-Dihydro-5,6-dimethoxy-2-[[1-(phenylmethyl)-4-piperidinyl]methyl]-1H-inden-1-one hydrochloride is useful for prevention and treatment of alzheimer disease. The therapeutic uses of donepezil hydrochloride and related compounds are disclosed in EP 296560. Amorphous form of donepezil hydrochloride is mentioned in U.S. Pat. No. 6,140,321.

We have discovered a simple novel process for the preparation of amorphous form of donepezil hydrochloride.

The object of the present invention is to provide a novel process for the preparation of the amorphous form of donepezil hydrochloride.

›DETAILED DESCRIPTION OF THE INVENTION

The amorphous donepezil hydrochloride is characterized by having broad x-ray diffraction spectrum as in FIG. 1 .

One aspect of the present invention provides a process for the preparation of amorphous donepezil hydrochloride. Amorphous donepezil hydrochloride is prepared by dissolving donepezil hydrochloride in a mixture comprising an alcoholic solvent and a chlorinated solvent; and removing the solvents from the solution. The solvents can be removed by techniques such as vacuum drying, lyophilization, distillation under vacuum, freeze drying, spray drying, etc. The alcoholic solvent is selected from the group consisting of methanol, ethanol, isopropyl alcohol, tert-butyl alcohol and n-butyl alcohol. Methanol is a preferred solvent. The suitable chlorinated solvents are chloroform, methylene dichloride, carbontetrachloride and ethylene dichloride. Methylene dichloride and chloroform are preferred solvents.

›BRIEF DESCRIPTION OF THE DRAWING

FIG. 1 is a x-ray powder diffraction spectrum of amorphous donepezil hydrochloride.

x-Ray powder diffraction spectrum was measured on a Siemens D5000 x-ray powder diffractometer having a copper-Kα radiation.

The following examples further illustrate the invention.

›Examples4

›EXAMPLE 1

Donepezil hydrochloride (10 gm, obtained by the process described in example 4 of EP 296560) is dissolved in the mixture of methanol (50 ml) and chloroform (50 ml). The solution is subjected to vacuum drying at about 40° C. for 10 hours to give 9.1 gm of amorphous donepezil hydrochloride.

›EXAMPLE 2

Example 1 is repeated by subjecting the solution to spray drying instead of vacuum drying using nitrogen gas to give amorphous donepezil hydrochloride.

›EXAMPLE 3

Crystalline donepezil hydrochloride (10 gm) is dissolved in the mixure of ethanol (60 ml) and chloroform (50 ml). The solution is subjected to vacuum drying at about 45° C. for 9 hours to give 9.2 gm of amorphous donepezil hydrochloride.

›EXAMPLE 4

Example 3 is repeated by subjecting the solution to spray drying using nitrogen gas instead of vacuum drying to give amorphous donepezil hydrochloride.

Claims as granted

7 claims

Classifications

3 codes

IPC · International Patent Classification

Section C — Chemistry; metallurgy

C07D211/32

USPC · US Patent Classification

546/205546/206

Claim changes

Soon

Coming soonHow the claims changed between publication and grant

See which claims were amended, added or cancelled during examination, with every added and removed word marked.

AmendedAddedCancelledUnchanged

The published claims of this application are not paired with the granted ones in what we hold.

File wrapper

⤢ drag to zoom

USPTOApplicanthover for detail · click to open

Pendency

7.4 y

2,687 days filing → grant

Office actions

non-final + final

Responses

1 RCE

Interviews

examiner interview summaries

Examiner

Celia Chang

art unit 1625 · TC 1600

Law firm

Law firm · Log in to unlock

Citations: 15 back · 1 forward

See the full prosecution history — every USPTO and applicant action on this file, in order.

Documents

Log in to open the documents of this file: the application as filed, every office action and response, the notice of allowance.

Chain of title

⤢ drag to zoom

Titlehover for detail · click to open

See the full assignment history — every owner this patent has passed through, with recordation dates and reel/frame numbers.