LONG-ACTIVE DRUG FORMULATIONS COMPRISING GALANTHAMINE FOR TREATMENT OF ALZHEIMER'S DISEASE

COMPOSITIONS PHARMACEUTIQUES A ACTION PROLONGEE CONTENANT DE LA GALANTHAMINE POUR LE TRAITEMENT DE LA MALADIE D'ALZHEIMER

English Abstract

A B S T R A C T
Long acting Galanthamine formulation is prepared by
coating particles of drug with polyvinyl pyrrolidone, sizing
the particles and incorporating them into a capsule or tablet.

Claims

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE PROPERTY OR PRIVILEGE
? CLAIMED ARE DEFINED AS FOLLOWS:
1. A sustained release formulation for oral
administration in the form of a tablet or capsule for
treatment of Alzheimer's disease and related dementias
comprising particles of galanthamine or a pharmaceutically
acceptable salt thereof, said particles being coated with a
pharmaceutically acceptable coating agent that is soluble in
the intestinal tract, the thickness of the coatings varying
between individual particles, a plurality of said particles
having various coating thickness chosen so as to result, after
administration, in release of the drug from its coated
particles at different times.
2. A sustained release formulation as claimed in
claim 1 wherein said particles comprise galanthamine
hydrobromide.
3. A sustained release formulation as claimed in
claim 1 wherein said coating material is polyvinyl
pyrrolidone.
4. A sustained release formulation as claimed in
claim 1 containing 25 to 250 mg of active compound.
- 3 -

Description

~32~32
The present invention relates to long-acting
formul~tions for treatment of Alzheimer's disease and related
dementias,
United States Patent No. 4,663,318 ~Davis issued
May 51 l9B7) describes the use of galanthamine and its salts
for treatment of Alzheimer's disease and related dementias.
The possibility o~ using a long-acting fo~mulation o~ the drug
is suggested therein.
Ac~ording to the present invention, there is
provided a sustained release formulation in ~he form of a
tablet o~ capsule for oral administration for treatment of
Alzheimer's disease and related dementias comprising particles
of galanthamine or a pharmaceutically acceptable salt thereof.
A pr~ferred compound of the above ~ormula is
, galanthamine hydrobromide.
,~, Suikable pharmaceutically acceptable coating agents ~-:
include polyvinyl pyrrolidone.
A par~icularly useful method for producing
I formulations o~ the present invention i~ to coat the drug
;~ substance with polyvinyl pyrrolidone alcohol 601ution to form
:~ granules. These granules are the~p~s~sed thru a sieve machine
to obtain various ~izes o~ granules. A dete~mlned amount of
each of dif~erant ~ize granules are mixed with excipient such
~ : as hydroxypropyl methyI c211ulose, ethyl cellulose, starch,
¦ ~ilicon dioxide, and with a lubricant such as magnesium
i tearate or polyethylene glycol to form a tablet or to be
1~ ~ incorporated into a capsule.
l~ The final drug preparation i6 tested for dissolution . :
.1 pro~ile in addition to the general testing requirements. A :
useful dis~olution profile for a ~ustained release preparation
according to ~h~ presen~ invention is:
, ~ .
Activ~ drug 1-2 hours 10-20%
~ dissolved 2-4 hours 20-40
:1 in ga~tric ~-8 hour~ 40-80% -
~ uiae 12 hours balance ~
~!
!

~32~3~
Typically the sizing of the particles incorporated
i~to a table or capsule will be chosen so as to produce a
sustained release over a four to twelve hour period, for
example, over a eight hour period.
Typically capsules or tablets according to the
present invention contain a quarter to a half of the typical
daily dose of drug, although dosage units outside this range
are also possible. Such daily doses are normally or 10 to
2000 mg per day, more typically 100 to 600 mg per day.
Typically, therefore, tablets or capsules comprise 25 to
250 mg o~ active compound.
,f~ '"
.~
,~ :
.j .
',