To industrially obtain five kinds of new polymorphic crystal of donepezil hydrochloride with excellent storage stability, useful as a therapeutic agent for various kinds of senile dementia.
The production method for three kinds of new polymorphic crystal (I) to (III) of donepezil hydrochloride shown by the formula is as follows: the compound of the formula is dissolved in ethanol, and hydrochloric acid or hydrogen chloride is then added to the resultant solution followed by addition of isopropyl ether to effect crystallization; although the means for collecting the resultant crystal after filtration depends on the type of crystal, it is general that polymorphic crystal (I) is collected just after deposited; crystal (II) is collected 10-60 (pref. 10-30)min after deposited; while crystal (III) is collected one hour or longer (pref. 24h or longer) after deposited. The other two kinds of polymorphic crystal (IV) and (V) are obtained by humidifying the polymorphic crystal (II) and by heating the polymorphic crystal (IV) respectively.
WATANABE HIDEAKI
KAJIMA TAKASHI
ISHIHAMA YASUSHI
OOTSUKA AKIYO
TANAKA TOMOHIDE
NARABE YUKIO
EISAI KAGAKU KK