only one example of the prior art deals with the problem of avoiding a conversion of polymorphic forms of donepezil hydrochloride during processing into the desired solid composition or during prolonged storage . according to the cited document it is only possible to prevent an undesired conversion of the specific polymorphic form of donepezil hydrochloride by controlling a content of water in between of 3 and 10 % by weight ( determined by karl - fischer ). within this invention it has been surprisingly found that prevention of the undesired conversion of the specific polymorphic form of donepezil hydrochloride and therefore the desired stability of the final pharmaceutical composition can also be achieved with a content of water of less than 3 % by weight , preferably less than 2 % by weight , more preferably less than 1 . 8 % by weight , even more preferably less than 1 . 6 % by weight ( determined by karl - fischer ). according to the invention we provide pharmaceutical composition comprising donepezil or a pharmaceutically acceptable salt ( preferably hydrochloride ) thereof in the form of a hydrate , the pharmaceutical composition having a content of water of less than 3 % by weight ( determined by karl - fischer ) an object of the present invention is to provide a stable pharmaceutical composition of donepezil hydrochloride preferably monohydrate in which specific polymorphic form of donepezil hydrochloride is stable and does not convert to other polymorphic forms ( e . g . form ii or form iii ) during formulation . donepezil hydrochloride within the composition is preferably of form i . it is a further object of the present invention to provide the given pharmaceutical composition in one of following forms ; tablet ( optionally with applied film coating ), a capsule , pellets or in form of mini tablets filled in capsule . the preferred form is that of a tablet and more preferably in form of a film coated tablet . tablet can be of round or oval biconvex shape with optionally scored or debossed sides if desired . the preferred shape is round . it is a further object of the present invention to provide a tablet formulation of the given composition comprising donepezil hydrochloride with a content of water of less than 3 % by weight . it is a further object of the present invention to provide a tablet formulation of donepezil hydrochloride in which the tablet may readily be manufactured and does not demonstrate manufacturing problems such as capping , lamination , segregation ( inhomogeneity ) and poor flow characteristics . desired formulation of the given composition can be obtained by commonly used technologies : dry granulation , wet granulation and direct compression . preferably it is done by means of direct compression . according to the direct compression method a manufacturing process includes following steps : 1 . homogenization of active substance and excipients to obtain tabletting blend 2 . compression of tabletting blend into tablet cores and 3 . optionally , film coating of tablet cores a procedure of obtaining a tabletting blend is performed in a specific way that gives adequate quality of the final product in terms of homogeneity and uniformity of tabletting blend by mixing under the specified process parameters . the tabletting blend is afterwards processed on rotary tablet press under set conditions in order to obtain tablet cores of specified characteristics ( e . g . appropriate hardness that ensures low friability of tablet cores and enables satisfactory film coating ). direct compression method has the advantage of employing the least amount of operational manipulation , the key running powder requirements ( blend homogeneity , consistent bulk density , flow and compressibility ) must be met by the dry blend of active agent with excipients as there is no chemical or physical modification before tabletting . produced tablet cores can optionally be subjected to a film coating process with conventional materials used for film coating ( as described in pharmaceutical coating technology , 1995 .). film coating is a process wherein tablet cores are tumbled in coating pan while heating and applying film coating material are performed . therefore appropriate friability is essential for maintaining integrity of tablets and thereby acceptable appearance of final product . according to the invention we provide a pharmaceutical composition comprising donepezil or a pharmaceutically acceptable salt ( preferably hydrochloride ) thereof in the form of a hydrate , the pharmaceutical composition having a content of water of less than 3 % by weight ( determined by karl - fischer ). the filler , which can be selected from one or more of the following ; lactose monohydrate , lactose anhydrate , starch , sugar or sugar alcohols ( such as glucose , sucrose , sorbitol , mannitol ), celluloses ( in powder forms of different types ( e . g . microcrystalline cellulose )), and dicalcium phosphate dihydrate . the lactose may be in the form of lactose monohydrate or lactose anhydrate , but will preferably be lactose anhydrate . the lactose may be crystalline or amorphous . suitably the lactose may be spray - dried ( e . g . spray dried lactose anhydrate , e . g . pharmatose ™ dcl 22 ). starch may for example be corn starch ( e . g . unmodified corn starch or alternatively pre - gelatinised corn starch ). the starch may also convey some disintegrant properties to the formulation . the total amount of filler present in the final composition is 50 to 92 % by weight , preferably 65 to 90 % by weight . the binder , which can be selected from one or more of the following ; hydroxypropyl cellulose , hydroxypropylmethyl cellulose or other cellulose ethers , vinylpyrrolidone containing polymers . preferably it will be hydroxypropyl cellulose . suitably the cellulose will be present in the final formulation at a concentration of 1 to 10 % by weight , preferably 2 to 5 % by weight , more preferably 3 to 4 % by weight . the vinylpyrrolidone containing polymer may for example be polyvinylpyrrolidone alone or a mixture of polyvinylpyrrolidone and a co - polymer of vinylpyrrolidone and vinyl acetate or a co - polymer of vinylpyrrolidone and vinyl acetate alone . the binder and the filler combined are present in the final formulation at a concentration of 50 to 97 %, preferably 70 to 95 % by weight , more preferably 80 to 93 % by weight . the antiadherent which can be selected from one or more of the following ; colloidal silicon dioxide ( e . g . aerosil ™ 200 ) or talc . preferably the antiadherent is colloidal silicon dioxide . antiadherent is added to the composition in order to improve the flow and packing properties of the composition . antiadherent will be included in an amount of 0 . 1 to 5 % by weight , preferably 0 . 5 to 1 . 5 % by weight . the disintegrant which can be selected from one or more of the following ; crospovidone ( cross linked polyvinylpyrrollidone ), sodium starch glycolate , croscarmellose sodium , powdered cellulose , microcrystalline cellulose or carboxymethylcellulose calcium . preferably disintegrant is sodium starch glycolate . disintegrant is added to the composition to enhance the disintegrating properties of the composition and thereby to accelerate dissolution . disintegrant will be included in an amount of 1 to 10 % by weight , preferably 3 to 8 % by weight , more preferably 5 to 7 % by weight . the lubricant which can be selected from one or more of the following ; stearic acid , metal salt stearates ( magnesium stearate , zinc stearate and calcium stearate ), sodium stearyl fumarate , sodium lauryl sulphate , sodium benzoate , glyceryl behenate , glyceryl monostearate , glyceryl palmitostearate , polyethylene glycol , hydrogenated vegetable oil and talc . preferably lubricant is magnesium stearate . lubricant will be included in an amount of 0 . 1 to 5 % by weight preferably 0 . 5 to 1 . 5 % by weight . the desired stability of polymorphic form within the described composition , with the content of water in total amount of less than 3 % by weight , is achieved as shown in fig1 . fig1 shows the results of the xrpd analysis performed on samples of the final product of the described composition . samples subjected to analysis for which results are shown in fig1 : 1 . ref . code blacto — calculated xrpd pattern of anhydro lactose ( β lactose ). data taken from cambridge structural database version 5 . 27 , k . hirotsu , a . shimada bull . chem . soc . jpn . 47 ( 1974 ) 1872 . 2 . donepezil hydrochloride form i 3 . final formulation ( film tablets ) of donepezil : don 48 / 10f donepezil hydrochloride was mixed with starch , lactose anhydrous , hydroxypropyl cellulose , sodium starch glycolate and colloidal silicon dioxide and homogenized for 25 minutes . magnesium stearate , screened through a 0 . 6 mm sieve , was added to the core component above . the final blend was homogenised for additional 5 minutes and then compressed into tablets . the tablets were coated with aqueous suspension of lactose monohydrate , hydroxypropylmethyl cellulose , polyethylene glycol , titanium dioxide and iron oxide yellow donepezil hydrochloride was homogenised with lactose anhydrous , hydroxypropyl cellulose , sodium starch glycolate and colloidal silicon dioxide for 20 minutes . sodium stearyl fumarate , screened through a 0 . 6 mm sieve , was added to the core component above . the final blend was homogenised for additional 5 minutes and then compressed into tablets . the tablets were filled in the capsules . donepezil hydrochloride and hydroxypropyl cellulose were homogenized for 10 minutes and compressed into tablets . the tablets were afterwards milled and sieved through suitable sieve and added to the other substances , except magnesium stearate . magnesium stearate , screened through a 0 . 6 mm sieve , was added to the core component above . the final blend was homogenised for additional 5 minutes and then compressed into tablets . the tablets were coated with aqueous suspension of lactose monohydrate , hydroxypropylmethyl cellulose , polyethylene glycole , titanium dioxide and iron oxide yellow
the present invention relates to a pharmaceutical composition comprising 2 , 3 - dihydro - 5 , 6 - dimethoxy - 2 -- 4 - piperidinyl ] methyl ]- 1h - inden - 1 - one , herein after referred to as donepezil , or a pharmaceutically acceptable salt thereof , for treating of alzheimer &# 39 ; s disease and senile dementia . the present invention also relates to a manufacturing process for the preparation of donepezil tablets containing and retaining polymorphic form i of donepezil hydrochloride . this composition also discloses the use of the excipients that ensure adequate flowability of a dry blend as well as required content uniformity and drug release rate of the final product .