FIELD OF THE INVENTION
The present invention relates to compressible. free flowing granulate and process for preparing the same.
The present invention also relates to free flowing compressible granulate which contain xylitol along with a pharmaceutically acceptable binder, optionally with one or more other pharmaceutically acceptable excipient(s).
The granulate composition of the present invention is particularly suitable for use in the manufacture of solid dosage forms by a dry process such as by direct compression method.
The granulate of the present invention have a pleasant taste and are also suitable for the preparation of taste-masked compositions.
The present invention further relates to process for the preparation of free flowing compressible granulate containing xylitol.
The present invention also relates to method of using the free flowing compressible granulate for the manufacture of solid dosage forms.
The compressible free flowing xylitol granulate of the present invention is useful in the field of food products, food supplements, neutraceuticals and pharmaceuticals.
BACKGROUND OF THE INVENTION
The most commonly used sweetener for food and pharmaceutical contexts is sucrose. Sucrose is used for its well-known sweetening properties and also for bulking purposes. Although a wide variety of alternate sweeteners are available, sucrose is generally considered to be the optimum sweetener with regard to taste profile and technological properties. However, . sucrose has been implicated as a contributory factor in many diseases including hypertension, coronary heart disease, arterial sclerosis and dental caries. These health concerns have led health care professionals to analyze the effects of sucrose and its prominent role in the diet.

Perhaps the most significant, well-documented effect of sucrose is its contribution to tooth decay. The mouth contains a number of bacterial strains which ferment common dietary carbohydrates such as sucrose. This fermentation generates acid as an end product which lowers the pH in the mouth; the lowered pH leads to a demineralization of tooth enamel and finally to the formation of dental lesions or caries.
One approach to fighting dental caries is to reduce or eliminate the amount of fermentable carbohydrates such as sucrose in pharmaceutical or food product's. The replacement of fermentable carbohydrates by sugar substitutes which cannot be fermented, or are less easily fermented by S. mutans and other bacteria has been shown to decrease the development of dental caries.
Xylitol has been used as a sugar substitute in certain contexts (e.g. chewing gum: U.S. Pat. No. 4,514,422 (Yang) and 3,422,184 (Patel)) with practical and commercial success. The use of xylitol is attractive because of its taste and technological advantages. Xylitol is a naturally occurring five carbon sugar alcohol which has the same sweetness as sugar and a caloric content which is less than that of sugar. Xylitol is found in small amounts in many fruits and vegetables and is produced in the human body during normal metabolism. Xylitol is particularly attractive because of its known metabolic, dental and technical characteristics.
From a metabolic perspective, xylitol is metabolized largely independent of insulin, so it can be safely consumed by non-insulin dependent diabetics. Further, xylitol has been shown to delay gastric emptying and to possibly suppress food intake which means it may have an important role in weight reducing diets.
A significant advantage of xylitol is that it is not fermented by S. mutans and other bacteria found in the mouth and, therefore, does not produce acids which, as described herein, contribute to the formation of dental caries.
Xylitol also has significant technological advantages, particularly with respect to taste profile. Xylitol produces a pleasant cooling effect in the mouth when consumed in the crystalline state. The energy required to dissolve one gram of xylitol is 34.6 calories, the highest known value for sugars and sugar alcohols; this produces a physical cooling effect which is desirable

in many contexts. Xylitol is as sweet as sugar and does not typically manifest unpleasant after tastes.
Other polyols, such as sorbitol, mannitol, lactitol and others have also been substituted for sucrose in a variety of contexts. All of these polyols have certain advantages such as non-cariogenicity over sucrose. However, none of the other polyols have been demonstrated to have a cariostatic effect.
Sweetness in pharmaceutical tablets fulfills the purpose of making the product more pleasant to eat and to mask any unpleasant taste of the active ingredient(s). Today, many pharmaceutical tablets are sweetened with sucrose, lactose and other fermentable carbohydrates which are also used as diluents. Replacing sucrose and other fermentable carbohydrates with xylitol in those applications which must be sweetened would eliminate the use of cariogenic formulations in medicaments such as throat lozenges, cough tablets, vitamins, chewable tablets and others, and also takes advantage of the other attributes of xylitol discussed above, such as its noted cooling effect and metabolic characteristics. In food contexts, tablets are usually sucked or chewed by the user and are often used as breath mints. Sucrose is the sweetener of choice in these contexts and has bulking properties as well. Replacing sucrose with xylitol would enable tablets to exploit the unique advantages of xylitol, particularly its anti-caries properties, and its pronounced cooling effect.
The cariostatic effect of xylitol is particularly important because clinical studies have shown that it is not the quantity of sucrose (or other acid producing substances such as maltose, lactose and dextrose), but the frequency of sucrose intake that is critical for caries development. Many pharmaceutical and food tablets are designed to be and are consumed at frequent and/or regular intervals throughout the day. For this reason, some dental researchers have suggested switching from sucrose, maltose, lactose, dextrose to a non-acid producing sweetener such as xylitol in pharmaceutical and food contexts.
Xylitol is not considered to be directly compressible, i.e. crystalline xylitol cannot be compressed into tablets of sufficient hardness and low friability. Xylitol is highly moisture-sensitive and has a low melting point; thus it is quite difficult to granulate it and further compress into a tablet. The problem which is commonly present is the fact that xylitol granules have a tendency to adhere to each other so as to subsequently form loaf. If such

xylitol granules are used to make tablets, then such tablets have poor hardness, are unstable, stick easily to each other and have a poor appearance.
Xylitol has also been admixed with other, polyols to form a mixture which is then compressed. U.K. Patent No. 1,526,020 discloses a method for the production of compressed tablets wherein xylitol is dry blended with another polyol (e.g. sorbitol, mannitol, maltitol) so that the xylitol is present in about 10-90% by weight in the final product. However, the use of a xylitol/additional polyol blend can create, disadvantages. The use of crystalline xylitol produces tablets which are too coarse in many contexts. The use of milled xylitol (less than 200 micron average particle size) produces a dry blended product (with sorbitol, for example) wherein flowability of the blend is extremely poor. Tableting machinery equipped with a force feeder is required. Because this is not a desired characteristic, use of milled xylitol in conjunction with another polyol is not a viable commercial alternative. A granulated form of xylitol would be much preferred.
Finnish Patent Application No. 880892 discloses the use of a granulate which comprises xylitol in the range of about 94% to about 98% by weight and another pharmaceutical^ acceptable-polyol which serves as the binder in the range of about 1-5% by weight. However such granulate need to be prepared under controlled conditions to prevent attack by atmospheric moisture.
Granulation is a process carried out today by various methods including fluidized bed techniques, centrifugal fluidizing, compacting and vacuum techniques. Granulation requires the use of a "binder" which assists the particles to be granulated for granule formation, and the so obtained granules have free flowing properties. Binders which are often used include starch, gelatin, sugars such as sucrose, dextrose, and lactose, natural and synthetic gums, microcrystalline cellulose and others. These binders are not particularly acceptable for use with xylitol because they may impair or eliminate the taste, cariostatic, metabolic and other properties of xylitol which may make it unattractive for preparation of tablets for pharmaceutical use. Some binders, including gum arabic, if utilized as a binder for xylitol, will reduce the perceived cooling effect of xylitol created by xylitol's significant negative heat of solution. Other binders may impart a nondesired and unacceptable mouth feel. Gelatin, if used as a binder, in addition to masking the cooling effect of xylitol, may not be

desired for ethnic reasons. Starches and other cariogenic fermentable carbohydrates, if utilized as binders, are not desirable because of their negative impact on oral health.
US 5,204,115 describes a directly compressible, non-cariogenic free flowing xylitol granulate having an average particle size of up to about 500 microns which consists of xylitol. and a pharmaceutically acceptable, non-cariogenic binder in the range of about 0.1% to about 5% by weight taken from the group consisting of polymerized reducing sugars, alkali carboxymethylcellulose and hydrogenated starch hydrolysate.
US 5,385,749 describes a directly compressible powdered xylitol composition comprising xylitol and at least one additive selected from the group consisting of mannitol,. pulverulent maltitol, maltodextrins, glucose syrups, hydrogenated glucose syrup, hydrogenated maltodextrins, said composition having a xylitol content of at least 60% by weight, based on the weight of the composition, produced by extrusion technique.
US 7,943,171 describes a method for preparing granules of active substances containing food fibers which consists of granulating the active substances mixed with branched malto¬dextrins having between 15 and 35% of 1.-6 glucoside bonds, a reducing sugar content less than 20%, a polymolecularity index less than 5 and a number average molecular weight equal or less than 4500 g/mol, the branched malto-dextrins constituting between 3 and 13 wt. % of the mixture to be granulated.
EP 0938301 Bl describes a lactitol granulate containing a binder in the range of about 2% to about 30% by dry weight selected from the group consisting of sugar alcohols, polymerized reducing sugars, alkali carboxymethylcellulose, hydrogenated starch hydrolysate, hydroxypropylcellulose, pharmaceutically acceptable cellulose derivatives, PVP, gum arabic and other pharmaceutically acceptable gums.
WO2006/119697 Al describes a xylitol granule directly compressible into tablet mainly comprising xylitol and polyvinyl pyrrolidone, and a process for preparing the same. Such granulate are highly moisture-sensitive and hence difficult to handle.
Surprisingly, the inventors of the present invention have found that the use of some pharmaceutically acceptable^ excipients 'suoji^as i^altode^trir^ greg^latjnizai^starch, corn

starch, hydroxypropylcellulose or mixtures thereof, as binders aid in providing a directly compressible, free flowing xylitol granulate, which can be compressed into tablets of high hardness and low friability, and yet have the cariostatic properties and a pleasant taste. The directly compressible xylitol granulate of the present invention allows its use in large scale commercial tableting processes to produce tablets with remarkable hardness, low friability, pleasant taste, and which are non-caripgenic and potentially cariostatic. OBJECTIVE OF THE INVENTION
An objective of the present invention is to provide compressible free flowing granulate and process for preparing the same.
Another objective of the present invention is to provide free flowing directly compressible granulate which contain xylitol.
Another objective of the present invention is to provide free flowing compressible granulate which contain xylitol in combination with a pharmaceutically acceptable binder optionally with one or more other pharmaceutically acceptable excipient(s).
Another objective of the present invention is to provide granulate compositions which are particularly suitable for use in the manufacture of solid dosage forms by a dry process.
Another objective of the present invention is to provide granulate compositions which are particularly suitable for use in the manufacture of solid dosage forms by direct compression method.
Another objective of the present invention is to provide granulate which have a pleasant taste and are also suitable for the preparation of taste-masked compositions.
Yet another objective of the present invention is to provide process for the preparation of free flowing compressible granulate.
Another objective of the present invention is to provide process for the preparation of free flowing compressible granulate containing xylitol.

Yet another objective of the present invention is to provide method of using the free flowing compressible granulate for the manufacture of solid dosage forms.
SUMMARY OF THE INVENTION
Aspects of the present invention relates to directly compressible free flowing granulate and process for preparing the same.
Aspects of the present invention also relates to free flowing compressible granulate which contain xylitol in combination with a pharmaceutically acceptable binder optionally with one or more other pharmaceutically acceptable excipient(s).
Aspects of the present invention also relates to the granulate composition which are particularly suitable for use in the manufacture of solid dosage forms by a dry process such as by direct compression method.
Aspects of the present invention relate to the granulate which have a pleasant taste and are also suitable for the preparation of taste-masked compositions.
Aspects of the present invention further relates to process for the preparation of free flowing compressible granulate containing xylitol.
Aspects of the present invention also relates to method of using the free flowing compressible granulate for the manufacture of solid dosage forms.
Aspects of the present invention further relates to a directly compressible free flowing xylitol granulate containing about 90% to about 99.9% by weight of xylitol, a pharmaceutically acceptable binder in the range of about 0.1% to about 10% by weight, and optionally one or more pharmaceutically acceptable excipient(s).
Aspects of the present invention further relates to a directly compressible free flowing xylitol granulate containing about 90% to about 99.9% by weight of xylitol and a pharmaceutically acceptable binder in the range of about 0.1% to about 10% by weight selected from a group comprising maltodextrin, starch, hydroxypropylcellulose, and mixtures thereof.

Aspects of the present -invention further relates to a process for preparing directly
compressible free flowing xylitol granulate comprising the following steps:
Step (a): Fluidizing Xylitol in fluid bed granulator,
Step (b): Preparation of aqueous solution of binder,
Step (c): Granulating Xylitol of step (a) by spraying the binder solution of step (b) onto the
Xylitol material of step (a) followed by drying, and
Step (d): Optionally sifting the granules of Step (c) through appropriate sieve to obtain the
desired granulate.
Aspects of present invention relates to tablets containing xylitol granulate which exhibit superior hardness, low friability, are non-cariogenic and manifest the taste profile and , metabolic properties of xylitol. Aspects of present invention relate to use a directly compressible free flowing xylitol granulate for the manufacture of formulations in the field of the food, nutraceuticals and pharmaceuticals.
DETALIED DESCRIPTION OF THE INVENTION
In an embodiment, the present invention provides directly compressible free flowing granulate and process for preparing the same.
In an embodiment, the present invention also provides free flowing compressible granulate which contain xylitol in combination with a pharmaceutically acceptable binder optionally with one or more other pharmaceutically acceptable excipient(s).
In an embodiment, the present invention also provides granulate compositions which are particularly suitable for use in the manufacture of solid dosage forms by a dry process such as by direct compression method.
The granulate of the present invention have a pleasant taste and are also suitable for the preparation of taste-masked compositions.
In another embodiment, the present invention provides process for the preparation of free flowing compressible granulate containing xylitol.

In yet another embodiment, the present invention provides method of using the free flowing compressible granulate for the manufacture of solid dosage forms.
In an embodiment, the present invention provides directly compressible free flowing xylitol granulate containing about 90% to about 99.9% by weight of xylitol, a pharmaceutically acceptable binder in the range of about 0.1% to about 10% by weight, and optionally one or more pharmaceutically acceptable excipient(s).
In a further embodiment, the present invention provides a directly compressible free flowing xylitol granulate containing about 90% to about 99.9% by weight of xylitol and a pharmaceutically acceptable binder in the range of about 0.1% to about 10% by weight selected from a group comprising maltodextrin, starch, hydroxypropylcellulose, and mixtures thereof.
In a further embodiment, the present invention further provides directly compressible free flowing xylitol granulate comprising about 95% to about 99.9% by weight of xylitol and a pharmaceutically acceptable binder in the range of about 0.1% to about 5% by weight wherein the said binder comprises maltodextrin.
In a further embodiment, the present invention relates to a directly compressible free flowing xylitol granulate comprising about 91.5% to about 99.9% by weight of xylitol, and a pharmaceutically acceptable binder in the range of about 0.1% to about 5% by weight, wherein the said binder comprises starch.
In a further embodiment, the present invention provides directly compressible free flowing xylitol granulate comprising about 97.5% to about 99.9% by weight of xylitol, and a pharmaceutically acceptable binder in the range of about 0.1% to about 5% by weight, wherein the said binder comprises hydroxypropylcellulose.
In a further embodiment, the present invention provides directly compressible free flowing xylitol granulate comprising about 90% to about 99.9% by weight of xylitol, and a pharmaceutically acceptable binder in the range of about 0.1% to about 10% by weight, wherein the said binder comprises maltodextrin, starch, hydroxypropylcellulose, or mixtures thereof.

In yet another embodiment, the present invention provides a process for preparing directly
compressible free flowing xylitol granulate comprising the following steps:
Step (a): Fluidizing Xylitol in fluid bed granulator,
Step (b): Preparation of aqueous dispersion of binder.
Step (c): Granulating Xylitol of step (a) by spraying the binder dispersion of step (b) onto the
Xylitol material of step (a) followed by drying, and
Step (d): Optionally sifting the granules of Step (c) through appropriate sieve to obtain the
desired granulate.
In yet another embodiment, the present invention provides a process for preparing directly
compressible free flowing xylitol granulate comprising the following steps :
Step (a): Fluidizing Xylitol in fluid bed granulator;
Step (b): Preparation of aqueous solution of maltodextrin;
Step (c): Granulating step (a) material by spraying the solution of step (b) followed by drying,
and
Step (d): Optionally sifting the granules of Step (c) to obtain the desired size granulate.
In yet another embodiment, the present invention provides a process for preparing directly
compressible free flowing xylitol granulate comprising the following steps:
Step (a): Fluidizing Xylitol material in fluid bed granulator,
Step (b): Preparation of aqueous solution of 5% w/w of maltodextrin as binder,
Step (c): Granulating Xylitol of step (a) by spraying the binder solution of step (b) onto the
Xylitol material of step (a) followed by drying, and
Step (d): Optionally sifting the granules of Step (c) through appropriate sieve to obtain the
desired granulate.
In yet another embodiment, the present invention provides a process for preparing directly
compressible free flowing x.ylitol granulate comprising the following steps:
Step (a): Fluidizing Xylitol in fluid bed granulator;
Step (b): Preparation of aqueous solution of maltodextrin and starch;
Step (c): Granulating step (a) material by spraying the solution of step (b) followed by drying,
and
Step (d): Optionally sifting the granules of Step (c) to obtain the desired size granulate.
In yet another embodiment, the present invention provides a process for preparing directly
compressible free flowing xylitol granulate comprising the following steps:

Step (a): Fluidizing Xylitol material in fluid bed granulator,
Step (b): Preparation of aqueous binder dispersion comprising 2.5% w/w of maltodextrin and
2.5% w/w of Starch,
Step (c): Granulating Xylitol of step (a) by spraying the binder dispersion of step (b) onto the
Xylitol material of step (a) followed by drying, and
Step (d): Optionally sifting the granules of Step (c) through appropriate sieve to obtain the
desired granulate.
In yet another embodiment, the present invention provides a process for preparing directly
compressible free flowing xylitol granulate comprising the following steps:
Step (a): Fluidizing mixture of Xylitol and starch in fluid bed granulator;
Step (b): Preparation of aqueous solution of maltodextrin;
Step (c): Granulating step (a) material by spraying the solution of step (b) followed by drying,
and
Step (d): Optionally sifting the granules of Step (c) to obtain the desired size granulate.
In yet another embodiment, the present invention provides a process for preparing directly
compressible free flowing xylitol granulate comprising the following steps:
Step (a): Fluidizing Xylitol and Corn starch material in fluid bed granulator,
Step (b): Preparation of aqueous solution of 2.5% w/w of maltodextrin as binder,
Step (c): Granulating Xylitol of step (a) by spraying the binder solution of step (b) onto the
Xylitol material of step (a) followed by drying, and
Step (d): Optionally sifting the granules of Step (c) through appropriate sieve to obtain the
desired granulate.
In yet another embodiment, the present invention provides a process for preparing directly
compressible free flowing xylitol granulate comprising the following steps:
Step (a): Fluidizing Xylitol in fluid bed granulator;
Step (b): Preparation of aqueous dispersion of hydroxypropylcellulose,
Step (c): Granulating step (a) material by spraying the dispersion of step (b) followed by
drying, and
Step (d): Optionally sifting the granules of Step (c) to obtain the desired size granulate.
In yet another embodiment, the present invention provides a process for preparing directly
compressible free flowing xylitol granulate comprising the following steps: ._,

Step (a): Fluidizing .Xylitol material in fluid bed granulator,
Step (b): Preparation of aqueous dispersion of 2.5% w/w of hydroxypropylcellulose as
binder,
Step (c): Granulating Xylitol of step (a) by spraying the binder dispersion of step (b) onto the
Xylitol material of step (a) followed by drying, and
Step (d): Optionally sifting the granules of Step (c) through appropriate sieve to obtain the
desired granulate.
In yet another embodiment, the present invention provides tablets containing xylitol granulate which exhibit superior hardness, low friability, are non-cariogenic and manifest the taste profile and metabolic properties of xylitol.
In yet another embodiment, the present invention provides use of a directly compressible free flowing xylitol granulate for the manufacture of formulations in the field of the food, nutraceuticals and pharmaceuticals.
In an embodiment, the present invention provides a method of producing directly compressible free flowing xylitol granulate with superior flow characteristics which can be used for tableting purposes, or can be filled into capsules or sachets, or can be filled into suitable containers.
In an embodiment, the present invention provides tablets containing xylitol granulate which exhibit appreciable hardness, low friability, are non-cariogenic and manifest the taste profile and metabolic properties of xylitol.
In a further embodiment, the present invention provides use of directly compressible free flowing xylitol granulate for the manufacture of formulations in the field of the food, nutraceuticals and pharmaceuticals.
The binder concentration is expressed in % w/w, which means % by weight of binder(s) to the total weight of granulate on dry weight basis. The binder solution can be prepared by dissolving or dispersing the required amount of binder in an aqueous solvent such as purified water with stirring. Optionally, the binder solution may be filtered to remove any undissolved traces of material in the solution.

The binder contemplated by the present invention is a pharmaceutical^ acceptable, non-cariogenic binder. Surprisingly and unexpectedly, maltodextrin functions as an excellent binder in this context. Maltodextrin is available from the Roquette Pharma, France as Gluicdex® in various grades. Maltodextrin is a non sweet nutritive saccharine polymer that consists of D-glucose units linked primarily by [a]-1—>4 bonds and that has a dextrose equivalent (D.E.) of less than 20. It is prepared as a white powder or concentrated solution by partial hydrolysis of corn starch, potato starch, or rice starch with safe and suitable acids and enzymes, followed by purification and spray drying. Various commercial grades of maltodextrin are available in the market. In an embodiment of the present. invention, Glucidex® IT 12 (maltodextrin) is used. Gluicdex® 12 has a dextrose equivalent of 11-14. Other suitable grades of maltodextrins including linear and branched variants are also useful according to the present invention.
Another binder is a cellulose derivative particularly hydroxypropylcellulose commonly called as HPC. Hydroxypropylcellulose is a derivative of cellulose with both water solubility and organic solubility. Hydroxypropylcellulose is described as partially substituted poly (hydroxypropyl) ether of cellulose. It is a white to slightly yellow colored odorless and tasteless powder. It is commercially available in different grades that have different * viscosities. HPC having molecular weight ranging between 50000-1250000 is useful. Hydroxypropylcellulose is widely used in oral and topical pharmaceutical formulations as binders, film coating and extended release matrix formers. According to the present invention, hydroxypropylcellulose can be used in the range of 0.1 - 15% w/w, or 0.1 - 10% w/w, or 0.1 - 5% w/w. In an embodiment, hydroxypropylcellulose available under the brand name Klucel® LF sourced from Aqualon Division is used in this invention. Other suitable grades of HPC are also useful according to the present invention.
Other binders useful according to the present invention include starch derivatives such as corn starch or pregelatinized starch. Pregelatinized starch is commercially available from Colorcon under the brand name Starchl500®. The corn starch or pregelatinized starch can be used in combination with maltodextrin. Other types of starch or other suitable grades of com starch or pregelatinized starch are also useful according to the present invention.

Other commonly used binders, and other cellulosic substances and dextrins can also be used according to the present invention.
Granulation of the xylitol and a binder or a mixture of binders can be achieved with any of the standard means of granulation known to the art. In an aspect of the process, milled xylitol is combined with aqueous binder solution, mixed in a blender, sieved and dried. The dried granulate is further sieved to produce particles of uniform size and shape. In another aspect particularly at an industrial scale, fluidized bed processor is used. Suitable commercial granulators or granulating systems include the Lodige horizontal blender (Gebruder Lodige GmbH) in combination with a fluidized bed dryer, the Glatt vertical fluidized bed granulator (Glatt GmbH, Binzen, West Germany), the Aeromatic vertical fluidized bed granulator (Aeromatic AG, Bubendorf, Switzerland) and the Schugi granulator (Schugi, BV, Lelystad, Holland). Other granulation devises known to those skilled in the art can be utilized according to the present invention. The granulate thus produced may be screened with a sieve to remove coarse particles. For example, a 30 mesh (0.6 mm) sieve can be used for this purpose. The coarse particles can be reworked, milled or dissolved for further use.
In an embodiment, the granulate of the present invention can be used as excipient in a tablet, alone or in combination with other excipients such as diluents, lubricants.
The granulate of the present invention can be utilized as a sweetening, flavoring or bulking agent and/or as a diluent to make formulations, optionally in combination with other sweeteners, polyols.and/or other binding agents.
The following examples serve to illustrate the embodiments of the present invention. However, they do not intend to limit the scope of the invention in any manner whatsoever. Further, it is obvious to those skilled in the art to come out with other similar composition for other dosage forms and substitute the equivalent excipients as described in this specification or with the one known to the industry.
EXAMPLES

s.
No. Ingredients Quantity (%w/w)

Example-I Example-H Example-Ill Example-IV
1 Xylitol 95.00 95.00 92.50 97.50
2 Maltodextrin 5.00 2.50 5.00 -
3 Pregelatinized starch - 2.50 - -
4 Corn Starch - - 2.50 -
, ..-v <- . -, ^ A—?= ^-~\- Z ■> A

5 Hydroxypropylcellulose - - - 2.50
6 Purified Water Q.s Q.s Q.s Q.s
Q.s - Quantity Sufficient Manufacturing process: Example-I:
Step (a): Xylitol is charged into a Fluid Bed Processor.
Step (b): An aqueous solution of 5% by weight of maltodextrin (based on the total weight of
granulate) is prepared and sprayed onto xylitol to obtain the granulate.
Step (c): The granulate thus obtained is dried under fluidized hot air.
Step (d): The dried granulate are sifted through #30 mesh sieve.
Example-II:
Step (a): Xylitol is charged into a Fluid Bed Processor.
Step (b): An aqueous dispersion.of 2.5% by weight of maltodextrin and 2.5%) by weight of
starch (based on the total weight of granulate) is prepared and sprayed onto xylitol to obtain
the granulate.
Step (c): The granulate thus obtained is dried under fluidized hot air.
Step (d): The dried granulate are sifted through # 24 mesh sieve.
Example-Ill:
Step (a): Xylitol and corn starch are charged into a Fluid Bed Processor.
Step (b): An aqueous solution of 5% by weight of maltodextrin (based on the total weight of
granulate) was sprayed onto xylitol to obtain the granulate.
Step (c): The granulate thus obtained is dried under fluidized hot air.
Step (d): The dried granulate are sifted through # 20 mesh sieve.
Example-IV:
Step (a): Xylitol is charged into a Fluid Bed Processor.
Step (b): An aqueous dispersion of 2.5% by weight of hydroxypropylcellulose (based on the
total weight of granulate) was sprayed onto xylitol to obtain the granulate.
Step (c): The granulate thus obtained is dried under fluidized hot air.
Step (d): The dried granulate are sifted through #30 mesh sieve.
We Claim:
1.. A directly compressible free flowing granulate comprising about 90% to about 99.9% by weight of xylitol and a pharmaceutically acceptable binder selected from a group comprising maltodextrin, starch, hydroxypropylcellulose and combinations thereof in a range of about 0.1% to about 10% by weight.
2. The directly compressible granulate of claim 1, wherein maltodextrin is present in an amount of about 2.5% to about 5 % by weight of the granulate.
3. The directly compressible granulate of claim 1, wherein starch is present in an amount of about 2% to about 4% by weight of the granulate.
4. The directly compressible granulate of claim 1, wherein starch is present in an amount of about 2.5% by weight of the granulate.
5. The directly compressible granulate of claim 1 wherein hydroxypropylcellulose is present in an amount of about 2% to about 4 % by weight of the granulate.
6. A process for preparing directly compressible free flowing xylitol granulate according to claim 1 comprising the following steps:
Step (a): Fluidizing Xylitol in fluid bed granulator;
Step (b): Preparation of aqueous solution of maltodextrin;
Step (c): Granulating step (a) material by spraying the solution of step (b) followed by drying,
and

Step (d): Optionally sifting the granules of Step (c) to obtain the desired size granulate.
7. A process for preparing directly compressible free flowing xylitol granulate according to
claim 1 comprising the following steps:
Step (a): Fluidizing Xylitol in fluid bed granulator;
Step (b): Preparation of aqueous solution of maltodextrin and pregelatinized starch;
Step (c): Granulating step (a) material by spraying the solution of step (b) followed by drying,
and
Step (d): Optionally sifting the granules of Step (c) to obtain the desired size granulate.
8. A process for preparing directly compressible free flowing xylitol granulate according to
claim 1 comprising the following steps:
Step (a): Fluidizing mixture of Xylitol and starch in fluid bed granulator;
Step (b): Preparation of aqueous solution of maltodextrin;
Step (c): Granulating step (a) material by spraying the solution of step (b) followed by drying,
and
Step (d): Optionally sifting the granules of Step (c) to obtain the desired size granulate.
9. A process for preparing directly compressible free flowing xylitol granulate according to
claim 1 comprising the following steps:
Step (a): Fluidizing Xylitol in fluid bed granulator;
Step (b): Preparation of aqueous dispersion of hydroxypropylcellulose,
Step (c): Granulating step (a) material by spraying the dispersion of step (b) followed by
drying, and
Step (d): Optionally sifting the granules of Step (c) to obtain the desired size granulate.

10. A directly compressible, free flowing xylitol granulate, according to any of the preceding claims, used for formulating pharmaceutical and/or nutraceutical finished dosage