(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT)

(19) World Intellectual PropertyOrganization

International Bureau(10) International Publication Number

(43) International Publication Date20 November 2014 (20.11.2014)

WO 2014/184806 A2P O P C T

(51) International Patent Classification: Not classified road, Thane (West) - 400602, Maharashtra (IN). S. WAD-HWANI, Jagdish; Jai Sai Villa, 4th floor, Flat No .401,

(21) International Application Number: Near Talwalkars gym, Netaji chowk, Ulhasnagar (East) -PCT/IN20 14/000323 421005, Maharashtra (IN).

(22) International Filing Date: (74) Agent: THAKUR, Sujit; Jupiter Law Partners, Office No.May 2014 (09.05.2014) 123, First Floor, Vipul Agora, M G Road, Gurgaon 122002

(25) Filing Language: English (IN).

(26) Publication Language: English (81) Designated States (unless otherwise indicated, for everykind of national protection available): AE, AG, AL, AM,

(30) Priority Data: AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY,1760/MUM/2013 17 May 2013 (17.05.2013) IN BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM,

(71) Applicant: ATHENA DRUG DELIVERY SOLUTIONS DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT,

PVT LTD. [IN/IN]; 602, 6th Floor, Star Hub, Tower II, HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR,

Sahar International Airport Road, Andheri (East), Mumbai KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME,

400059 (IN). MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ,OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA,

(72) Inventors: B. CHAUDHARI, Mahendra; Konark tower, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM,6th floor, Flat no.601, Nearby three petrol pump, Ghantali

[Continued on nextpage]

(54) Title: VOGLIBOSE ORALLY DISINTEGRATING COMPOSITION AND PROCESS FOR PREPARING THE SAME

(57) Abstract: Disclosed is a voglibose orally disintegrating composition, comprising: about 0.1 to about 0.2 percent by weight of voglibose; about 70 to about

. 100 0 percent by weight of mannitol 200; about 0.25 to about 1 percent by weightof colloidal silicon dioxide; about 10 to about 20 percent by weight of mannitol25; about 0.5 to about 1.5 percent by weight of a sweetener; about 0.25 to about1 percent by weight of a flavorant; about 5 to about 7 percent by weight of a dis-integrant; and about 1 to about 3 percent by weight of a lubricant.

<©00

00FIG.l

w o 2014/184806 A2 1I 11 II I III IIII I I I II I III ll ll III i ll

TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, Declarations under Rule 4.17:ZW.

— as to the identity of the inventor (Rule 4.17(ϊ))'

(84) Designated States (unless otherwise indicated, for even- — as to applicant's entitlement to apply for and be grantedkind of regional protection available): ARIPO (BW, GH, apatent (Rule 4.1 7(H))GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ,UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, Published:TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, — without international search report and to be republishedEE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, upon receipt of that report (Rule 48.2(g))LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK,SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ,GW, KM, ML, MR, NE, SN, TD, TG).

VOGLIBOSE ORALLY DISINTEGRATING COMPOSITION AND PROCESSFOR PREPARING THE SAME

FIELD OF THE INVENTION

[0001] The present invention generally relates to voglibose compositions,

and, more specifically, to orally disintegrating voglibose compositions comprising a

low dosage of voglibose.

BACKGROUND OF THE INVENTION

[0002] Voglibose is an alpha-glucosidase inhibitor used for lowering post¬

prandial blood glucose levels in people with diabetes mellitus. Conventional voglibose

tablets have been available for a ong time; however the disintegration of conventional

tablets is much slower resulting in decreased efficacy of the medicine. Also, for elderly

or children or people with an impaired swallowing function or people with decreased

saliva production, the oral intake of conventional tablets is a cumbersome process.

[0003] Now, orally disintegrating tablets (ODTs) are available. ODTs

differ from conventional tablets in that they are designed to be dissolved/disintegrated

in an oral cavity rather than swallowed whole. Accordingly, ODTs have been developed

such that the same medicine be orally administered in a simple and effective manner to

children, adults and people with impaired swallowing function and similar conditions.

Even a patient who is not suffering from any swallowing limitation will find it much

easier to take an ODT as compared to a conventional tablet. An additional reason to use

an orally disintegrating tablet is the convenience of a tablet that can be taken without

water.

[0004] In view of ease of administration, the ODTs have a rapid

disintegration rate as compared to conventional tablets. However, rapid disintegration

properties and high tablet hardness are generally contradicting properties, and therefore

ODTs cause chips and cracks of the tablets when divided because of insufficient tablet

hardness and high friability. Due to high disintegration and low hardness, even the

cracking or disintegration problems are faced in the course of production and/or

distribution.

[0005] On the other hand, due to high intake of voglibose, one or more of

the following side effects may be experienced: delay in digestion and absorption of

disaccharides, abdominal pain and swelling, increased flatus, intestinal obstruction like

symptoms, fulminant hepatitis, serious hepatic dysfunction with increased AST (GOT),

ALT (GPT), LDH, gamma GTP or ALP, jaundice, diarrhea, loose stools, borborygmus,

anorexia, nausea, vomiting, heartburn, anemia, numbness, edema, blurred vision, hot

flushes, malaise, weakness hyperkalemia, and increased serum amylase. To avoid these

conditions, it is preferable to take a lower dosage of voglibose. However, uniformity and

efficacy of the medicine is an issue with lower dosage compositions.

[0006] Accordingly, there is a need for an orally disintegrating low dosage

voglibose composition that provides better uniformity and consistent reliability and

efficacy of the voglibose medicine; and that is safe to manufacture, distribute and

administer. Also, what is required is a voglibose orally disintegration composition that

has excellent disintegration and dissolution properties while having an appropriate

hardness to avoid any damage in the course of production and/or distribution.

SUMMARY OF THE INVENTION

[0007] To achieve the foregoing and other objects and needs, the present

invention provides a voglibose composition that provides better uniformity in low

dosage and consistent reliability and efficacy of the voglibose medicine. Also, the

present invention provides a voglibose orally disintegration composition that has

excellent disintegration and dissolution properties while having an appropriate hardness

to avoid any disintegration in the course of production and/or distribution.

[0008] In one aspect, the present invention provides voglibose orally

disintegrating composition, comprising: about 0.1 to about 0.2 percent by weight of

voglibose; about 70 to about 80 percent by weight of mannitol 200; about 0.25 to about

1 percent by weight of colloidal silicon dioxide; about 10 to about 20 percent by weight

of mannitol 25; about 0.5 to about 1.5 percent by weight of a sweetener; about 0.25 to

about 1 percent by weight of a flavorant; about 5 to about 7 percent by weight of a

disintegrant; and about 1 to about 3 percent by weight of a lubricant.

[0009] in one specific aspect, the voglibose composition comprises about

0.15 percent by weight of voglibose.

[0010] In another aspect, voglibose orally disintegrating composition is in

form of an orally disintegrating tablet having a disintegrating time of about to about

8 seconds and a hardness of about 20 Newton to 40 Newton.

[0011] In another aspect, the present invention provides a process for

preparation of a voglibose composition. The process comprises: mixing voglibose in an

aqueous medium to form a voglibose solution; adding mannitol 25 to the voglibose

solution to form a mannitol and voglibose solution; adding a sweetener and a flavorant

to the mannitol and voglibose solution to form a granulation solution; loading the

granulation solution onto a fluidized blend of mannitol 200 and colloidal silicon dioxide

to form drug granules; blending the drug granules with a lubricant and a disintegrant to

form a lubricated blend; and compressing the lubricated blend.

BRIEF DESCRIPTION OF THE DRAWINGS

[0012] The advantages and features of the present invention will become

better understood with reference to the following detailed description and claims taken

in conjunction with the accompanying drawing, in which:

[0013] FIG. 1 illustrates a flow process for preparation of a voglibose

orally disintegrating composition, in accordance with an exemplary embodiment of the

present invention; and

[0014] FIG. 2 illustrates details of the flow process of FIG. 1, in

accordance with an exemplary embodiment of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

[0015] The exemplary embodiments described herein detail for illustrative

purposes are subject to many variations in structure and design. It should be

emphasized, however, that the present invention is not limited to a particular voglibose

orally disintegrating composition and preparation process for the same, as shown and

described. It is understood that various omissions and substitutions of equivalents are

contemplated as circumstances may suggest or render expedient, but these are intended

to cover the application or implementation without departing from the spirit or scope of

the claims of the present invention. Also, it is to be understood that the phraseology and

terminology used herein is for the purpose of description and should not be regarded as

limiting.

[0016] The use of terms "including," "comprising," or "having" and

variations thereof herein is meant to encompass the items listed thereafter and

equivalents thereof as well as additional items. Further, the terms, "a" and "an" herein

do not denote a limitation of quantity, but rather denote the presence of at least one of

the referenced item.

[0017] The present invention provides a voglibose orally disintegrating

composition (hereinafter referred to as the "voglibose composition"). The voglibose

composition of the present invention is a low dosage form with greater efficacy,

uniformity and reliability. In specific embodiments, as would be described below in the

examples, the voglibose composition comprises a low dosage form of about 0.1 to about

0.2 percent by weight of voglibose of the total voglibose composition.

[0018] Also, the voglibose composition has excellent disintegration and

dissolution properties while having an appropriate hardness to avoid any disintegration

in the course of production and/or distribution. In specific embodiments, as would be

described below in the examples, the voglibose composition has a disintegrating time of

about 12 to about 18 seconds, while having hardness of about 20 Newton (N) to about

40 Newton (N).

[0019] The composition comprises voglibose, mannitol 200, colloidal

silicon dioxide, mannitol 25, a sweetener, a flavorant, and a lubricant. In one

embodiment the voglibose composition comprises: about 0.1 to about 0.2 percent by

weight of voglibose; about 70 to about 80 percent by weight of mannitol 200; about

0.25 to about 1 percent by weight of colloidal silicon dioxide; about 10 to about 20

percent by weight of mannitol 25; about 0.5 to about 1.5 percent by weight of a

sweetener; about 0.25 to about 1 percent by weight of a flavorant; about 5 to about 7

percent by weight of a disintegrant; and about 1 to about 3 percent by weight of a

lubricant.

[0020] Voglibose (INN and USAN, trade name Voglib, marketed by

Mascot Health Series) is an alpha glucosidase inhibitor used for lowering post-prandial

blood glucose levels in people with diabetes mellitus. Voglibose inhibits the hydrolase

(alpha gluosidase) enzyme for disaccharides that catalyzes decomposition of

disaccharides into monosaccharides in the intestine. Thereby, it delays the digestion and

absorption of carbohydrate, resulting in improvement of postprandial hyperglycemia.

As used in the present invention, voglibose is obtained from Biocon.

[0021] As used herein, mannitol refers to a white, crystalline sugar alcohol

with the chemical formula (C6H (OH)6) . As used in the present invention, mannitol 200

(also known as Pearlitol 200) is obtained from Roquette. The Pearlitol range offers a

unique blend of exceptional physical and chemical stability, with great organoleptic,

non-carcinogenic, sugar-free properties. Together with its versatile powder properties, it

is the key to a wide range of oral and injectable applications, and for use in different

processes (wet or dry granulation, direct compression, compaction or freeze-drying).

[0022] As used herein, colloidal silicon dioxide refers to a fumed silica

prepared by vapour-phase hydrolysis of a silicon compound, such as silicon

tetrachloride. The product itself is usually a submicron, fluffy, light, loose, bluish-white,

odourless and tasteless amorphous powder which is commercially available from a

number of sources, including Cabot Corporation (under the trade name Cab-O-Sil®);

Degussa, Inc. (under the trade name Aerosil®); Huber Engineered Materials (Huber

GL100 and GL200®); Wacker (Wacker HDK ®); and E.I. DuPont & Co. As used in

the present invention, colloidal silicon dioxide is obtained from Degussa. Colloidal

silicon dioxide is also known as Aerosil, colloidal silica, fumed silica, light anhydrous

silicic acid, silicic anhydride, and silicon dioxide fumed, among others. A variety of

commercial grades of colloidal silicon dioxide are produced by varying the

manufacturing. Also, the colloidal silicon dioxide is used herein as a glidant that serves

as a materia] for improving powder flow since colloidal silicon dioxide is inert and

doesn't dissolve in water.

[0023] As used in the present invention, mannitol 25 (a so known as

Pearlitol 25) is obtained from Roquette. The Pearlitol range offers a unique blend of

exceptional physical and chemical stability, with great organoleptic, non-carcinogenic,

sugar-free properties. Together with its versatile powder properties, it is the key to a

wide range of oral and injectable applications, and for use in different processes (wet or

dry granulation, direct compression, compaction or freeze-drying).

[0024] As used herein, the sweeteners can include aspartame, saccharin

sodium, dipotassium glycyrrhizinate, stevia, thaumatin, acesulfame K, sucralose, and

combinations of the foregoing. In one embodiment, the sweetener is aspartame.

Aspartame is an artificial, non-saccharine sweetener used as a sugar substitute in some

foods and beverages. Aspartame is a methyl ester of the aspartic acid/phenylalanine

dipeptide. As used in the present invention, the aspartame is obtained from Nutra sweet.

[0025] The flavoring agents that can be used include natural and artificial

flavors. These flavors may be one or more o synthetic flavor oils and flavoring

aromatics, and/or oils, oleo resins and extracts derived from plants, leaves, flowers,

fruits, etc., and combinations thereof. Representative flavor oils include: spearmint oil,

cinnamon oil, peppermint oil, clove oil, bay oil, thyme oil, cedar leaf oil, oil of nutmeg,

oil of sage, and oil of bitter almonds. Also useful are artificial, natural or synthetic fruit

flavors such as vanilla, chocolate, coffee, cocoa and citrus oil, including lemon, orange,

grape, lime and grapefruit and fruit essences including apple, pear, peach, strawberry,

raspberry, cherry, plum, pineapple, apricot and so forth. These flavorings can be used

individually or in admixture. Commonly used flavors also include mints such as

peppermint, artificial vanilla, cinnamon derivatives, and various fruit flavors, whether

employed individually or in admixture. Flavorings such as aldehydes and esters

including cinnamyl acetate, cinnamaldehyde, citral, diethylacetal, dihydrocarvyl

acetate, eugenyl formate, p-methylanisole, and so forth may also be used. n one

embodiment, the flavorant is liquid banana. As used in the present invention, the liquid

banana is obtained from IFF.

[0026] In one embodiment, the disintegrant is polyplasdone XL. As used

herein polyplasdone XL belongs to the category of polyplasdone crospovidones that are

used in drug formulations. Not only are polyplasdone crospovidones highly effective

tablet disintegrants; Polyplasdone superdisintegrants can improve the rate and extent of

drug dissolution. As used herein, polyplasdone XL aids in increasing the dissolution

rate of poorly soluble drugs compared with other superdisintegrants. As used in the

present invention, the polyplasdone XL is obtained fr o BASF/ISP.

[0027] Lubricants can be added to granules both during the final mixing

phase before compression and during granulation. Among the traditional solid

lubricants, calcium, magnesium, and zinc salts of stearic acid, partially hydrogenated

vegetable oils, polyethylene glycols, polyoxyethylene monostearate, talc, sodium

benzoate, sodium laurylsulfate, magnesium oxide can be used. In one embodiment

lubricant is used in the voglibose composition powder blending applications for anti-

adherent activity (i.e., prevent sticking to punch faces and die walls), glidant activity

(i.e., improve the flowability of the powder or granules), and lubricant activity (i.e.,

reduce friction, transfer heat, and prevent corrosion during the process). In one

embodiment, the lubricant is magnesium stearate.

[0028] As used herein, magnesium stearate refers to a white powdered

substance having the chemical formula Mg(C H3502) . It is a salt containing two

equivalents of stearate (the anion of stearic acid) and one magnesium cation (Mg +).

Magnesium stearate is used herein to serve as a lubricating medium for the voglibose

composition. Magnesium stearate prevents ingredients from sticking to manufacturing

equipment during the compression of chemical powders into solid tablets. Magnesium

stearate has advantages over other lubricants because of its high melting temperature,

high lubricity at a low concentration, large covering potential, general acceptance as

safe, nontoxicity, and its excellent stability profile. As used in the present invention, the

magnesium stearate is obtained from Ferro.

[0029] Further, again colloidal silicon dioxide may be added. Such

addition of colloidal silicon dioxide may be required to improve the flow property of

the lubricant (also interchangeably referred as lubricated blend).

[0030] Further, the present invention provides a process for preparation of

the voglibose orally disintegrating composition (hereinafter referred to as process).

Referring to FIGS. 1 and 2, the process is illustrated. In FIG. 1, the primary process

steps are illustrated, while in FIG. 2 the details of each step are illustrated. In the below

description of the process, the reference numerals are used individually and/or

collectively from both the FIGS. 1 and 2.

[0031] At step 102, the process initiates by mixing voglibose in an

aqueous medium to form a voglibose solution. The stirring is done using a propeller

stirrer in a stainless steel vessel (SS vessel). In an embodiment, the aqueous medium

used is purified water. The stirring for voglibose is carried out for about 15 minutes.

Next at step 104, the mannitol 25 powder is added to the voglibose solution and stirred

to form a mannitol and voglibose solution. Next at step 106, a sweetener and flavorant

is added to the mannitol and voglibose solution to form a granulation solution. The

solution is stirred for about 30 minutes to make a smooth lump free solution. In an

embodiment, the sweetener is aspartame and the flavorant is liquid banana. At boxes

202 and 204, illustrated are the details of the granulation solution formed from

voglibose, mannitol 25, aspartame and liquid banana in purified water. Herein, at box

208 the granulation solution is interchangeably referred to as "drug loading solution".

[0032] At step 108, the granulation solution is loaded onto a fluidized

blend of mannitol 200 and colloidal silicon dioxide to form drug granules. The fluidized

blend is formed by mixing mannitol 200 and colloidal silicon dioxide and sifting

through 40 mesh sieve fitted to a vibratory sifter, as illustrated in boxes 206 and 208.

Although a mesh sieve of particular dimension is mentioned above, it will be evident to

a person skilled in the art to use mesh sieves of varying dimensions for obvious

variations.

[0033] At box 210, the details of the loading of the drug or the granulation

solution are mentioned. Specifically, the drug loading is performed by spraying the

granulation solution on fluidized blend of mannitol 200 and colloidal silicon dioxide in

a fluid bed coater at controlled parameters. In an embodiment, the fluid bed coater is a

Ganson's fluid bed coater and the drug loading is performed at a temperature of about

25 to about 35 degree centigrade. After the granulation step or drug loading step, as

illustrated at box 212, the drug granules are sifted through 36 mesh sieve fitted to a

vibratory sifter. Although a mesh sieve of particular dimension is mentioned above, it

will be evident to a person skilled in the art to use mesh sieves of varying dimensions

for obvious variations.

[0034] At step 1 0, the drug granules are blended with a lubricant and a

disintegrant to form a lubricated blend. In one embodiment, as illustrated at box 214,

polyplasdone XL (the disintegrant), magnesium stearate (the lubricant) and optionally

colloidal silicon dioxide is added to the drug granules. Next, as illustrated at box 216,

the lubricant is sifted through 36 mesh sieve fitted to a vibratory sifter. Although a mesh

sieve of particular dimension is mentioned above, it will be evident to a person skilled

in the art to use mesh sieves of varying dimensions for obvious variations. At box 218

in FIG. 2, the details of the blending step 10 are mentioned. The blending is performed

in a blender for about 30 minutes.

[0035] Next, at step 112, the lubricated blend is compressed to form the

voglibose orally disintegrating composition. At box 220 in FIG. 2, the details of the

compression step 112 are mentioned. The compression is performed using stable

tooling, specifically at a 16 inch station at about 16 to about 20 rpm. Although

particular station dimension and rpm are mentioned above, it will be evident to a person

skilled in the art to use varying station dimensions and rpms for obvious variations.

[0036] Also, as illustrated at box 220, in one embodiment, the

compression is a tablet compression for forming voglibose orally disintegrating tablets

(also referred to as Voglibose ODTs). In another embodiment, the voglibose orally

disintegrating composition may be directly available in ready-to-use sachets.

[0037] The process may further comprise packing the voglibose

compositions. At box 222, the details of the packing are mentioned. In an embodiment,

the packing is done using ALU-ALU blister material at a production speed of about 6

to about 20 blisters per minute.

[0038] The description of the voglibose orally disintegrating composition

of the present invention is further illustrated by the following non-limiting examples.

However, a person skilled in the art would recognize that, the specific examples are

intended to illustrate, not limit, the scope of the present invention.

EXAMPLES

EXAMPLE 1

[0039] In Example 1, a process for preparing a 0.2 milligram (mg)

voglibose orally disintegrating tablet is described. The process for preparing voglibose

composition of the present invention was initiated by mixing 1.05 gram (g) of voglibose

in purified water (about 570 g) and stirred to form a voglibose solution. Next, 105.6 g of

mannitol 25 power was added to the voglibose solution and stirred to form a mannitol

and voglibose solution. Next, 6.8 g of aspartame (sweetener) and 3.4 g of liquid banana

(flavorant) was added to the mannitol and voglibose solution to for a granulation

solution. The solution was stirred for about 30 minutes to make a lump free solution.

Thereafter, the granulation solution was loaded onto a fluidized blend of mannitol and

colloidal silicon dioxide to form drug granules. The fluidized blend was formed by

mixing 504.2 g of mannitol 200 and 6 g of colloidal silicon dioxide and sifting through

a 40 mesh sieve fitted to a vibratory sifter. The loading of the drug/granulation solution

was performed in a Ganson's fluid bed coater. The amount of total solid drug granules

(also known as "voglibose drug granules") was about 627.05 g.

[0040] Next, the drug granules were sifted through 36 mesh sieve fitted to

a vibratory sifter. Thereafter, 426.06 g of drug granules were blended with a lubricant

and a disintegrant to form a lubricated blend. (In this way about 60 to 80 percent of

drug granules prepared in each batch is taken to proceed with the preparation of the

voglibose composition, and remaining is used for testing the parameters of the drug

granules). The lubricant comprises 9.07 g of magnesium stearate; and the disintegrant

comprises 27.86 g of polyplasdone XL. Further, colloidal silicon dioxide may be added

again to improve the flow property of the lubricant. The same is added as per desired

lubricant properties (for example, in one embodiment, about 0.65 mg per tablet).

Finally, the lubricated blend was compressed to form the voglibose composition. The

solvent, i.e., purified water does not remain in the final composition. In Table 1 below,

the different ingredients of the voglibose composition are depicted along with details on

pharmacopeial reference, the vendor from whom the ingredient was obtained, percent

by weight of each ingredient and weight in mg of each ingredient.

TABLE 1

Polyplasdone XLEP BP IP BASF / ISP 6.15 8.0

(disintegrant)

Colloidal silicondioxide EP/BP/IP Degussa 0.5 0.65

(Aerosil 200)

Magnesium stearateEP/BP/IP Ferro 2 2.6

(lubricant)

Total 100 130

[0041] Specifically, the process and composition details described in

Example 1 and Table 1 is used for preparing 0.2 mg voglibose orally disintegrating

tablets (hereinafter referred to as 0.2 mg voglibose ODT). Multiple experiments were

conducted to form 0.2 mg voglibose, i.e, to form voglibose ODT comprising 0.2 mg of

voglibose. For example, experiment for batches 1, 2 and 3 were conducted for forming

voglibose drug granules and experiments for batches 4, 5, and 6 were conducted for

forming the final voglibose ODT. It was found all batches resulted in substantially the

same content indicating consistency in uniformity of content that is desirable for lower

dosage compositions of 0.2 mg. Also, it was found that the 0.2 mg voglibose ODT had

desirable disintegration dissolution properties, while still having appropriate hardness.

All such properties for the different batches are illustrated in Tables 2 and 3 below.

TABLE 2

Average weight of tablets 132.28 g 133.55 mg 130.74 mg

Diameter 7 mm flat bevelled edged plain on the surface

3.2 - 3.35Thickness 3.2 - 3.3 mm 3.2 - 3.3 mm

mm

Hardness 25 - 30 N 24 - 30 N 27 - 30N

Disintegrating time 12 seconds 14 seconds 3 seconds

Friability 0.13 0.1 0.14

TABLE 3

EXAMPLE 2

[0042] I Example 2, a process for preparing a 0.3 milligram (mg)

voglibose orally disintegrating tablet is described. The process for preparing voglibose

composition of the present invention was initiated by mixing 1.05 grams(g) of

voglibose in purified water (about 570 g) and stirred to form a voglibose solution. Next,

105.6 g of mannitol 25 power was added to the voglibose solution and stirred to form a

mannitol and voglibose solution. Next, 6.8 g of aspartame (sweetener) and 3.4 g of

liquid banana (flavorant) was added to the mannitol and voglibose solution to form a

granulation solution. The solution was stirred for about 30 minutes to make a lump free

solution. Thereafter, the granulation solution was loaded onto a fluidized blend of

mannitol and colloidal silicon dioxide to form drug granules. The fluidized blend was

formed by mixing 504.2 g of mannitol 200 and 6 g of colloidal silicon dioxide and

sifting through a 40 mesh sieve fitted to a vibratory sifter. The loading of the

drug/granulation solution was performed in a Ganson's fluid bed coater. The amount of

total solid drug granules (also known as "voglibose drug granules") was about 627.05 g.

[0043] Next, the drug granules were sifted through 36 mesh sieve fitted to

a vibratory sifter. Thereafter, 451.8 g of drug granules were blended with a lubricant

and a disintegrant to form a lubricated blend. (In this way about 60 to 80 percent of

drug granules prepared in each batch is taken to proceed with the preparation of the

voglibose composition, and remaining is used for testing the parameters of the drug

granules). The lubricant comprises 9.73 g of magnesium stearate; and the disintegrant

comprises 29.85 g of polyplasdone XL. Further, colloidal silicon dioxide may be added

again to improve the flow property of the lubricant. The same is added as per desired

lubricant properties (for example, in one embodiment, about 0.98 mg per tablet). .

Finally, the lubricated blend was compressed to form the voglibose composition. The

solvent, i.e., purified water does not remain in the final composition. In Table 4 below,

the different ingredients of the vogl ibose composition are depicted along with details on

pharmacopeial reference, the vendor from whom the ingredient was obtained, percent

by weight of each ingredient and weight in mg of each ingredient.

TABLE 4

Colloidal silicondioxide ΕΡ/ΒΡ Ρ Degussa 0.38 0.75

(Aerosil 200)

Mannitol 25EP/BP/IP Roquette 15.5 30.3

(Pearlitol 25)

Aspartame EP/BP/IP Nutra sweet 1 1.95

Flavor - LiquidIn house IFF 0.5 0.98

Banana

Purified Water* In house In house

IntermediateBlending

Components

Polyplasdone XLEP/BP/IP BASF / ISP 6.15 2

(disintegrant)

Colloidal silicondioxide EP/BP/IP Degussa 0.5 0.98

(Aerosil 200)

Magnesium stearateEP/BP/IP Ferro 2 3.9

(lubricant)

Total 100 195

[0044] Specifically, the process and composition details described in

Example 2 and Table 4 is used for preparing 0.3 mg voglibose orally disintegrating

tablets (hereinafter referred to as 0.3 mg voglibose ODT). Multiple experiments were

conducted to form 0.3 mg voglibose ODT, i.e, to form voglibose ODT comprising 0.3

mg of voglibose. For example, experiment for batches 7, 8 and 9 were conducted for

forming voglibose drug granules and experiments for batches 10, 11, and 12 were

conducted for forming the final voglibose 0.3 mg ODT. It was found al batches

resulted in substantially the same content indicating consistency in uniformity of

content that is desirable for lower dosage compositions of 0.3 mg. Also, it was found

that the 0.3 mg voglibose ODT had desirable disintegration dissolution properties, while

still having appropriate hardness. All such properties for the different batches are

illustrated in Tables 5 and 6 below.

TABLE 5

Ingredients Batch size = 2500 tablets

Batch numbers of 0.3 g tablets 10 11 12

Voglibose drug granules (From Batch No.) 7 8 9

Voglibose drug granules 451.8 450.73 448.58

Polyplasdone XL 29.85 29.85 29.85

Magnesium stearate 9.73 9.73 9.73

Total 491.38 490.31 488.16

Average weight of tablets 196.55 196.12 195.26

Diameter 8 mm flat bevelled edged plain on the surfaci

Thickness 3.4 -3.6 mm 3.5 —3.6 mm 3.4 - 3.6 n

Hardness 24 - 35 N 24 - 35 N 26 - 32

Disintegrating time 18 seconds 16 seconds 7 secon<

Friability 0.1 0.13 0.14

TABLE 6

Limit LT 80% in 30 minutes

Moisture content 1.8% .6% 1.5%

[0045] The foregoing descriptions of specific embodiments of the present

disclosure have been presented for purposes of illustration and description. They are not

intended to be exhaustive or to limit the present disclosure to the precise forms disclosed,

and obviously many modifications and variations are possible in light of the above

teaching. The embodiments were chosen and described in order to best explain the

principles of the present disclosure and its practical application, to thereby enable others

skilled in the art to best utilize the present disclosure and various embodiments with

various modifications as are suited to the particular use contemplated. (It is understood that

various omission and substitutions of equivalents are contemplated as circumstance may

suggest or render expedient, but such are intended to cover the application or

implementation without departing from the spirit or scope of the claims of the present

disclosure).

CLAIMS

1. A voglibose orally disintegrating composition, comprising:

about 0.1 to about 0.2 percent by weight of voglibose;

about 70 to about 80 percent by weight of mannitol 200;

about 0.25 to about 1 percent by weight of colloidal silicon dioxide;

about 10 to about 20 percent by weight of mannitol 25;

about 0.5 to about 1.5 percent by weight of a sweetener;

about 0.25 to about 1 percent by weight of a flavorant;

about 5 to about 7 percent by weight of a disintegrant; and

about 1 to about 3 percent by weight of a lubricant.

2. The voglibose orally disintegrating composition of claim 1, wherein

the lubricant is magnesium stearate.

3. The voglibose orally disintegrating composition of claim 1, wherein

the disintegrant is polyplasdone XL.

4. The voglibose orally disintegrating composition of claim 1, wherein

the voglibose composition comprises about 0.15 percent by weight of voglibose.

5. The voglibose orally disintegrating composition of claim 1, wherein

the sweetener is aspartame.

6. The voglibose orally disintegrating composition of claim 1, wherein

the flavorant is liquid banana.

7. The voglibose orally disintegrating composition of claim 1, wherein

the voglibose orally disintegrating composition is in form of an orally disintegrating tablet

having a disintegrating time of about 12 to about 18 seconds and a hardness of about 20

Newton to 40 Newton.

8. A process for preparation of a voglibose orally disintegrating

composition, comprising:

mixing voglibose in an aqueous medium to form a voglibose solution;

adding mannitol 25 to the voglibose solution to form a mannitol and

voglibose solution;

adding a sweetener and a flavorant to the mannitol and voglibose solution to

form a granulation solution;

loading the granulation solution onto a fluidized blend of mannitol 200 and

colloidal silicon dioxide to form drug granules;

blending the drug granules with a lubricant and a disintegrant to form a

lubricated blend; and

compressing the lubricated blend.

9. The process of claim 8, further comprising packing the voglibose

orally disintegrating composition.

10. The process of claim 8, wherein the voglibose composition

comprises

about 0.1 to about 0.2 percent by weight of voglibose;

about 70 to about 80 percent by weight of mannitol 200;

about 0.25 to about 1 percent by weight of colloidal silicon dioxide;

about 0 to about 20 percent by weight of mannitol 25; and

about 0.5 to about 1.5 percent by weight of a sweetener;

about 0.25 to about 1 percent by weight of a flavorant;

about 5 to about 7 percent by weight of a disintegrant; and

about to about 3 percent by weight of a lubricant.

. The process of claim 10, wherein the voglibose orally disintegrating

composition comprises about 0.1 percent by weight of voglibose.

12. The process of claim 8, wherein the aqueous medium is purified

water.

13. The process of claim 8, wherein the lubricant is magnesium stearate.

14. The process of claim 8, wherein the disintegrant is polyplasdone XL.

5. The process of claim 8, wherein the sweetener is aspartame.

16. The process of claim 8, wherein the f!avorant is liquid banana.

17. The process of claim 8, wherein loading the granulation solution

onto a fluidized blend of mannitol 200 and colloidal silicon dioxide is performed in a

fluid bed coater.