FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
[See section 10 and rule 13]
TITLE OF THE INVENTION : VOGLIBOSE ORALLY DISINTEGRATING
COMPOSITION AND PROCESS FOR PREPARING THE SAME
1. APPLICANT
(a) NAME - Athena Drug Delivery Solutions Pvt Ltd.
(b) NATIONALITY - Indian
(c) ADDRESS - 602,6th Floor, STAR HUB, Tower II, Sahar International
Airport Road, Andheri (East), Mumbai 400059, India
PREAMBLE TO THE DESCRIPTION
COMPLETE
The following specification particularly describes the invention and the manner in which it is to be performed.

VOGLIBOSE ORALLY DISINTEGRATING COMPOSITION AND PROCESS FOR 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 long 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 12 to about 18 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 (C6H8(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 material 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 (also 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 of 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. In 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 from 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(C18H35O2)2• 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 110, 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 110 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 16 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 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.
[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

Ingredients Pharmacopeial reference Vendor %WAV Mg/tablet
Drug Granules 0.2
Voglibose In house Biocon 0.15 0.2
Mannitol 200 (Pearlitol 200 ) EP/BP/IP Roquette 73.8 95.9
Colloidal silicon dioxide
(Aerosil 200) EP/BP/IP Degussa 0.38 0.5
Mannitol 25 (Pearlitol 25) EP/BP/IP Roquette 15.5 20.2
Aspartame EP/BP/IP Nutra sweet 1 1.3
Flavor - Liquid Banana In house IFF 0.5 0.65
Purified Water* In house In house
Intermediate Blending Components
Polyplasdone XL (disintegrant) EP/BP/IP BASF / ISP 6.15 8.0
Colloidal silicon dioxide
(Aerosil 200) EP/BP/IP Degussa 0.5 0.65

Magnesium stearate (lubricant) EP/BP/IP Ferro 2 2.6
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

Ingredients Batch size = 3500 tablets
Batch numbers of 0.2 mg tablets 4 5 6
Voglibose drug granules (From Batch No.) 1 2 3
Voglibose drug granules 426.06 430.5 420.67
Polyplasdone XL 27.86 27.86 27.86
Magnesium stearate 9.07 9.07 9.07
Total 462.99 467.43 457.6

Average weight of tablets 132.28 mg 133.55 mg 130.74 mg
Diameter 7 mm flat bevell ed edged plain on the surface
Thickness 3.2-3.3 mm 3.2-3.3 mm 3.2-3.35

mm
Hardness 25-30N 24-30N 27-30N
Disintegrating time 12 seconds 14 seconds 13 seconds
Friability 0.13 0.11 0.14
TABLE 3

Batch No. 4 5 6
Assay 0.197mg 0.201 mg 0.198 mg
(Limit 95-105%) (98.3%) (100.5%) (98.8%)
MIN-99.4%
MIN-96.9% MIN-99.8% MAX-
Uniformity of content MAX-102.4% MAX-104.9% 104.2%
(85-115%,RSD<6%) AVG-100.2% AVG-102.4% AVG-
%RSD-2.3 %RSD-1.7 102.4% %RSD-1.6
Dissolution
(Paddle, 50 rpm, 500 ml, 0.01N HC1) 95.2% 96.5% 95.5%
Limit NLT 80% in 30 minutes
Moisture content 1.8% 1.58% 1.5%
EXAMPLE 2
[0042] In 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 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 4

Ingredients Pharmacopeial reference Vendor %W/W Mg/tablet
Drug Granules 0.3
Voglibose In house Biocon 0.15 0.3
Mannitol 200 (Pearlitol 200 ) EP/BP/IP Roquette 73.8 143.85
Colloidal silicon dioxide
(Aerosil 200) EP/BP/IP Degussa 0.38 0.75
Mannitol 25 (Pearlitol 25) EP/BP/IP Roquette 15.5 30.3
Aspartame EP/BP/IP Nutra sweet 1 1.95

Flavor - Liquid Banana In house IFF 0.5 0.98
Purified Water* In house In house
Intermediate
Blending Components
Polyplasdone XL (disintegrant) EP/BP/IP BASF / ISP 6.15 12
Colloidal silicon dioxide
(Aerosil 200) EP/BP/IP Degussa 0.5 0.98
Magnesium stearate (lubricant) EP/BP/IP Ferro 2 3.9
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 all 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 mg 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 surface
Thickness 3.4-3.6 mm 3.5-3.6 mm 3.4-3.6 mm
Hardness 24-35N 24-35N 26-32N
Disintegrating time 18 seconds 16 seconds 17 seconds
Friability 0.1 0.13 0.14
TABLE 6

Batch No. 10 11 12
Assay (Limit 95-105%) 0.301 mg (100.2%) 0.302 mg (100.7%) 0.302 mg (100.7%)
Uniformity of content
(85-115%,RSD<6%) Complies Complies Complies
Dissolution
(Paddle, 50 rpm, 500 ml, 0.01N HC1)
Limit NLT 80% in 30 minutes 96.0% 95.3% 95.9%
Moisture content 1.8% 1.6% 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).

We Claim:
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 10 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 I 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.
11. The process of claim 10, wherein the voglibose orally disintegrating
composition comprises about 0.15 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.
15. The process of claim 8, wherein the sweetener is aspartame.
16. The process of claim 8, wherein the flavorant 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.