FORM 2
THE PATENTS ACT, 1970 • (39 of 1970) COMPLETE SPECIFICATION
[See section 10; rule 13]
TITLE "PROCESS FOR PREPARATION OF WATER DISPERSIBLE TABLET"
TORRENT PHARMACEUTICALS LTD., a company incorporated under the Companies Act, 1956, of Torrent House, Off Ashram Road, Near Dinesh Hall, Ahmedabad 380 009, Gujarat, India
The following specification particularly describes the invention, the nature of this invention (and the manner in which it is to be performed):

PROCESS FOR PREPARATION OF WATER DISPERSIBLE TABLET
FIELD OF INVENTION
The present invention relates to a process for preparation of
water dispersible tablet of an active pharmaceutical
ingredient or pharmaceutically acceptable salt thereof and one
or more adjuvants and without the use Of swellable clay. This
invention further relates to a process for preparing the
formulation.
BACKGROUND OF THE INVENTION
The oral administration of solid dosage forms, for example tablets, capsules, often presents ingestion problems for the patient, especially in case of childr or or old people. In order to get around this problem other forms of pharmaceutical formulations are resorted to, for exqmple chewable tablets, dispersible tablets and monodose sachets, the contents of which are to be dissolved or suspended .in water and taken orally.
The therapeutic action of a pharmaceuti cally active ingredient depends much on the formulation characteristics. One of the prerequisites of an acceptable formulation is the ease with which it can be administered e.g. to epilepsy patients. The act of swallowing solid dosage form by these patients may become difficult with the possibility of choking. To achieve optimum therapeutic benefit of the anti-epileptic drug, it is desirable to present the drug in a formulation, which can rapidly disperse in water, so that wher needed the drug may be taken in the form of an aqueous d:ispersion. The route of

administration described above can be advantageous, for children and elderly people, who often have troubles in swallowing medicines in any disease, in solid form, such as tablets or capsules.
A representative anti-epileptic drug, Lamotrigine, of the phenyltriazine group is chemically unrelated to existing antiepileptic drug (AED's). Its chemical name is 3,5-diamino-6(2,3-dichlorophenyl)-1,2,4-triazine, its molecular formula is C9H7N5Ci2. It is disclosed in EP-A-0021121.
While developing a new pharmaceutical composition, the ingredients should satisfy the demands of the pharmaceutical production process. Lamotrigine, for example, presents bad flow properties and this, combined with its significant concentration in the tablet, poses a serious restriction on its formulation by simple manufacturing techniques like direct compression (Pharmaceutical Dosage forms - volume 3, Leon Lachman - 2nd edition, 1990, pg. 11 and The theory and practice of Industrial pharmacy Leon Lachman - 3rd (Indian) edition, 1986 pg.183,294).
It is also important that the tablet should possess appropriate physico-chemical properties relating to hardness, stability, friability, disintegration time, etc.
PRIOR ART
US 5225197 discloses dispersible tablet, facilitated by the
inclusion of an acid/base couple, in which the base liberates carbon dioxide when components are dissolved in water. It is also known to provide effervescent formulations of medicaments in water-soluble form, so as to provide clear solutions of the

Antibiotics. The manufacture of these tablets however require expensive methods, strict environment control and critical packaging to retain its dispersibility characteristics.
US 5556639 discloses that in spite of using various disintegrating agents (incorporated both internally and externally to the preformed granules) such as sodium starch glycollate (e.g. Explotab™), cross-linked povidone (e.g. Kollidon CL) and a cross-linked sodium carboxymethylcellulose
(e.g. Ac-Di-Sol™) a satisfactory water dispersible tablet could not be produced. Furthermore, an ion exchange resin
(Amberlite 1RP88) was also employed as a disintegrating agent and incorporation of surface active agents (e.g. sodium lauryl sulphate and sodium docusate) in an attempt to improve tablet wetting and penetrating of water during dispersion, resulted in high disintegration times. The said patent thus utilizes an unique property of a known adjuvant - VeegumTM, a swellable clay, during granulation which is essential to effect proper dispersion.
US. 5047247 discloses the dispersible tablet of dihydroxergotoxine methanesulfonate prepared on the basis of known method of granulating the ingredients. However, it need to be noted that granulation step is time consuming. The avoidance of this step may lead to avoid time cycle for each batch production, man power, utilities, equipment usage etc. associated with the said step of granulation.
EP181650 discloses dispersible tablets containing cyclandelate, which yield a fine dispersion when brought in contact with water of 2 0 degree C; the tablets consist of a rapidly dispersible core containing one or more active

substances, which is covered by a coating that is also rapidly dispersible. This form is particularly suitable for active ingredients that are prone to recrystallisation and/or sublimation, but represents a considerable complex production process employing an organic solvent. The use of such solvents pose a serious threat to the environment and strict controls to ensure that the residual amounts remaining in the formulation are within acceptable limits as laid down by ICH Q3C guideline.
GB 2086725 A discloses rapidly disintegrating tablets, which after disintegration, form dispersion containing the isolated, mostly coated, micro particles. Even in those cases where the microparticles used are of small size-e.g. of 0.3 to 0.6 mm diameter, when swallowed, they are perceived as individual grains in the mouth in an unpleasant manner and may be caught on the spaces between the teeth. Generally spoken, the dispersion prepared from such tablets produces a certain feeling of hoarseness in the mouth. Furthermore, often liquid foods, e.g. apple sauce or marmalade, are needed to administer the tablets known in the art. The use of the latter has the following disadvantages: (a) The person in need of the drug always has to take in food simultaneously when swallowing a formulation of the invention. But food intake can often be completely undesired in such situations, e.g. for reason of avoiding increase of weight. (b) Drug absorption may be influenced by the food taken in simultaneously in an undesired manner.

OBJECT OF THE INVENTION
The object of the present invention is to prepare the water dispersible tablet containing active pharmaceutical ingredient or pharmaceutically acceptable salt thereof and one or more adjuvants.
Next object of the invention is to prepare the water dispersible tablet containing active pharmaceutical ingredient or pharmaceutically acceptable salt thereof and one or more adjuvants and without using swellable clay.
Another object of the present invention is to prepare the said water dispersible tablet of anti-epileptic drug, lamotrigine.
Still another object of the invention is to develop a chewable tablet, which may be dispersed in a small quantity of water to yield a fine, flavored dispersion and suitable for oral administration.
The further object of the invention is to manufacture water dispersible tablets, by simpler and less expensive way (the production process does not require any special equipment) and to achieve tablets disintegration time within less than 3 minute to a perfectly homogenous dispersion, in which, when taken up by mouth and swallowed, no individual grains can be perceived any more.
Further object of the invention is to get 100% dissolution of Lamotrigine in 0.IN hydrochloric acid is achieved within 15 minutes.

Still another object of the invention is to prepare the water dispersible tablet, administerable to mammal in need thereof, without the need of any liquid foods.
DETAILED DESCRIPTION OF THE INVENTION
The oral administration of solid dosage forms, for example tablets, capsules, often presents ingestion problems for the patient, especially in case of children or people. The therapy of- chronic disease conditions like epilepsy requires that the drug becomes available to the patient's bloodstream rapidly. The most preferred dosage form for this purpose is the pharmaceutical suspension. However, there are other problems associated with such dosages. They suffiBr from limited shelf-life and being multi-dose preparations, lead to inaccurate dose measurement causing dosage variation. Especially in children, where the dose is low, this may lead to serious side effects.
The solution to this problem is the unit dosage form, either solid oral dosage like tablets and capsules or single dose powder for reconstitution in sachets. The later suffers from the disadvantage of being bulky and difficult to carry, reducing the patient compliance. The problem with shaped dosages like tablets and capsules is in terms of swallowing difficulty, primarily for children and elderly people. This becomes particularly important for epilepsy patients, since the act of swallowing may become difficult with the possibility of choking. To achieve optimum therapeutic benefit of the drug, it is desirable to present the ■ drug in a formulation, which can rapidly disperse in water, so that when

needed the drug can be taken in the form of an aqueous dispersion.
Dispersible tablets offer the advantages of the suspension without the problems of instability, dosage variations, difficulty in swallowing and size limitations (bulk). Similar advantages are existent for chewable tablets.
The dispersible tablet of this invention typically comprises from 10% to 60% by weight of the active pharmaceutical compound or pharmaceutically acceptable salts thereof, in relation to the total formulation weight.
The dispersible tablet of this invention preferably comprises 2 mg to 2 50 mg lamotrigine.
The manufacture of the dispersible tablets is simpler and much less expensive, the production not requiring any special equipment, conditions and packaging - as is required for the effervescent tablets.
The process of manufacture is not so susceptible to moisture as effervescent tablets and hence the controls required can be same as those used in the manufacture of conventional tablets.
The process according to the instant invention does not use any organic solvents, which are hazardous, a major environmental pollution issue and require strict process control and lengthy and expensive validations to ensure that the residual solvent levels are below the stipulated limits set forth by the ICH Q3C guideline (Impurities: Guidelines for residual solvents).

A further advantage of the formulation is that it disintegrates rapidly in water and releases 100% drug in less than 15 minutes in 0.IN HCl. This improved dissolution aids in rapid and complete bioavailability.
The critical characteristics of the dis^ersible tablets are :
1. Rapid disintegration in water
2. Fineness of the resultant dispersior1-
The particle size distribution of the dispersion resulting from stirring the tablet in water are as shown in Table - 1:
Table - 1

The dispersion obtained should have finer particle size distribution with broad requirement of all particles to be less than 710 μm Further, particle size can be preferably 600
μm and less.
The active ingredients or substances are comprising of the following therapeutic classes but not limited to general anesthetics, angiotensin converting enzyme inhibitors, angiotensin receptor antagonist, antacids, anti- rheumatoid,

anti-asthmatics, antiallergics, antiarrhythmic, antibiotics, anti-convulsants, anti-depressants, anti-diarrheals antiemetics, anti-histamines, anti-infective, anti-bacterials, antiviral, antifungal, antiprotozoals, anti-inflammatory agent s, ant i-nauseant s, ant i-hyperlipidemic drugs, anti-parkinson, antihelmintics, anti-psychotics, antipyretics, anti-spasmodic, antithrombotic drugs, anticoagulants, antiplatelets, anti-tumor drugs, anti-uricaemic drugs, anxiolytic agents, appetite stimulants, appetite suppressants, bronchodialators, antihypertensives(diuretics, beta-blockers, ACE inhibitors, calcium channel blockers, vasodialators),chelating agents, cholecystokinin antagonists, cognition activators, cough suppressants, erythropoietic drugs, fertility agents, antidiarrhoeals, laxatives, antiulcer agents, growth regulators, immunomodulating agents, neuroleptics, neuromuscular agents, potassium channel blocker, potassium channel opener, prostaglandins, respiratory stimulants, selective aldosterone receptor blocker, sedatives & hypnotics, synthetic hormones, tachykinin nk 1 antagonist, vaso-constrictors and vertigo agents and vitamins.
The pharmaceutically active ingredient, which can be formulated into the water dispersible dosage form may be selected, from but not limited to, the group comprising AAE581, AAG5 61, abacavit sulfate, abciximab, ABT-510, ABT-751, acarbose, acetaminophen, acyclovir, aesloratadine, AG-1749, aldosterone antagonist, alendronate sodium, almotriptan, alprazolam, aminocaproic acid, amlodipine besylate, AMP397, amphetamine, anagrelide hydrochloride, anastrozole, aprepitant, aripiprazole, atorvastatin calcium, atrasentan, AZD0328, AZD0865, AZD0902, AZD2171, AZD3409, AZD4282, AZD4750, AZD5106, AZD714 0, azelnidipine, azithromycine, balsalazide

disodium, bazedoxifene, betaxolol hydrochloride, bicalntamid,
BILN-2061, biperiden HCl, bisoprolol fumarate, bromfenac
sodium, buformin, candesartan cilexetil, captopril,
carboplatin, carvedilol, CCI-779, cefadroxil, ceftriaxone
sodium, celecoxib, CEP 7055, cerivastatin, cetrizine HCl,
CHC12103, chlorthalidone, CHS13340, ciglitazone,
cilastazole, ciprofloxacin, clindamycin, clofapine,
clonazepam, clopidogrel bisulfate, clorazepate dipotassium,
clorpropamide, clozapine, CP-122,721, CP-526,555, CP-529,414,
CRF-1 antagonists, CS-003, CS-011, CS-023, CS-502, CS-505, CS-
706, CS-747, CS-866, cyclophosphamide, cyclosporine,
deloratadine, dexmethylphenidate HCl, dextroamphetamine
sulfate, diclofenac sodium, dicyclomine hydrochloride,
digoxin, diltiazem, divalproex sodium, docetaxel,
dofetilide, domperidone, doxazosin mesylate,
doxercalciferol, doxorubicin HCl, dronedarone, dulaxetine,
emiglitate, enalapril maleate, enbrel, endesartan,
englitazone, enoxaparin sodium, enzothiadiazine, eplernone,
eplivanserin, epoetin alpha, eprosartan, eptifibatide,
erythromycin, escitalopram, esomeprazole magnesium, esters
of ampicillin, estradiol, estropipate, ethacrynate sodium,
etoricoxib, exemestane, famotidine, fexofenadine .HCl,
f idalestat, fluoxetine, fluoxetine HCl, f luticazone
peopianate, fluvastatin sodium, fluvoxamine maleate,
fondaparinux sodium, frovatriptan, FTY72 0, fudosteine,
fulvestrant, gabapentin, galantamine HCl, galopentin,
ganirelix acetate, gemitatrine HCl, glatiramer acetate,
glibenclamide (glyburide), glibornuride, gliclazide,
glimepiride, glipizide, gliquidone, glisoxepid, gosereline
acetate implant, granisetron, guanabenz. acetate, guanylate
cyclase inhibitors, haloperidol, hydralazine,

hydrochlorothiazide, hydromorphone HCl, hydroxyurea, ICL670, idraparinux, imatinib mesylate, indapamide, infliximab, ipratropium bromide, irbesartan, isosorbide 5-imononitrate, isosorbide dinitrate, isotretinoin, itrozole tablets, J695, ketorolac trimethamine, KUC 7483, lactobionate, 1AF237, lafutidine, lamotrigine, landiolol, latanoprost, leflunomide, letrozole, levetiracetarn, levofloxaine, levonorgestrel, levothroxine sodium, levothyroxine sodium, linezolid, liothyronine sodium, lisinopril, loperamide, loratidine, lorazepam, losartan, lovastatin, ludrocortisone acetate, mabthera, MCC-135, meloxicam, mephalan, metformin hydrochloride, methylphenidate HCl, MH-15E, miglitol, minoxidil, misoprostol, mometasone furote-monohydrate, montelkast sodium, montelukast sodium, moxifloxacin HCl, MS 209, MS 2 75, naratriptan hydrochloride, nateglinide, nebirapine, nebivolol, neorecormon, neteglinide, niacin, nicorandil, nifedipine, nitricoxide, nitroprusside, NK-104, NKS 104, NM 283, norethindrone acetate, norgestrel, NS 2330, octreotide acetate, olanzepine, olmesartan, omeprazole, ondensetron HCl, orlistat, osanetant, oseltamivir phosphate, oxaliplatin, oxcarbazepine, oxistat, oxprenolol, oxybutynin chloride, paloxetine HCl, pantoprazole sodium, paroxetine, paroxetine HCl, pazufloxacin, pemoline, pentoxyphylline, perindopril, phenbutamide, picotamide, pimecrolimus, pioglitazone, potassium chloride, pralnacasan, pravastatin sodium, propranolol, prucolapride, PTK787, quetiapine, quetiapine fumarate, quinapril, R1068, R1204, R-14244 0, R143 9, R144 0, R14 53, R14 87, R1518, R154 9, R1559, R411, R4 50, R673, R701, R744, rabeprazole sodium, radOOl, raloxifene HCl, ramipril, ranitidine hydrochloride, renzapride, RHIL-11, ribavarin, rimonabant, risedronate

sodium, risperidone, rituximab, rivastigmine tartrate, rofecoxib, roloxifene HCl, ropinirol, rosiglitazone maleate, rosuvastatin, SAB3 78, salmeteyol xinafoate, saredutant, serm 6471, sertraline HCl, sildenafil citrate, simvastatin, sirolimus, sitafloxacin, sodium valproate, somatropin, sotalol, SR 123781, SSR 126517, SSR 180575, SSR 250411, SSR 591813, sulodexide, sumatriptan succinate, T-1249, TAK-013, TAK-370, TAK-559, TAK-637, tamsuloin HCl, TAP-144SR, TCH346, TCV - 116, telbivudine, telmisaltan, telmisartan, temozolomide, terbinafine HCl, timolol, tipranavir, tirapazamine, tolazamide, tolbutamide, tolcyclamide, tolterodine taltacate, tolterodine tartrate, tomoxetine HCl, topiramate, topotecan HCl, tramadol, trandolapril, trastuzumab, troglitazone, Uk-338,003, UK-369,003, valacyclovir HCl, valdecoxib, valsartan, valtorcitabine, vancomycin hydrochloride, vegf tki, venlafaxine, voglibose, voriconazole, warfarin sodium, xaliproden, zafirlukast, zalcitabine, ziprasidone, ziprasidone mesylate, zofenopril calcium, zol44 6, zoledronic acid, Zolpidem tartarate, zp 10, etc. or pharmaceutically acceptable slat thereof.
More preferably the active ingredients are selected from anti-epileptic class comprising the active ingredient from the group but not limited to Carbamazepine, chloral hydrate, clobazam,clonazepam, diazepam, etizolam, felbamate, flunarizine, fosphenytoin, phenytoin, gabapentin, isofloxythepin, lamotrigine, levetiracetam, lorazepam, phenobarbitone, primidone, pregablin, succinimides, tiagabine, topiramate, valproic acid and salts, vigabatrin, zonisamide and pharmaceuticallyy acceptable salts thereof.

The essential ingredients, which impart the above desired properties to the dispersible tablets, are disintegrants. In the sense used in this invention they are agents, which imbibe water making rapid swelling and quick disintegration,possible. The disintigrants used in the present invention are selected, but not limited, from the group comprising of corn or potato starch or modified starches {sodium carboxymethyl starch etc.), microcrystalline cellulose, cross-linked sodium carboxymethyl cellulose (e.g. Ac-di-sol), cross-linked povidone (e.g. Kollidon CL™) and ion exchange resins (e.g. Amberlite 1RP88).
The disintigrants in the dosage form ranges from 1% to 15% by weight.
The disintigrants according to the instant invention does not contain swellable clay. Swellable clay includes layered clays such as smetites, porous fibrous clay minerals and synthetic clay materials related in structure to layered clays and porous fibrous clays.
The tablets may contain other pharmaceutically acceptable excipients i.e. binder, which facilitate the compression of the powdery material and gives the tablet strength. The binder may be selected, but not limited to, from the group comprising of cellulose and its derivatives, polyvinyl pyrrolidone (Kollidon K25 or K30), polyvinyl alcohol, starch etc.
The binder in the dosage form ranges from 2% to 5% by weight.
The tablets may also contain other pharmaceutically acceptable excipients i.e. fillers. Fillers may be selected from, but not limited to the group comprising of lactose, sugar, mannitol,

cellulose and co-processed cellulosics {e.g. Cellactose™, Prosolv™) etc. Of particular importance are co-processed excipients like cellulose co-processed with silica (e.g. Cellactose™, Prosolv™). The filler outperforms traditional microcrystalline cellulose (MCC) alone and blends of MCC and colloidal silicon dioxide. It has a mean particle size of 40 to 90 microns leading to better compactibility and self-lubricating properties. It accommodates poorly flowing activities and aids the dispersion of the particles after fast tablet disintegration.
The filler in the dosage form ranges from 5% to 60% by weight of the formulation.
Lubricants and glidants are adjuvants used in the formula to reduce inter-particle and die-wall friction and enhance the powder flow due to their large surface area e.g. stearic acid and its salts, talc, colloidal silica (e.g. Aerosil 200™) and hydrophilic lubricants like sodium stearyl fumarate (e.g. Pruv™) etc. These adjuvants may be added in a percentage between 0.5% to 7% by weight of the formulation.
Sweetners and flavours as used in this invention are agents which mask the unpleasant organoleptic (aroma and taste) properties of the drug and other excipients e.g. saccharides, aspartame, cyclamate, dextrates etc- Suitable flavours comprise of black currant flavour, strawberry flavour, raspberry flavour, banana flavour, mint flavour, lemon flavour, peach flavour, mixed fruit flavour, menthol etc. These adjuvants may be added in a percentage between 1% to 4% by weight.

Optionally a dye such as titanium dioxide may be added to the tablet to impart colour. The tablet may also contain a wetting agent or a hydrophilic surfactant such as sodium lauryl sulphate, docusate sodium, poloxamers, polysorbates etc. to aid water penetration into the tablet for its rapid disintegration.
The tablets may optionally be film-coated with cellulose based film-formers to increase the aesthetic appeal. Example of such film formers include various grades of hydroxypropyl methylcellulose, microcrystalline cellulose, carageenan, methacrylic acid copolymers etc.
According to the present invention tablets or minitablets can be prepared and these words can be taken interchangeably.
In vitro tests show that the dispersible tablet dissolves in water within a very short period of time (T85% less than or equal to 15 minutes).
The test to demonstrate the dispersibility of the tablet is defined in the British Pharmacopoeia 3001. volume II, which states that the dispersion obtained within a period of 3 minutes passes through a sieve screert with a nominal mesh aperture of 710 μm.
The formulation can be prepared by various methods such as given below:
(I) The manufacturing procedure of the dispersible tablet comprises of fine screening the dru9 and appropriate amounts of suitable excipients to remove any lumps and blending them together (except lubricants) to a uniform distribution. The lubricant(s) is then added and blended

for further 2 to 3 minutes to yield a free flowing powder blend. The resultant blend is tableted into tablets of desired size and shape.
(II) The procedure of dry granulation comprises of fine
screening the drug and appropriate amounts of suitable
excipients to remove any lumps and passing them together
through a roller compacter (eg. Chilsonator, Fitzpatrick)
to obtain drug compacts. These are then screened through
ASTM #2 0 sieve to yield granules which are lubricated by
blending alongwith the lubricant(s) and the resulting
blend is tableted into tablets of desired size and shape.
(III) The procedure of drug granulation and direct
compression comprises of granulating the drug and
appropriate amounts of suitable excipients in the
fluidized bed processor (eg. Glatt or Aeromatic) and
blending the resulting drug granules with other
excipients to a uniform distribution. The lubricant(s) is
then added and blended for further 2 to 3 minutes to
yield a free flowing powder blend. The resultant blend
is tableted into tablets of desired size and shape.
The use of dispersible tablets thus obtained present a series of benefits:
1. They are suitable to treat patients with difficulty in swallowing shaped dosage forms in absence of liquid food.
2. Dosage is flexible and accurate following dissolution in known volume of water, unit dose may be repeated according to the regime of treatment,

3. Their compact size and shape allow packaging into blister
packs, enhancing ease of handling to ensure better
patient compliance and therefore raising the efficacy of
treatment.
Alternatively the formulation can also be prepared by granulation methods like wet granulation or dry granulation methods.
The tablet manufactured by both above method comply with British Pharmacopoeia as discussed above.
Throughout this specification and the appended claims it is to be' understood that the words "comprise" and "include" and variations such as "comprises", "comprising", "includes", "including" are to be interpreted inclusively, unless the context requires otherwise. That is, the use of these words may imply the inclusion of an element or elements not specifically recited.
The present invention has been described by way of example only, and it is to be recognized that modifications thereto which fall within the scope and spirit of the appended claims, and which would be obvious to a skilled person based upon the disclosure herein, are also considered to be included within the invention.

Example 1 :
Dispersible tablets were prepared as per the following pharmaceutical formula:
Table - 2

To manufacture 2500 tablets :
Lamotrigine (250g), Mannitol (206.25g), SMCC (lOOg), CCS (lOg) and CSD (1.875g) were sifted through Sieve ASTM#40 and the flavour (6.25g) and Aspartame (18.75g) were sifted through sieve ASTM#60 and blended in an octagonal blender for 15 minutes. Magnesium stearate (15.63g) sifted through sieve ASTM#60 was added to above blend and mixed for 2 minutes. The lubricated blend was compressed into tablets on a 16-station rotary compression machine with 8.7mm diameter round flat beveled punches as per the following parameters.


Table - 3
The tablets may also be prepared with the above formula by following dry granulation method. In this method, the drug is mixed with mannitol and passed twice through the roll-compacter and sized through ASTM#20 sieve to yield granules. The granules are blended with other ingredients as above and compressed into tablets.
Example 2 :
The tablets are manufactured similar to those in Example 1.
Table - 4


Table - 5

Example 3 :
Table - 6

The tablets are manufactured similar to those in Example 1.
Table - 7


Example - 4
Table - 8

The tablets are manufactured similar to those in Example 1.
Table - 9


Example - 5
Table - 10

The tablets are manufactured similar to those in Example 1.
Table - 11




Example 6 :
Table - 12
Table - 13
I

The drug along with CSD and CPV is granulated with PVP in binder solution in a fluidized bed processor (Glatt) and the
resulting , granules are directly compressed into tablets with 8. 7mm diameter round flat beveled punches as per the following parameters.

Table - 14

Example 7 :
Table - 15

Table - 16

The tablets are manufactured similar to those in Example 4.


Table - 17
The said tablets of other strengths may be prepared by varying. the weight of the tablet using the same £>lend as above.

J

Annexure -1
We claim:
1. The process for preparation of water dispersible tablet of pharmaceutically acceptable active ingredient comprising, active pharmaceutical ingredient or salt thereof (10 - 60% w/w), disintigrant (1 - 15% w/w), filler (5 - 60% w/w), lubricant (0.5 - 7 %w/w), glident or anti-adherent, flavoring agents, sweetener, colorant and other pharmaceutically acceptable excipient(s) such as herein described, comprising the following steps:
(i) a fine screening of the Pharmaceutically active ingredient or pharmaceutically acceptable salt thereof with one or more adjuvant, except lubricant and
(a) blending in a suitable blender or
(b) passing through roller compactor or
(c) granulating using an aqueous solvent in a fluidized bed processor to obtain granules
(ii) the drug compacts / granules produced by step ( b & c) are then screened to yield granules
(iii) mixture of (i.a) or (ii) is blended along with the flavoring agent, sweetener and/or colorant to attain uniformity
(iv) the lubricant is added to the above powder mixture and blended to obtain lubricated blend
(v) compressing the lubricated blend obtained in step (iv) above to tablets.
Page 1 cif 3

2. The process as claimed in claim 1, wherein diluents is selected from the group consisting of mannitol, microcrystalline cellulose and its co-processed derivatives with colloidal silicon dioxide or lactose, sugar, mannitol, Hydroxypropylcellulose (HPC), starch, and any combination thereof.
3. The process as claimed in claim 1, wherein the disintigrant is selected from the from the group comprising of corn or potato starch or modified starches (sodium carboxymethyl starch, sodium starch glycollate etc.), microcrystalline cellulose, cross-linked sodium carboxymethyl cellulose (e.g. Ac-di-sol), cross-linked povidone (e.g. Kollidon CL™) and ion exchange resins.
4. The process as claimed in claim 1, wherein the lubricant is selected from magnesium stearates, sodium stearyl fumarate and talc.
5. The process as claimed in claim 1, wherein the active pharmaceutical ingredient is lamotrigine.
6. The process as claimed in claim 1 and 5, wherein active pharmaceutical ingredient, lamotrigine in the range of 2 mg to 250 mg.
7. The process as claimed in claim 1, wherein flavouring agent is selected from the group comprising of black currant flavour, strawberry flavour, raspberry flavour, banana flavour, mint flavour, lemon flavour, peach flavour, and mixed fruit flavour.
8. The process as claimed in claim 1, wherein preferable colorant used is a lake.
9. The process as claimed in claim 1, wherein of croscarmeHose ranges between 0.5% and 6% w/w and more preferably 1% and 5% w/w.
10. The process as claimed in claim 1, wherein the said microcrystalline cellulose or its co-processed derivatives have a mean particle size between 40 and 90 microns.

11. The process as claimed in claim 1, wherein the tablet comprises;
(i) 10 - 60% w/w lamotrigine as a pharmaceutical^ acceptable active ingredient,
(ii) 10 to 60% w/w of diluent selected from the group comprising of mannitol or microcrystalline cellulose or its co-processed derivatives,
(iii) 2 to 5% w/w of a binder selected from the group comprising of starch and cellulose derivatives and polyvinyl pyrrolidone,
(iv) 0.5 to 6% w/w of disintigrant selected from the group comprising of crospovidone or croscarmellose,
(v) 1 to 10% w/w of disintigrant sodium starch glycollate and
(vi) 0.5 to 5% w/w of diluent colloidal silicon dioxide or silicic acid.
12. The process for preparation of water dispersible tablet is substantially as herein
described with reference to foregoing examples.