FORM 2
THE PATENTS ACT, 1970
(39 OF 1970)
&
THE PATENTS RULES, 2003
(See Section 10; Rule 13)
TITLE
PHARMACEUTICAL FORMULATIONS
APPLICANT
CIPLA LIMITED
AN INDIAN COMPANY
OF 289 BELLASIS ROAD, MUMBAI, CENTRAL, MUMBAI 400 008,
MAHARASHTRA
INDIA
The following specification particularly describes the nature of the invention and the manner in which it is to be performed.

1
Pharmaceutical Formulations
Technical Field:
5 The present invention provides a oral dosage formulation of active pharmaceutical ingredient and process for producing the said formulation.
Background and Prior Art:
10 The pharmaceutical industry employs a variety of dosage formulations for orally administering medicinal agents to patients. Typical formulations for oral administration include liquid solutions, emulsions, or suspensions, as well as solid forms such as capsules or tablets (as used herein, the term "tablet" means any shaped and compressed solid dosage form, including caplets). Since these conventional solid dosage formulations are usually
15 intended for adults who can easily swallow large tablets, any disagreeable taste of the active ingredient often need not be taken into account in formulating the medicine, unless there is a provision or means to prevent the taste from being apparent during the short time when the medicine is in the mouth. Such means may include the provision of an appropriate coating on the tablet; the use of a capsule form (the gelatin outer shell of the capsule keeps the active
20 ingredient inside until the capsule has been swallowed); or simply firmly compressing a tablet so that it will not begin to disintegrate during the short time that it is intended to be in the mouth.
A major requirement of a desirable oral form is that it must be palatable, since an unpalatable 25 formulation greatly increases the risk of a patient neglecting to take a medication. A further requirement of desirable oral dosage form is that it must be bioavailable; that is, once the formulation reaches the stomach, the individual particles should release the active ingredient rapidly and completely to ensure that substantially all of the active ingredient is absorbed. In cases where the active ingredient is particularly unpalatable and somewhat unstable, it may 30 be difficult, if not impossible, to produce a solid form that fulfills both of these requirements (i. e. palatable and bioavailable).

Palatability and "mouth feel" are among the most important characteristics to be considered in providing fast dissolving or disintegrating solid dosage forms, or matrix, for a drug. Unfortunately, many drugs have a bitter or otherwise unpalatable taste, or an unacceptable mouth feel, which make such drugs unsuitable for administration as fast dissolving or fast 5 disintegrating dosage forms. Much research has been devoted to designing techniques and approaches to mask the bitter taste of drug in dosage forms.
Simple approaches include adding chemical mediating, flavoring or sweetening ingredients to the composition, which thereby mask the bitterness of the drug. When simple approaches 10 are ineffective, drug modifying approaches are used in which the dosage form is so formulated that the drug's dissolution in the mouth is retarded or prevented by physical and/or chemical means. One such approach to retard by physical means is to embed or encapsulate the drug within a wall or barrier material that physically separates it from the saliva.
15 Alternative approaches of the prior art include microencapsulating unpleasant taste active agent in a coating of ethyl cellulose or a mixture of ethyl cellulose and hydroxyprbpyl cellulose or other cellulose derivatives to provide chewable taste-masked products. These prior art products, however, suffer from the disadvantage that the polymer coating may release the active agent in an inconsistent fashion and may not provide immediate release.
20
A number of references are known which describe pharmaceutical compositions of unpalatable medicinal agents which are coated with a taste masking coating in order to hide the unpleasant taste.
25 EP0650353 (to Smithkline Beecham Corp., filed on June 4, 1993) discloses medicament cores coated with methacrylate ester copolymers which mask the bitter and unpleasant taste of the medicament.
US5275823 (to Smithkline French Lab, filed on December 23, 1991) discloses a chewable 30 tablet that includes granulate of a histamine H2-receptor antagonist and Eudragit El00, and an admixture of a taste-masking extragranular water-insoluble hygroscopic excipient.

3 EP0523847 (to McNeil PPC Inc., filed on June 12, 1992) discloses a chewable medicament tablet that includes a medicament coated with a taste-masking amount of a polymer blend of dimethylaminoethyl methacrylate and neutral methacrylic acid esters and a polymer selected from cellulose acetate and cellulose triacetate. 5
US4708867 (to Key Pharmaceuticals Inc., filed on March 8, 1984) discloses a mini pellet dosage form of prednisone. The dosage form includes a nonpareil seed coated with a first layer of the drug and a second layer of a copolymer of dimethylaminoethyl methacrylate and methyl methacrylate.
10
US4760093 (to American Home Products, filed on October 2], 1986) discloses a taste neutral powder form of spray-dried acetaminophen which includes about 60% to 74% by weight acetaminophen and about 26% to 40% by weight of a copolymer that is cationic in character and is based on dimethylaminoethyl methacrylate and neutral methacrylic acid
15 esters.
W09917742(to Elan Corporation PLC, filed on September 30, 1998) discloses use of cationic copolymers synthesized from dimethylaminoethyl methacrylate and neutral methacrylic acid esters in amounts significantly greater than the amount of drug in need of 20 taste masking to form with the drug a taste masked micromatrix powder.
WO027045445 (to Novartis AG, filed on October 17, 2006) discloses a dispersible tablet of deferasirox or its pharmaceutically acceptable salt present in an amount of 42% to 65% by weight of the tablet with conventional pharmaceutical excipients. The dispersible tablet of 25 high drug load can be manufactured by granulating the active without adding excipients other than binder and surfactant
WO2004035026 (to Novartis Pharma GMBH, filed on October 14, 2003) discloses a dispersible tablet of deferasirox or its pharmaceutically acceptable salt present in an amount 30 of 5% to 40% by weight of the tablet with conventional pharmaceutical excipients.

4 WO2005097062 (to Novartis Pharma GMBH, filed on April 7, 2005) also discloses a dispersible tablet of deferasirox or its pharmaceutically acceptable salt present in an amount of 42% to 65% by weight of the tablet with conventional pharmaceutical excipients. The dispersible tablet allows an oral dosage form having a drug load of 1 OOOmg. 5
The disclosure of all these patents and patent applications are herein incorporated by reference.
The processes used for taste masking in the prior art involve multiple steps which are 10 technically complicated and difficult to reproduce, besides being economically disadvantageous.
Therefore, there still exists a need for a palatable and taste masked dosage form having flexibility in dosage titrations especially for children and older people and to achieve a better 15 balance between taste masking and dissolution than the conventional forms.
Object of the Invention:
The object of the invention is to provide a oral dosage formulation for use in children and 20 other patients who have difficulty swallowing conventional solid forms.
Another object of the invention to provide a palatable oral formulation that provides immediate release of the active ingredient in the stomach.
25 Still another object of the present invention is to provide the said pharmaceutical composition with ease of manufacture.
Summary of the Invention:
30 According to one aspect of the present invention there is provided an oral pharmaceutical formulation comprising one or more active ingredients in combination with one or more

5 pharmaceutical adjuvants wherein the active ingredient(s) is coated with water soluble polymer or combination of a water soluble and a water insoluble polymer
According to second aspect of the present invention, there is provided a taste masked 5 dispersible oral formulation comprising an iron chelator, such as deferasirox with one or more pharmaceutical adjuvants.
It will be appreciated that, where appropriate, the or each active ingredient employed in the present invention may be provided in the form of its pharmaceutically acceptable salt,
10 pharmaceutically acceptable solvate, pharmaceutically acceptable enantiomer, pharmaceutically acceptable derivative, pharmaceutically acceptable polymorph or pharmaceutically acceptable prodrug or combinations thereof. Thus, the iron chelator may be provided in the form of its pharmaceutically acceptable salt, pharmaceutically acceptable solvate, pharmaceutically acceptable enantiomer, pharmaceutically acceptable derivative,
15 pharmaceutically acceptable polymorph or pharmaceutically acceptable prodrug or combinations thereof. More specifically, deferasirox may be provided in the form of its pharmaceutically acceptable salt, pharmaceutically acceptable solvate, pharmaceutically acceptable enantiomer, pharmaceutically acceptable derivative, pharmaceutically acceptable polymorph or pharmaceutically acceptable prodrug or combinations thereof.
20
According to third aspect of the present invention, there is provided a taste masked sprinkle oral formulation (e.g. in the form of capsule or sachets) comprising an iron chelator, such as deferasirox with one or more pharmaceutical adjuvants.
25 According to fourth aspect of the present invention, there is provided a taste masked effervescent oral formulation (e.g. in the form of capsule, sachets, or effervescent tablet) comprising an iron chelator, such as deferasirox with one or more pharmaceutical adjuvants.
According to fifth aspect of the present invention, there is provided a taste masked 30 dispersible oral formulation (e.g. in the form of capsule, sachets or dispersible tablet) comprising an iron chelator, such as deferasirox with one or more pharmaceutical adjuvants.

6 According to sixth aspect of the present invention, there is provided a process for manufacturing the said taste masked oral pharmaceutical formulation.
According to another aspect of the invention there is provided an oral pharmaceutical 5 formulation comprising an iron chelator in combination with one or more pharmaceutical adjuvants, wherein the iron chelator, or combination of the iron chelator and the or each adjuvant, is coated with water soluble polymer or combination of a water soluble and a water insoluble polymer. Preferably the iron chelator alone is coated with the polymer (i.e. the adjuvants are not coated with the polymer).
10
It is a particularly preferred feature of the invention that the oral dosage form is an immediate release formulation. This means that the active material (especially the iron chelator, particularly deferasirox) will be released in the stomach, and will not remain unavailable until later. In an embodiment, the formulation is such that not less than 75 wt%, preferably not less
15 than 80 wt%, of the active dissolves within 30 minutes of administration.
Detailed description of the Invention:
20 As discussed hereinbefore, there is a continuing need for a palatable and taste masked dosage form having flexibility in dosage titrations, especially for children and geriatric people and to achieve a better balance between taste masking and dissolution than the conventional forms.
The present inventors have surprisingly found that coating one or more actives with a water 25 soluble polymer or a combination of a water insoluble and a water soluble polymer provides taste-masked characteristics without causing delay of drug release when combined in accordance with this invention.
The water soluble polymers that may be used in the coating may comprise homopolymers 30 and co-polymers of N-vinyl lactams, especially homopolymers and co-polymers of N-vinyl pyrrolidone e.g. polyvinylpyrrolidone (PVP), co-polymers of PVP and vinyl acetate, copolymers of N-vinyl pyrrolidone and vinyl acetate or vinyl propionate; cellulose derivatives

7 such as methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, methyl hydroxyethyl cellulose, hydroxypropyl methyl cellulose; high molecular polyalkylene oxides such as polyethylene oxide and polypropylene oxide and co-polymers of ethylene oxide and propylene oxide or mixtures thereof. 5
When present, suitable water insoluble polymers include acrylic copolymers e.g. Eudragit El00 or Eudragit EPO; Eudragit L30D-55, Eudragit FS30D, Eudragit RL30D, Eudragit RS30D, Eudragit NE30D, Acryl-Eze (Colorcon Co.); polyvinyl acetate, for example, Kollicoat SR 30D (BASF Co.); cellulose derivatives such as ethyl cellulose, cellulose 10 acetate, carboxypolymethylene, hydrxpropyl methylcellulose, hydroxypropyl cellulose, hydroxypropyl ethylcellulose, hydroxyethylcellulose, methylcellulose, e.g. Surelease (Colorcon Co.), Aquacoat ECD and Aquacoat CPD (FMC Co.) or mixtures thereof.
Children, geriatric patients, and many other people have difficulty in swallowing 15 conventional tablets and/or capsules. Therefore, it is often desirable to provide the drug either in liquid form or a convenient solid dosage form. Even where the drug can be formulated as a liquid, it is desirable to provide an oral dosage form such as sprinkled forms for eg. powders, pellets, granules, microspheres that can be incorporated in capsules or sachets; mouth dissolving tablets; dispersible tablets; effervescent tablets as these are more convenient and 20 easier to administer.
Due to its ease in administration and pleasant taste, it helps to encourage patients to adhere to daily medication regimens and therefore provides better compliance. These dosage forms combine the advantages of both liquid and conventional tablet formulations, and also offer 25 advantage over both traditional dosage forms. It further allows the luxury of much more accurate dosing than the primary alternative, oral liquids.
According to the present invention, the taste of an active ingredient can be masked by coating an active ingredient with a water soluble polymer or water soluble-water insoluble polymer 30 combination.

8 Not limiting the scope of the invention, the oral composition may comprise of one or more active pharmaceutical ingredients from therapeutic categories of H2 receptor antagonists, antibiotics, analgesics, cardiovascular agents, peptides or proteins, hormones, anti-migraine agents, anti-coagulant agents, iron-chelating agents, anti-emetic agents, anti-hypertensive 5 agents, narcotic antagonists, chelating agents, anti-anginal agents, chemotherapy agents, sedatives, anti-neoplasties, prostaglandins, drugs for erectile dysfunction, drugs acting on central nervous system, anti-diarrhoeal, antidiuretic agents or any other drug for which rapid dissolution, taste masking, palatability, consistent bioavailability and administration convenience is desired.
10
Exemplary bitter or unpleasant tasting drugs that may be envisaged within the scope of this invention includes, for example, cimetidine, enalapril, lorazepam, zolmitriptan, domperidon, selegiline, etinidine, ondansetron, lupitidine, famotidine, nizatidine, deferasirox, mirtazepine, hyosyamine sulphate, risperidone, citalopram, olanzapine, ranitidine, rizatriptan, piroxicam,
15 desloratadine, cetirizine, loperamide, sildenafil, topiramate, nifentidine, niperotidine, roxatidine, sulfotidine, tuvatidine and zaltidine; antibiotics, such as penicillin, ampicillin and erythromycin, acetaminophen; caffeine, dextromethorphan, diphenhydramine, theophylline, spironolactone and chlorpheniramine and pharmaceutically acceptable salts or derivatives thereof. The above drugs are not limiting but merely exemplary of unpleasant tasting drugs
20 that may be employed in this invention.
One particularly preferred class of drugs are the iron chelators, of which deferasirox is a preferred example.
25 According to the present invention, the oral pharmaceutical formulation may be in the form of "sprinkle" formulations (for eg. powders, pellets, granules, microspheres that can be incorporated in capsules or sachets); mouth dissolving tablets; dispersible tablets; effervescent tablets; chewable tablets. Preferably the oral dosage form according to the present invention is in the form of sprinkle capsule & dispersible tablets.
30

9
According to one embodiment, the oral pharmaceutical formulation according to the present invention may be a dispersible tablet comprising an iron chelator, such as deferasirox with one or more pharmaceutical adjuvants.
5 According to the above aspect, the dispersible oral formulation of the present invention comprises an iron chelator, such as deferasirox coated with one or more water soluble polymers or a mixture of one or more water soluble and one or more water insoluble polymers with one or more pharmaceutical adjuvants.
10 According to another embodiment, the oral pharmaceutical formulation according to the present invention may be a sprinkle oral formulation comprising an iron chelator, such as deferasirox with one or more pharmaceutical adjuvants.
The sprinkle oral formulation according to the present invention may comprise an iron 15 chelator, such as deferasirox with one or more pharmaceutical adjuvants in the form of powder admixture, granules, pellets, microcapsules, minitablets that are directly administered by "sprinkling the formulation with regular meals. Alternatively, it may be administered by incorporating into capsules or sachets and then administered through oral route.
20 In a preferred embodiment, the sprinkle oral formulation comprise of an iron chelator, such as deferasirox coated with one or more water soluble polymer or mixture of one or more water soluble & one or more water insoluble polymer; with one or more pharmaceutical adjuvants.
25 According to third embodiment, the oral pharmaceutical formulation according to the present invention may be an effervescent oral formulation comprising an iron chelator, such as deferasirox with one or more pharmaceutical adjuvants.
According to fourth embodiment, the oral pharmaceutical formulation according to the
30 present invention may be a chewable oral formulation comprising an iron chelator, such as
deferasirox coated with one or more water soluble polymers or mixture of one or more water

10 soluble and one or more water insoluble polymers with one or more pharmaceutical adjuvants.
According to present invention, the amount of the active ingredient is preferably in the range 5 of about 5% to 50% by weight of the formulation, more preferably in a range of about 10% to 48% by weight of the formulation.
The pharmaceutical adjuvants that may be present in the oral pharmaceutical formulations comprise one or more pharmaceutical adjuvants known to the person skilled in the art which 10 include, but are not limited to, diluents, binders, water soluble polymers, water insoluble polymers, sweeteners, flavors, fillers, disintegrants, surfactants, glidants, lubricants, preservatives, stabilizers.
Suitable diluents that may be used, according to the present invention, comprise calcium
15 phosphate-dibasic, calcium sulfate, cellulose-microcrystalline, cellulose powdered, dextrates, dextrins, dextrose excipients, fructose, lactitol, lactose, mannitol, sorbitol, starch, starch pregelatinized, sucrose, sugar compressible, sugar confectioners and equivalents thereof, or their mixtures. The amount of the diluent is preferably in the range of 10% to 70% by weight of the formulation.
20
The water soluble polymers that may be used, according to the present invention, comprise homopolymers and co-polymers of N-vinyl lactams, especially homopolymers and copolymers of N-vinyl pyrrolidone e.g. polyvinylpyrrolidone (PVP), co-polymers of PVP and vinyl acetate, co-polymers of N-vinyl pyrrolidone and vinyl acetate or vinyl propionate;
25 cellulose derivatives such as methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, methyl hydroxyethyl cellulose, hydroxypropyl methyl cellulose; high molecular polyalkylene oxides such as polyethylene oxide and polypropylene oxide and co-polymers of ethylene oxide and propylene oxide or mixtures thereof. The amount of the water soluble polymer is preferably in the range of 1% to 10% by weight of the
30 formulation.

11
The water insoluble polymers that may be used, according to the present invention, comprise acrylic copolymers e.g. Eudragit El00 or Eudragit EPO; Eudragit L30D-55, Eudragit FS30D, Eudragit RL30D, Eudragit RS30D, Eudragit NE30D, Acryl-Eze (Colorcon Co.); polyvinylacetate, for example, Kollicoat SR 30D (BASF Co.); cellulose derivatives such as 5 ethyl cellulose, cellulose acetate, carboxypolymethylene, hydrxpropyl methylcellulose, hydroxypropyl cellulose, hydroxypropyl ethylcellulose, hydroxyethylcellulose, methylcellulose, e.g. Surelease (Colorcon Co.), Aquacoat ECD and Aquacoat CPD (FMC Co.) or mixtures thereof. The amount of the water insoluble polymer is preferably in the range of 1 % to 10% by weight of the composition.
10
Plasticizers that may be used, according to the present invention, comprise sorbitan monolaurate (Span 20), sorbitan monopalmitate, sorbitan monostearate, sorbitan monoisostearate; citrate ester type plasticizers like triethyl citrate, citrate phthalate; propylene glycol; glycerin; low molecular weight polyethylene glycol; triacetin; dibutyl
15 sebacate, tributyl sebacate; dibutyltartrate, dibutyl phthalate or mixture thereof. The amount of the plasticizer is preferably in a range from 0% tol 0% by weight of the polymer.
Suitable binders that may be used, according to the present invention, comprise methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone 20 (e.g. PVP K30), gelatin, gum arabic, polyvinyl alcohol, pullulan, starch, pregelatinized starch, agar, tragacanth, sodium alginate, propylene glycol, alginate and other cellulose derivatives and equivalents thereof, or mixtures thereof. The amount of the binder is preferably in the range of 1% to 10% by weight of the formulation.
25 Suitable disintegrants that may be used, according to the present invention, comprise hydroxypropyl cellulose, carboxymethylcellulose, calcium carboxymethylcellulose, sodium carboxymethylcellulose, croscarmellose sodium, starch, crystalline cellulose, sodium starch glycollate, hydroxypropyl starch, partly pregelatinized starch, crospovidone and equivalents thereof, or mixtures thereof. The amount of the water soluble polymer is preferably in the
30 range of 5% to 30% by weight of the formulation.

12 If desired, a suitable surfactant may be used, for example, a nonionic surfactant, an anionic surfactant, a cationic surfactant, an amphoteric surfactant, or a mixture thereof. However, it is preferred that the oral dosage formulation according to the present invention does not contain any surfactant. 5
Suitable sweeteners that may be used, according to the present invention, comprise saccharides such as sucrose, dextrose, glucose, maltose, dextrins, D-tagatose, trehalose, dried invert sugar, fructose, levulose, galactose, com syrup solids, and the like, alone or in combination. Other examples of sweeteners comprise sodium saccharin; aspartame; sugarless 10 sweeteners including polyhydric alcohols such as sorbitol, mannitol, xylitol, glycerol, hydrogenated starch hydrolysates, maltitol, isomaltitol, erythritol, lactitol and the like, alone or in combination.
Suitable flavors that may be used, according to the present invention, comprise cinnamon, 15 wintergreen, eucalyptus, spearmint, peppermint, menthol, anise as well as fruit flavors such as apple, pear, peach, strawberry, cherry, apricot, orange, watermelon, banana and the like; bean-derived flavors, such as coffee, cocoa and the like or mixtures thereof,
Suitable lubricants/glidants that may be used, according to the present invention, comprise 20 stearic acid, esters & its derivatives like magnesium stearate, calcium stearate, zinc stearate,
sodium stearyl fumarate; talc; hydrogenated vegetable oil; sucrose esters of fatty acid;
microcrystalline wax; colloidal silicon dioxide and equivalents thereof, or mixtures thereof.
The amount of the lubricant/glidant is preferably in the range of 0.5% to 5% by weight of the
formulation. 25
Suitable preservatives mat may be used, especially in the sprinkle oral formulation, comprise
benzoic acid, sorbic acid, butylparaben, ethylparaben, methylparaben, propylparaben, sodium
benzoate, sodium propionate, or mixtures thereof.
30 Suitable stabilizers that may be used, especially in the sprinkle oral formulation, comprise alkali-metals and alkaline earth metals, bases of phosphates and organic acid salts and organic amines or mixtures thereof,

In addition to the conventional pharmaceutical adjuvants the effervescent oral formulations may comprise other adjuvants such as effervescent and non-effervescent disintegrants, edible organic acids. 5
The effervescent disintegrants that may be used in the effervescent oral formulation comprise alkali metal carbonates or alkali metal bicarbonates such as sodium bicarbonate, sodium carbonate, potassium bicarbonate and potassium carbonate, magnesium carbonate and sodium sesquicarbonate, sodium glycine carbonate, L-lysine carbonate, arginine carbonate 10 and amorphous calcium carbonate or mixtures thereof.
The non-effervescent disintegrants that may be used in the effervescent oral formulation comprise starches such as com starch, potato starch and modified starches thereof, sweeteners, clays, such as bentonite, macrocrystalline cellulose, alginates, gums such as agar, 15 guar, locust bean, karaya, pectin and tragacanth or mixtures thereof.
Additionally, the effervescent oral formulations may comprise organic acids, or their acidic salts such as citric acid, tartaric acid, malic acid, fumaric acid, adipic acid, and succinic acids, etc; acid anhydrides of the above described acids may also be used. Acid salts may include 20 sodium, dihydrogen phosphate, disodium dihydrogen pyrophosphate, acid citrate salts and sodium acid sulfite or mixtures thereof.
The oral pharmaceutical formulations according to the present invention can be manufactured by various techniques or processes known to the person skilled in the art including direct 25 compression, dry or wet granulation, fluidized bed granulation, melt extrusion, spray drying and solution evaporation, preferably the manufacturing process involves fluidized bed granulation technique.
The present invention further provides a process to manufacture the oral pharmaceutical 30 formulation, which process comprises-

14
(1) Coating one or more active pharmaceutical ingredients with one or more water soluble
polymers or a combination of one or more water soluble and water insoluble polymers to
form coated granules containing the active ingredient or ingredients,
(2) Mixing the coated granules obtained in step (1) with one or more pharmaceutical
5 adjuvants,
(3) Finally (i) filling the mixture formed in step (2) into capsules or sachets which can be
opened by a patient and its contents sprinkled onto food to ease administration; or (ii)
compressing the mixture formed in step (2) to form tablets which may alternatively be filled
into capsules or sachets.
10
In a particularly preferred embodiment the granules are coated with the polymer using the process of fluid bed granulation. According to this process, the granules are fluidised in a fluidisation chamber, using compressed air, which may be heated. The water soluble polymer(s), or the mixture of water soluble and water insoluble polymers, is sprayed over the
15 fluidised particles to coat them with the polymer.
We have found that using the fluid bed granulation technique according to the invention provides a particularly suitable method of coating active ingredients with the polymer, and makes it possible to satisfactorily coat products which have been difficult to taste mask in the 20 past, in particular iron chelators, such as deferasirox. We have found that the fluid bed granulation technique makes it possible to provide active ingredients with an immediate release profile, or taste masked formulation with polymer,
The following examples are for the purpose of illustration of the invention only and are not 25 intended in any way to limit the scope of the present invention.

Example 1:
Deferasirox Sprinkle capsule:

Sr. No. Ingredients Mg/Capsule
I Dry mix
1 Deferasirox 500.00
2 PVP K-30 40.00
3 Crospovidone 40.00
II Binder
4 PVP K-30 20.00
5 Purified water q. s.
III Lubrication
6 Mannitol 262.00
7 Crospovidone 120.00
8 Silicified Microcrystalline cellulose 200-00
9 Colloidal silicon dioxide 6.00
10 Sodium stearyl fumarate 12.00
Total 1200.00
5 Process:
(1) A dry mix of deferasirox, PVP K-30 and crospovidone was prepared.
(2) A binder solution was prepared by dissolving PVP K-30 in purified water until complete dissolution which was followed by wet granulating the dry mix and drying the granules.
(3) The granules obtained in (2) were blended with mannitol, crospovidone, silicified
10 microcrystalline cellulose and colloidal silicon dioxide lubricated with sodium stearyl
fumarate.
(4) The granules obtained in (3) were filled into capsules.
Example 2 15 Deferasirox Dispersible tablet:

Sr. No. Ingredients For 125 mg For 250 mg For 500 mg
Quantity/ tablet (mg) Quantity/ tablet (mg) Quantity/ tablet (mg)
Dry Mix
1 Deferasirox 125.00 250.00 500.00
2 PVPK30 10.00 20.00 40.00
3 Crospovidone 10.00 20.00 40.00
Binder
4 PVPK30 5.00 10.00 20.00
5 Purified water q.s. q.s. 18.00
Lubrication
6 Mannitol 62.50 125.00 250.00
7 Crospovidone 30.00 60.00 120.00
8 Silicified Microcrystalline cellulose 50.00 100.00 200.00
9 Colloidal silicon dioxide 1.50 3.00 6.00
10 Sodium stearyl fumarate 6.00 12.00 24.00
Total 300.00 600.00 1200.00
Process:
(1) A dry mix of deferasirox, PVP K-30 and crospovidone was prepared.
(2) A binder solution was prepared by dissolving PVP K-30 in purified water until complete 5 dissolution which was followed by wet granulating the dry mix and drying the granules.
(3) The granules obtained in (2) were blended with mannitol, crospovidone, silicified
microcrystalline cellulose and colloidal silicon dioxide lubricated with sodium stearyl
fumarate.
(4) The granules obtained in (3) were then compressed into tablets.
10

Example 3
Deferasirox Effervescent tablet:

Sr. No. Ingredients Quantity
< nig/tab)
Dry Mix
I Deferasirox 125.00
2 PVPK30 10.00
3 Crospovidone 10.00
Binder
4 PVP K30 5.00
5 Purified water q.s.
Lubrication
6 Mannitol 62.50
7 Crospovidone 30.00
8 Silicified Microcrystalline cellulose 50.00
9 Citric acid anhydrous 75.00
10 Sodium hydrogen carbonate 125.00
10 Colloidal silicon dioxide 1.50
11 Sodium stearyl fumarate 6.00
Total 500.00
5 Process:
(a) Dry mix blend of deferasirox, PVP K 30 & Crospovidone was prepared. (b)Granulating the above blend with solution of PVP K 30 in purified water.
(c) Above granules are dried, milled and then blended with mannitol, silicified
microcrystalline cellulose, citric acid anhydrous, sodium hydrogen carbonate, colloidal
10 silicon dioxide for sufficient time.
(d) Granules obtained in (3) were then blended with magnesium stearate and compressed into
tablets.

18 It will be readily apparent to one skilled in the art that varying substitutions and modifications may be made to the invention disclosed herein without departing from the spirit of the invention. Thus, it should be understood that although the present invention has been specifically disclosed by the preferred embodiments and optional features, modification 5 and variation of the concepts herein disclosed may be resorted to by those skilled in the art, and such modifications and variations are considered to be falling within the scope of the invention.
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. The use of "including," "comprising," or 10 "having" and variations thereof herein is meant to encompass the items listed thereafter and equivalents thereof as well as additional items.
It must be noted that, as used in this specification and the appended claims, the singular forms "a," "an" and "the" include plural references unless the context clearly dictates 15 otherwise. Thus, for example, reference to "a polymer" includes a single polymer as well as two or more different polymers; reference to a "plasticizer" refers to a single plasticizer or to combinations of two or more plasticizer, and the like.

19 CLAIMS:
1. An oral dosage formulation comprising a pharmaceutically active ingredient in
combination with one or more pharmaceutical adjuvants, wherein the active ingredient, or
5 combination of the active ingredient and the or each adjuvant, is coated with water soluble polymer or combination of water soluble and water insoluble polymer.
2. An oral dosage formulation according to claim 1, wherein the active ingredient is
selected from the therapeutic categories of H2 receptor antagonists, antibiotics, analgesics,
10 cardiovascular agents, peptides or proteins, hormones, anti-migraine agents, anti-coagulant agents, iron-chelating agents, anti-emetic agents, anti-hypertensive agents, narcotic antagonists, chelating agents, anti-anginal agents, chemotherapy agents, sedatives, antineoplastics, prostaglandins, drugs for erectile dysfunction, drugs acting on central nervous system, anti-diarrhoeal, antidiuretic agents.
15
3. An oral dosage formulation according to claim 2, wherein the active ingredient is an
iron chelator,
A. An oral dosage formulation according to claim 3, wherein the iron chelator is 20 deferasirox.
5. An oral dosage formulation according to claim 1, 2, 3 or 4, which is provided in the form of a sprinkle oral formulation.
25 6. An oral dosage formulation according to claim 1, 2, 3 or 4, which is provided in the form of an effervescent formulation.
7. An oral dosage formulation according to claim 1, 2, 3 or 4, which is provided in the
form of a dispersible tablet formulation.
30
8. An oral dosage formulation according to claim 1, 2, 3 or 4, which is provided in the
form of a chewable tablet formulation.

9. An oral dosage formulation according to any preceding claim, wherein the water
soluble polymer is selected from homopolymers and co-polymers of N-vinyl lactams,
especially homopolymers and co-polymers of N-vinyl pyrrolidone; co-polymers of PVP and
5 vinyl acetate; co-polymers of N-vinyl pyrrolidone and vinyl acetate or vinyl propionate; cellulose derivatives such as methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, methyl hydroxyethyl cellulose, hydroxypropyl methyl cellulose; polyalkylene oxides such as polyethylene oxide and polypropylene oxide and copolymers of ethylene oxide and propylene oxide; or mixtures thereof. 10
10. An oral dosage formulation according to any preceding claim, wherein the water
insoluble polymer is selected from comprise acrylic copolymers; polyvinylacetate; cellulose
derivatives such as ethyl cellulose, cellulose acetate, carboxypolymethylene, hydroxypropyl
methylcellulose, hydroxypropyl cellulose, hydroxypropyl ethylcellulose,
15 hydroxyethylcellulose, methylcellulose; or mixtures thereof.
11. An oral dosage formulation according to any preceding claim, wherein
pharmaceutical adjuvant may be selected from diluents, binders, water soluble polymers,
water insoluble polymers, sweeteners, flavors, fillers, disintegrants, glidants, lubricants,
20 preservatives, stabilizers.
12. An oral dosage formulation according to any preceding claim which does not contain
any surfactant.
25 13. An oral dosage formulation according to any preceding claim which is an immediate release oral dosage formulation.
14. A method of making an oral dosage formulation as defined in any preceding claim, comprising: 30 (1) Coating an active ingredient with one or more water soluble polymers or a combination of one or more water soluble and water insoluble polymers to form coated granules containing the active ingredient,

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(2) Mixing the coated granules obtained in step (1) with one or more pharmaceutical adjuvants,
(3) Processing the mixture formed in step (2) to form the desired oral dosage formulation.
5 15. A method according to claim 14, wherein the active ingredient is coated with the polymer by fluidising particle of the active ingredient, and spraying the polymer over the fluidised active ingredient, until the active ingredient becomes coated with the polymer.
16. A method according to claim 14 or 15, wherein the step (3) comprises filling the
10 mixture formed in step (2) into capsules or sachets to form a sprinkle formulation
17. A method according to claim 14 or 15, wherein step (3) comprises compressing the
mixture formed in step (2) to form tablets.
15 18. A method according to claim 17, wherein said tablets are dispersible, effervescent or chewable tablets.
19. A method according to claim 17, wherein the tablets are filled into capsules or
sachets.
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20. Use of a coating of a water soluble polymer, or a mixture of a water soluble and water
insoluble polymer to mask the taste of an active ingredient in an oral dosage formulation.
21. Use according to claim 20, wherein the active ingredient is deferasirox.
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22. An oral dosage formulation substantially as herein described and illustrated with
examples.