FORM 2
THE PATENT ACT 1970
(39 of 1970)
&
The Patents Rules, 2003
PROVISIONAL SPECIFICATION
(See section 10 and rule l3)
1. TITLE OF THE INVENTION:
"PHARMACEUTICAL FORMULATIONS"
2. APPLICANT:
(a) NAME: CIPLA LTD.
(b)NATIONALITY: Indian Company incorporated under the Indian Companies ACT, 1956
(c) ADDRESS: 289, Bellasis Road, Mumbai Central, Mumbai - 400 008, Maharashtra, India
3. PREAMBLE TO THE DESCRIPTION:
The following specification describes the invention.

Technical Field:
The present invention provides a convenient oral dosage formulation of active pharmaceutical ingredient and process for producing the said formulation thereof.
Background and Prior Art:
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 intended for adults who can easily swallow large tablets whole, the often disagreeable taste of the active ingredient need not be taken into account in formulating the medicine, except for the provision of means to prevent the taste from being apparent during the short time that 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 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 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 be difficult, if not impossible, to identify 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 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 chemicals mediating, flavoring or sweetening ingredients to the composition, which thereby mask the bitterness of the drug. When simple approaches 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.
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 hydroxypropyl cellulose or other cellulose derivatives to provide chewable taste-masked products. These prior art products, however, suffer from the disadvantage that the polymer coating releases the active agent in an inconsistent fashion and may not provide immediate release.
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.
EP0650353 discloses medicament cores coated with methacrylate ester copolymers which mask the bitter and unpleasant taste of the medicament.
US5275823 discloses a chewable tablet that includes granulate of a histamine H2-receptor antagonist and Eudragit ElOO, and an admixture of a taste-masking extragranuiar water-insoluble hygroscopic excipient.
EP0523847 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.


US4708867 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.
US4760093 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 esters.
W09917742 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 taste masking to form with the drug a taste masked micromatrix powder.
The processes used for taste masking in the patents listed above involve multiple steps which are 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 consistent bioavailability, flexibility in dosage titrations especially for children and older people and to achieve a better balance between taste masking, dissolution and rate of bioavailability than the conventional forms.
Object of the Invention:
The object of the invention to provide a stable convenient oral dosage formulation for use in children and other patients who have difficulty swallowing conventional solid forms.
Another object of the invention to provide a palatable convenient oral formulation that provides immediate release of the active ingredient in the stomach.


Yet another object of the present invention is to provide a taste-masked pharmaceutical formulation capable of incorporating one or more drugs.
Still another object of the present invention is to provide the said pharmaceutical composition with ease of manufacture.
Summary of the Invention:
According to one aspect of the present invention there is provided a convenient oral pharmaceutical formulation comprising one or more pharmaceutical active ingredient selected from H2 receptor antagonists, antibiotics, analgesics, cardiovascular agents, peptides or proteins, hormones, anti-migraine agents, anti-coagulant agents, anti-emetic agents, anti-hypertensive agents, narcotic antagonists, chelating agents, anti-anginal agents, chemotherapeutic agents, sedatives, anti-neoplastics, prostaglandins, drugs for erectile dysfunction, drugs acting on central nervous system, anti-diarrhoeal and antidiuretic agents in combination with one or more pharmaceutical adjuvants wherein the said one or more actives are coated with water soluble polymer or combination of water soluble & water insoluble polymer which assists balance between the dissolution and rate of bioavailability thereby masking bitter taste of the said one or more drugs.
According to second aspect of the present invention, there is provided a taste masked dispersible oral formulation comprising an iron chelator (e.g. deferasirox) or its pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable enantiomers, pharmaceutically acceptable derivatives, pharmaceutically acceptable polymorphs or pharmaceutically acceptable prodrugs or combination with one or more bitter drugs; with one or more pharmaceutical adjuvants representing immediate release profile.
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 (e.g. deferasirox) or its pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable enantiomers, pharmaceutically acceptable derivatives, pharmaceutically acceptable polymorphs or pharmaceutically


acceptable prodrugs or combination with one or more bitter drugs; with one or more pharmaceutical adjuvants representing immediate release profile.
According to fourth aspect of the present invention, there is provided a taste masked effervescent oral formulation (e.g. in the form of capsule or sachets) comprising an iron chelator (e.g. deferasirox) or its pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable enantiomers, pharmaceutically acceptable derivatives, pharmaceutically acceptable polymorphs or pharmaceutically acceptable prodrugs or combination with one or more bitter drugs; with one or more pharmaceutical adjuvants representing immediate release profile.
According to fifth aspect of the present invention, there is provided a process for manufacturing the said taste masked oral pharmaceutical formulation.
Detailed description of the Invention:
As discussed above and hereinafter, the inventor have surprisingly found that the incorporation of a polymeric coating of one or more actives with adequate amounts of water soluble polymer or combination of water insoluble & water soluble polymer thereby forming a drug-polymer porous complex provides superior elastic and taste-masked characteristics without causing delay of drug release when combined in accordance with this invention.
Children, elder persons, and many other people have difficulty swallowing conventional tablets and/or capsules. Therefore, it is often desirable to provide the drug either in liquid form or a convenient solid dosage form e. g„ small particles which can be sprinkled onto regular food and swallowed intact with the food, in contrast to the tablet or capsule intended to be swallowed as a whole. Even where the drug can be formulated as a liquid, it is desirable to provide a convenient oral dosage form or an alternative oral dosage form such as sprinkled forms such as powders, pellets, granules, microspheres that can be incorporated in capsules or sachets; mouth dissolving tablets; dispersible tablets; effervescent tablets as this becomes more convenient and easier to administer.


Due to their ease of administration and pleasant taste, they may encourage patients to adhere to daily medication regimens and therefore provide better compliance. These dosage forms combine the advantages of both liquid and conventional tablet formulations, and also offer advantage over both traditional dosage forms. They further allow the luxury of much more accurate dosing than the primary alternative, oral liquids.
Alternatively, the taste of an active ingredient can be masked by admixing an active ingredient and a pharmaceutically acceptable copolymer wherein the copolymer comprises water soluble-water insoluble polymer combination; and a solvent and then removing the solvent to yield a drug-polymer matrix which is porous in nature. This matrix formed is readily distinguished from a product comprising an active ingredient enterically coated with a copolymer by the fact that at a pH of less than 4, the drug polymer matrix releases the active ingredient wherein an enterically coated active ingredient will only be significantly released in an alkaline media.
According to the present invention, the convenient oral pharmaceutical form or an alternative oral dosage form may be in the form of "sprinkle" formulations such as powders, pellets, granules, microspheres that can be incorporated in capsules or sachets; mouth dissolving tablets; dispersible tablets; effervescent tablets: chewable tablets.
According to one embodiment, the oral pharmaceutical formulation according to the present invention may be a dispersible tablet comprising an iron chelator (e.g. Deferasirox) or its pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable enantiomers. pharmaceutically acceptable derivatives, pharmaceutically acceptable polymorphs or pharmaceutically acceptable prodrugs or combination with one or more bitter drugs; with one or more pharmaceutical adjuvants.
According to the above aspect, the dispersible oral formulation of the present invention comprise of an iron chelator (e.g. Deferasirox) or its pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable enantiomers, pharmaceutically acceptable derivatives, pharmaceutically acceptable polymorphs or pharmaceutically acceptable prodrugs or combination with one or more bitter drugs; with


one or more pharmaceutical adjuvants that may be processed by conventional means as known to a person skilled in the art.
In a preferred embodiment, the dispersible oral formulation comprise one or more pharmaceutical adjuvants known to the person skilled in the art which includes, but not limited to diluents, binders, water soluble polymers, water insoluble polymers, sweeteners, flavors, fillers, disintegrants, surfactants, glidants. lubricants.
Suitable diluents that can be used, according to the present invention, comprise of calcium 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, and/or mixtures thereof.
The water soluble polymers that can be used, according to the present invention, comprises of homopolymers 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, 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: high molecular polyalkylene oxides such as polyethylene oxide and polypropylene oxide and co-polymers of ethylene oxide and propylene oxide and/or mixtures thereof.
The water insoluble polymer that can be used, according to the present invention, comprises of acrylic copolymers e.g. F.udragit F. 100 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 ethyl cellulose, cellulose acetate e.g. Surelease (Colorcon Co.), Aquacoat ECD and Aquacoat CPD (FMC Co.) and/or mixtures thereof.
Additionally, plasticizers that can be used, according to the present invention, comprises


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 sebacate, tributyl sebacate; dibutyltartrate. dibutyl phthalate an/or mixture thereof.
Suitable binders that can be used, according to the present invention, comprise of methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone (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, and/or mixtures thereof.
Suitable disintegrants that can be used, according to the present invention, comprise of hydroxypropyl cellulose, carboxymethylcellulose. calcium carboxymethylcellulose, sodium carboxymethylcellulose, croscarmellose sodium, starch, crystalline cellulose, sodium starch glycollate, hydroxypropyl starch, partly pregelatinized starch, crospovidone and equivalents thereof, and/or mixtures thereof.
Suitable surfactant that can be used, according to the present invention, comprise of nonionic surfactant, an anionic surfactant, a cationic surfactant, an amphoteric surfactant or mixtures thereof. While not intended to limit the scope of invention, examples of surfactants include lauryl alcohols or lauryl ethers, for example, Brij 30; alkoxylated fatty alcohols, for example, PLURAFAC LF 120; block copolymers of EO/PO, for example, PLURONIC PE 10100 and SYNPERON1C PE/P84: alkylphenoxy polyethoxyethanols, for example, TRITON X-100; Polysorbates. for example, Tween 20, Tween 40, Tween 60, Tween 80, Tween 85; Polyoxyethylene esters, for example Span 20, Span 40, Span 60, Span 80; polyalkoxylated alkyphenols, for example. WITCONOL NS 108 LQ; dialkylphenol ethoxylates, for example, IGEPAL DM.
Suitable sweeteners that can be used, according to the present invention, comprise of saccharides such as sucrose, dextrose, glucose, maltose, dextrins, D-tagatose, trehalose, dried invert sugar, fructose, levulose, galactose, corn syrup solids, and the like, alone or in combination. Other examples of sweeteners comprise sodium saccharin; aspartame; sugarless 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 can be used, according to the present invention, comprise of cinnamon, 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 and/or mixtures thereof.
Suitable lubricants/glidants that can be used, according to the present invention, comprise of 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, and/or mixtures thereof.
According to the present invention, there is provided a process of making the said dispersible oral formulation comprising:
(1) Forming a mixture of an active ingredient and a matrix including a water soluble polymer or combination of water soluble-water insoluble polymer.
(2) Admixing the above matrix with compression filler, other adjuvants and a lubricant,
to form a plurality of compressed, rapidly disintegrate dosage forms including the active ingredient distributed in the orally dissolvable matrix, and alternatively coating the said dosage form with ready colour mix systems.
Alternatively, the formulation according to the present invention can be manufactured through various techniques or processes including direct compression, dry/wet granulation, melt extrusion, spray drying and solution evaporation.
According to second embodiment, the oral pharmaceutical formulation according to the present invention may be a sprinkle oral formulation comprising an iron chelator (e.g. Deferasirox) or its pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable enantiomers, pharmaceutically acceptable derivatives, pharmaceutically acceptable polymorphs or pharmaceutically acceptable


prodrugs or combination with one or more bitter drugs; with one or more pharmaceutical adjuvants.
The sprinkle oral formulation according to the present invention may comprise an iron chelator (e.g. Deferasirox) or its pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable enantiomers, pharmaceutically acceptable derivatives, pharmaceutically acceptable polymorphs or pharmaceutically acceptable prodrugs or combination with one or more bitter drugs; 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, they may be administered by incorporating into capsules or sachets and then administered through oral route.
In a preferred embodiment, the sprinkle oral formulation comprise of an iron chelator (e.g. Deferasirox) or its pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable enantiomers. pharmaceutically acceptable derivatives, pharmaceutically acceptable polymorphs or pharmaceutically acceptable prodrugs or combination with one or more bitter drugs; with one or more pharmaceutical adjuvants known to the person skilled in the art which includes, but not limited to diluents, binders, disintegrants, water soluble polymers, water insoluble polymers, coloring agents, flavoring agents, stabilizers, surfactants, lubricants, glidants, plasticizers and preservatives.
In a preferred embodiment, the sprinkle oral formulation comprise of an iron chelator (e.g. Deferasirox) or its pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable enantiomers. pharmaceutically acceptable derivatives, pharmaceutically acceptable polymorphs or pharmaceutically acceptable prodrugs or combination with one or more bitter drugs: with one or more pharmaceutical adjuvants which are coated with one or more water soluble polymer or mixture of one or more water soluble & one or more water insoluble polymer wherein the formulation may further comprise pharmaceutical adjuvants which include diluents, binders, disintegrants, coloring agents, flavoring agents, surfactants, lubricants, glidants & examples of which are embodied as above.


Additionally, plasticizers that can be used, according to the present invention, comprises 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 sebacate, tributyl sebacate: dibutyltartrate. dibutyl phthalate an/or mixture therof.
Additionally, preservatives that can be used, according to the present invention, comprises benzoic acid, sorbic acid, butylparaben, ethylparaben, methylparaben, propylparaben, sodium benzoate, sodium propionate, and/or mixtures thereof.
Additionally, stabilizers that can be used, according to the present invention, comprises alkali-metals and alkaline earth metals, bases of phosphates and organic acid salts and organic amines and/or mixtures thereof.
The water soluble polymers that can be used, according to the present invention, comprises of homopolymers 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, 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; high molecular polyalkylene oxides such as polyethylene oxide and polypropylene oxide and co-polymers of ethylene oxide and propylene oxide and/or mixtures thereof.
The water insoluble polymer that can be used, according to the present invention, comprises of acrylic copolymers e.g. Eudragit El 00 or Eudragit EPO; Eudragit L30D-55, Eudragit FS30D. Eudragit RL30D, Eudragit RS30D. Eudragit NE30D, Acryl-Eze (Colorcon Co.); polyvinylacetalc. for example. Kollicoat SR 30D (BASF Co.); cellulose derivatives such as ethylcellulosc. cellulose acetate e.g. Surelease (Colorcon Co.), Aquacoat ECD and Aquacoat CPD (FMC Co.) and/or mixtures thereof.
According to the present invention, there is provided a process of making the said sprinkle oral formulation comprising:


(1) Core particles were processed comprising one or more active pharmaceutical
ingredients with one or more water soluble polymers (preferably hydroxypropyl methyl
cellulose) and / or in combination with one or more water insoluble polymer (preferably
Eudragit grades) to form drug polymer coat matrix.
(2) The core particles obtained in step (1) were then finally mixed with one or more
pharmaceutical adjuvants such as diluents, binders, plasticizers, disintegrants. glidants,
lubricants, sweeteners or flavours which are finally filled into capsules or sachets which
can be opened by a patient and its contents sprinkled onto food to ease administration.
Alternatively, the formulation according to the present invention can be manufactured through various techniques or processes including direct compression, dry/wet granulation, melt extrusion, spray drying and solution evaporation.
According to third embodiment, the oral pharmaceutical formulation according to the present invention may be an effervescent oral formulation comprising an iron chelator (e.g. Deferasirox) or its pharmaceutical!) acceptable salts, pharmaceutical^ acceptable solvates, pharmaceutical!) acceptable enantiomers. pharmaceutical^ acceptable derivatives, pharmaceutical!) acceptable polymorphs or pharmaceutical^ acceptable prodrugs or combination with one or more bitter drugs; with one or more pharmaceutical adjuvants wherein the pharmaceutical adjuvants include, but not limited to flavors, diluents, colors, binders, filler, compaction vehicles, water soluble polymers, water insoluble polymers, examples of which are embodied as above.
Additionally, the effervescent disintegrants that can be used according to the present invention 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 and amorphous calcium carbonate and/or mixtures thereof.
Additionally, the non-effervescent disintegrants that can be used according to the present invention comprise starches such as corn starch, potato starch and modified starches thereof, sweeteners, clays, such as bentonite. microcrystalline cellulose, alginates, gums such as agar, guar, locust bean, karaya, pectin and tragacanth and/or mixtures thereof.


Additionally, the edible organic acids, or their acidic salts that can be used according to the present invention comprise food acids 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 sodium, dihydrogen phosphate, disodium dihydrogen pyrophosphate, acid citrate salts and sodium acid sulfite and/or mixtures thereof.
According to the present invention, there is provided a process of making the said effervescent oral formulation comprising:
(1) At least one active pharmaceutical ingredient mixed with other water soluble
adjuvants (e. g. water soluble polymer or combination of water soluble-water insoluble
polymer).
(2) Granules were prepared by using suitable granulating solvent,
(3) At least one effervescent or non-effervescent disintegrant and at least one edible organic acid were added and mixed with the granules prepared in step (2),
(4) Granules prepared in step (3) were mixed with rest of the adjuvants.
(5) Finally, the effervescent formulation of step (4) was either compressed in to tablets or filled into capsule or sachets.
Alternatively, the formulation according to the present invention can be manufactured through various techniques or processes including direct compression, dry/wet granulation, melt extrusion, spray drying and solution evaporation.
According to fourth embodiment, the oral pharmaceutical formulation according to the present invention may be a chewable oral formulation comprising an iron chelator (e.g. Deferasirox) or its pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable enantiomers. pharmaceutically acceptable derivatives, pharmaceutically acceptable polymorphs or pharmaceutically acceptable prodrugs or combination with one or more bitter drugs; with one or more pharmaceutical adjuvants.


The chewable oral formulation according to the above aspect may comprise pharmaceutical adjuvants known to the person skilled in the art are but not limited to fillers, diluents, sweeteners, flavors, binders, taste masking agents, water soluble polymers, water insoluble polymers, examples of which are embodied as above.
According to the present invention, there is provided a process of making the said chewable oral formulation comprising:
(1) Core particles were processed comprising one or more active pharmaceutical
ingredients with one or more water soluble polymers (preferably hydroxypropyl methyl
cellulose) and / or in combination with one or more water insoluble polymer (preferably
Eudragit grades) to form drug polymer coat matrix.
(2) The core particles obtained in step (1) were then finally mixed with one or more
pharmaceutical adjuvants such as diluents, binders, plasticizers, glidants, lubricants,
sweeteners or flavours which are finally compressed into tablets or alternatively filled
into capsules or sachets.
Alternatively, the formulation according to the present invention can be manufactured through various techniques or processes including direct compression, dry/wet granulation, melt extrusion, spray drying and solution evaporation.
Not limiting the scope of the invention, the oral pharmaceutical formulation 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, anti-emetic agents, antihypertensive 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, palatabiiity, consistent bioavailability and administration convenience is desired.
Exemplary bitter or unpleasant tasting drugs applicable thai may be envisaged within the scope of this invention includes, for example, cimetidine, enalapril, lorazepam, zolmitriptan, domperidon, selegiline, etinidine, ondansetron, lupitidine, famotidine,


nizatidine, mirtazepine, hyosyamine sulphate, risperidone, citalopram, olanzapine,
ranitidine, rizatriptan, piroxicam, desloratadine, cetirizine, loperamide, sildenafil,
topiramate, nifentidine. niperolidine, roxatidine. sulfotidine, tuvatidine and zaltidine;
antibiotics, such as penicillin, ampicillin and erythromycin, acetaminophen; caffeine,
dextromethorphan, diphenhydramine. theophylline, spironolactone and
chloropheniramine and pharmaceutically acceptable salts or derivatives thereof. The above drugs are not limiting but merely exemplary of unpleasant tasting drugs that may be employed in this invention.
The following example is for the purpose of illustration of the invention only and is not intended in any way to limit the scope of the present invention.

Sr. No. Ingredients Mg/Tab
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 Mannilol 262.00
7 Crospovidone 120.00
8 Silicified Microcrystalline cellulose 200.00
9 Aerosil 6.00
10 Sodium slearyl fumarate 12.00
Total 1200.00
Process:
(I) 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 microcrystalline cellulose and Aerosil lubricated with sodium stearyl fumarate.
(4) The granules obtained in (3) were compressed into tablets and finally coated.
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 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 "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 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.