TITLE:

Effective taste-masked chewable solid oral dosage form- Chewable tablet

FIELD OF THE INVENTION:

The present invention relates to a chewable solid oral formulation in the form of tablet comprising therapeutic compositions containing iron for oral use, and usually administered to people suffering from iron deficiency. The oral administration of therapeutic ferrous iron as the sulfate, citrate and Fumarate.etc, for use in treating iron deficiency anemia are well known. Of the various forms of ferrous salts, ferrous calcium citrate is generally preferred and well-tolerated. Chewable tablets are widely preferred for patients who have difficulty in swallowing conventional tablets or capsules. This invention pertains to a formulation process involving coating the active ingredients with suitable polymers for taste masking purpose and targeted release of the medicament.

OBJECTIVE OF THE INVENTION

Powders for reconstitution, suspensions, syrups, elixir solutions, along with conventional tablets are considered to be suitable dosage forms which satisfy the therapeutic need of the patients.
Conventional tablet is a simple pharmaceutical dosage form of tablet, comprising mixture of active ingredient and suitable excipients intended to therapeutically deliver a dose of active ingredient or group of active ingredients through oral route of administration. The tablets may be coated for environmental protection, and to make tablet smoother and easier to swallow. It is worth mentioning though, that some patients still find inconvenience in taking the liquid dosage forms, in measuring the exact dose accurately or in carrying the package along while traveling. The same problem is encountered with conventional tablets. All the mentioned reasons make chewable tablets one of the excellent alternative choices as an easy method of drug administration for these patients. Chewable tablets, regardless of their geometry, represent a particular form of oral dosage; they are intended to be chewed in the mouth by the patient and are not intended to be swallowed intact. Many chewable formulations are intended to be used to provide a known dosage of active to the people who either will refuse to swallow an intact tablet or have difficulty doing so. Such tablets are often used to administer analgesics, antacids, antibiotics, anticonvulsants, vitamins, multivitamins, minerals, multivitamin and mineral blends, and laxatives, by way of example. Because vitamins are generally unstable, however, finding a good tasting formula that is also stable has been difficult. Iron plays an important role in oxygen and electron transport. Symptoms of iron deficiency are fatigability; other symptoms of anemia include pallor, dyspnea on exertion, palpitation and a feeling of exhaustion.

When it comes to the needs of the anemic patients, Ferrous Calcium Citrate which is ferrous calcium salt of citric acid is a well-tolerated compound, and a hematinic used in treating iron deficiency anemia is a well-known compound having a chemical structure Folic acid (also known as folate, vitamin M, vitamin B9) chemically called as (2S)-2-[(4-{[(2-amino-4-hydroxypteridin-6-yl)methyl]amino}phenyl)formamido]pentanedioic acid, is a compound having the chemical structure It is especially important in aiding rapid cell division and growth, such as in infancy and pregnancy, and also protects against a number of congenital malformations, including neural tube defects. Ferrous calcium citrate is a tasteless drug, however giving a mild unpleasant metallic odor and folic acid is naturally a drug with that of bitter or unpleasant taste in mouth, Several patents propose several optimized formulations in the prior art which help in formulating an effective solid oral chewable formulation which is taste-masked in the form of tablet All the methods in the prior art focus mainly on the formulation and the process for developing an effective solid oral chewable tablets and for effective taste masking, but yet are complicated for manufacturing and does not display or display characteristics of mild palatability and mouth feel. Objectionable taste and/or mouthfeel continues to be a problem and make it less likely to obtain dosage compliance by the user. Palatability and "mouth feel" are among the most important characteristics to be considered in providing an effective chewable tablet formulation for an active medicament or nutritional supplement. Many bitter drugs give unpleasant taste and unacceptable mouth-feel due to the grittiness or chalkiness of the active moiety or their chemical nature. Despite these disclosures there is an ongoing need for a chewable tablet delivery system, that is pleasant tasting and provides improved mouth feel qualities. There is also an ongoing need for a chewable tablet delivery system that is pleasant tasting with acceptable mouth-feel, and possess a targeted release of drug into duodenum for enhancing absorption and also that is suitable for administration to persons having diabetes or hypoglycemia, and does not promote tooth decay or dental caries.

Hence there arises a need for developing a formulation which is reasonably economical for the process of making oral solid chewable tablets of especially which are taste-masking, gastro-resistant and provide palatability and effective mouth-feel. In the present embodiment, the objective of invention is to provide a novel formulation of Chewable dosage form in the form of tablet with effective taste masking of bitter drugs such as Ferrous calcium salt of citric acid and Folic acid. The formulation comprising multilayer polymer coating with an anionic Co-polymer preferably with Methacrylic acid copolymer and an cationic Copolymer preferably Methacrylate Copolymer in the form of dispersion or binder solution using a suitable solvent system.
It is another objective of the invention to provide a formulation of a chewable tablet which provides effective taste-masking, along with good palatability and mouth feel, comprising a combination of Mannitol, Maltodextrin and sorbitol. It is yet another objective of the invention to provide a formulation of stable tasteless therapeutic compound containing chemically bound calcium and iron in the ferrous state which upon oral administration are utilized normally without mutual interference between the calcium and iron and without gastro-intestinal disturbances, constipation or diarrhea. In addition to the foregoing, chewable tablets have several advantages that make them the method of choice in delivering certain types of therapeutic agents or actives to an even greater population. One such advantage is that certain types of tablets, because of the large size of the dosage, must be unusually large and, therefore, difficult to swallow. Furthermore, patient compliance with the prescribed therapy, such as antacid treatment, is enhanced by the use of smaller, more convenient tablets that may be consumed when it may be inconvenient to swallow pills.

In the present embodiment, it is the objective of the invention to provide a process of evaluating the improved properties such as taste masking and mouth feel, by various combinations and varying amount of ingredients. The in-vivo evaluation of taste of the formulation and enhanced mouth-feel property to impart "wet mouth feel" being done by the internal panel of 5 subjects selected randomly for a few a said formulations of chewable tablet. In the present invention Excipients used in the formulation such as diluents, binders, glidants and lubricants are also often added to make the tableting operation more effective, other excipients such as multi-layer coating polymers, when added to chewable tablets must not only be inert in respect of the active moiety, but also to provide taste masking. Other excipients such as sweeteners and flavors to preferably provide pleasant mouth feel and other excipients to prevent tooth packing, grittiness, and the like, without imparting any unpleasant characteristics to the tablets as they are chewed. Some excipients are added to enhance or retard the drug absorption rate, some are added to impart color. In some instances, excipients provide more than one benefit to the said finished chewable tablets The use of polyols such as mannitol, sorbitol, xylitol and lycasin, Nutritive sweeteners such as maltodextrin and maltose and non-saccharide sweetener such as aspartame, does not promote tooth decay and prevents dental caries, as they tend to maintain proper mineralization of tooth. Polyols such as mannitol and sorbitol are sugar alcohols derived from mono saccharides, and are not metabolized by cavity producing bacteria and hence they are non-cariogenic and maintain tooth mineralization./EFSA Journal 2011;9(4):2076)]. Sorbitol can sweeten saliva without causing a drop in the critical Salivary pH, which is usually altered by the bacterial fermentation. Maltodextrin, an oligosaccharide is found to have no potential for dental caries [Riva Touger-Decker and Cor van Loveren; Sugars and dental caries; Amen Jour. Clin. Nutr. October 2003 vol. 78 no. 4 881S-892S] Aspertame, non-saccharide sweetener does not cause dental caries and effectively safe for use. Aspertame. In a study on rat pups, inoculated with Streptococcus and fed basal diet with varying concentrations of sucrose and aspartame and aspartame alone.

The results displayed that sucrose with aspartame decreased caries formation, whereas the aspartame alone did not cause any caries formation [Sumitra Das, DDS, MS Arup K. Das, DDS, MD et. al; Aspartame and dental caries in the rat; PediatrDent 13:217-20, 1991] In the present embodiment of the invention, the active ingredient preferably chosen is Ferrous Calcium citrate, because of the unique character of Calcium in Ferrous calcium citrate, which has more affinity for the phosphates and phytates in the diet and form complexes with them to leave Ferrous Iron available for absorption, especially in the duodenum by the said targeted release of the dosage unit. In the particular aspect of the invention, the formulation is designed with an objective of first disintegrating the dosage unit into granules and particles within the neutral salivary pH of the mouth imparting initial pleasant mouth-feel and good palatability. This followed by gastro-resistant activity of the granules in stomach displaying active drug stability in the acidic pH, further allowing release of the drug in the duodenum at the pH above 5 by breaking up the enteric polymer coat, allowing complete absorption facilitating targeted release. In one particular aspect of the invention, the formulation, comprising Ferrous calcium citrate, which is well tolerated along with folic acid, may enhances the healing process of anemic patients by leaving more ferrous iron for absorption. The folic acid along with ferrous iron beneficially enhancing normal haemopoiesis.
The process in the present invention details about formulating an effective taste-masked chewable solid oral dosage form, in the form of tablet comprising active ingredients which are bitter drugs such as Ferrous Calcium Citrate and Folic acid, which impart an objectionable and unpleasant taste to the dosage form.

The dosage form is being coated with a composition involving the combination of anionic copolymer and a cationic copolymer for effective taste masking. Further the formulation incorporates the use of combination of diluents such as Mannitol, Maltodextrin and Sorbitol in various stages of granulation and pre-lubrication for providing good palatability, enhanced taste and better mouth feel. Finally the dosage form in the form of tablet is being coated with seal coating with Opaglos for moisture barrier over the tablet followed by film coating, comprising a sweetening agent and a flavoring agent. The granulation in the present invention is being carried out by the method of wet granulation separately for Ferrous calcium citrate and Folic acid along with selected suitable excipients before subjecting to Prelubrication by combining both the granulates, followed by the lubrication process, and subsequent seal coating and coating process
The overcoming of complexities in the present embodiment of the invention in the granulation stage for various parameters such as bulk density, tapped density, carr's compressibility index, Hausner"s ratio, and Loss on drying are optimized by subsequent changes in the excipient quantities during various stages of formulation to provide effective dosage unit of chewable tablet.
The process parameters in the present invention such as temperature, air pressure, drying time, pump rotations, flap positions, granulation time, mixing time and drying time, The dosage unit parameters like weight variation, uniformity of weight, thickness, length, width, hardness, friability, The coating parameters such as drying time, spraying rate, Pan RPM, air flow, pressure and distance between spray gun and tablet bed were overcome by monitoring and optimization of the above mentioned parameters. The technicality of the process in the present invention for the manufacturing of the chewable tablet for effective taste masking, and good palatability and mouth feel involves the coating of core granules of active drug by anionic and cationic copolymers which are pH dependent by multi-layer coating technology followed by addition of combination of diluents with ability to impart effective palatability and mouth feel, and other suitable excipients and subjecting to compression into tablet, further followed by seal coating and film coating comprising a sweetening and a flavoring agent.

The product pattern of active ingredient release in the embodiment of the invention, is designed with the objective of providing initially enhanced taste - masking effect on immediate disintegration in buccal cavity on chewing the dosage unit by the process of mastication, providing good palatability and enhanced mouth-feel property followed by gastro-resistant activity of the granules of active ingredient in the stomach pH, further facilitating complete iron absorption. The overall product providing means for targeted delivery in the duodenal part of the intestine. In the present embodiment, invention relates to an objective of formulating of chewable tablet to provide an overall product characteristic such as gastro-resistant activity, effective taste-masking, good palatability, enhanced mouth-feel effect and targeted release facilitating better iron absorption in the duodenum. The objective of taste-masking effect in the present embodiment of the invention is to be provided by the coating of the pH dependant cationic polymer, being coated on to the gastro-resistant granules of the said metallic ferrous calcium citrate in the said chewable dosage unit The objective of payability and mouth-feel in the present embodiment of the invention is to be provided by the combination of suitable, comprising polyols or sugar alcohols and a nutritive sweetener, further comprising acidifier, alkalizer in combination with sweetener, such as aspartame with flavoring agents such as mango, spearmint and menthol flavor, masking an characteristic taste of the said chewable dosage unit. The objective of the enhanced iron absorption in the present embodiment of the invention is to be provided by the coating of pH - dependent anionic copolymer, being coated on to the said metallic ferrous calcium citrate for targeted duodenal release from the chewable dosage unit.

NOVELTY:
The formulation in the present embodiment of the invention is itself a reasonable novel approach for obtaining a chewable tablet, more convenient in administration than a conventional tablet, especially imparting good palatability and wet-mouth feel property along with effective taste masking nature of the dosage unit. The formulation in the present embodiment of the invention in which the granules and particles of active substance are coated first with coating composition containing a gastro-resistant coat of a pH dependent anionic polymer preferably Methacrylic acid copolymer along with suitable excipients followed by coating with a pH dependent Cationic polymer preferably Methacrylate Copolymer, which imparts taste-masking effect. The formulation in the present invention which involves making the chewable tablet core with a novel combination of gastro-resistant & Taste-masked granules obtained by coating with cationic and anionic copolymers, comprising various diluents, such as sorbitol and mannitol in combination with other excipients such as acidulating agent, alkalizer, sweetening agent, flavoring agent, glidant and a lubricant followed by moisture barrier coating and a water soluble film coating with an oligosaccharide, sweetener and a flavor. The whole dosage unit comprising multi-layer particle coating technology The formulation in the present embodiment of the invention relates to a chewable dosage form which on disintegration from the said chewable tablet does not impart unpleasant taste or does not release the drug in the buccal cavity and is taste-masked, which is followed by the release of the active moiety in the duodenum enhancing the iron absorption, making the overall dosage unit as a targeted delivery system.

SUMMARY

In one embodiment, the present invention provides a formulation of chewable tablets, comprising coating with a pH dependent anionic copolymer and a cationic copolymer which are preferably included to impart gastro-resistant effective taste masking effect. In another embodiment of present invention relates to a novel formulation of chewable tablet with improved taste-masking effect and better palatability and enhanced mouth-feel property. More particularly the present invention provides a formulation of novel excipient base for a chewable tablet comprising excipients such as diluents like sorbitol, mannitol and Maltodextrin in combination with acidulating agent, alkalizer, sweetening agent, flavoring agent, glidant and a lubricant, wherein the novel excipient base provides for an improved taste, stabilization and effective mouth feel qualities.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to an oral pharmaceutical formulation of chewable tablet, comprising coating of active ingredients with a pH dependent anionic polymer and a pH dependent cationic polymer, preferably to impart gastro-resistant activity and effective taste masking effect. In an embodiment of the present invention relates to a formulation of chewable tablets with improved taste-masking effect and better mouth palatability and mouth-feel property. More particularly the present invention provides a novel formulation of excipient base for a chewable tablet comprising excipients such as diluents like sorbitol, mannitol and Maltodextrin in combination with acidulating agent, alkalizer, sweetening agent, flavoring agent, glidant and a lubricant, wherein the novel excipient base provides for an improved taste, stabilization and effective mouth feel qualities. The Present invention to provide a stable tasteless therapeutic compound containing chemically bound calcium and iron in the ferrous state which upon oral administration are utilized normally without mutual interference between the calcium and iron and without gastro-intestinal disturbances, constipation or diarrhea. The present invention provides a formulation of chewable tablet which have reduced or eliminated dry mouth feel and greatly reduced or eliminated tooth decay or dental caries In the present invention, the formulation provides an eliminated or reduced dry mouth feel by combination of sweetening diluents such as sorbitol and mannitol.which are not actual sugars, but their derivatives with that of sweetening agent such as aspartame. Incorporation of these excipients in the excipient base produces a sugar free or sugar less formulation available as chewable tablet, which on mastication and chewing eliminates the dry mouth feel by stimulating the production of saliva in the mouth, the salivary pH, further neutralized by a combination of acidifier and an alkalizer in the excipient base, providing an overall elimination of dry mouth feel by the said formulation.

The dry mouth feel can be usually eliminated by chewing sugar free gums or sugar-free chewable tablets. In the present invention, the formulation provides a reduced or eliminated tooth decay or dental caries by comprising excipients such as sorbitol, mannitol, which are polyols and maltodextrin, which is an oligosaccharide natural sweetener. The incorporation of polyols and the said oligosaccharide in the excipient base of the said formulation does not cause tooth decay or dental caries on oral administration and further maintains mineralization of the teeth. Usually tooth decay and dental caries are caused by acid being produced by fermentable sugars such as glucose, sucrose and fructose. The present invention provides a novel formulation of chewable tablets which have improved dosage qualities such as taste-masking and pleasant smell, enhanced palatability and effective mouth-feel, attractive shape and texture resembling mango fruit and improved iron absorption on targeted release in duodenum. Taste-masking is being provided by methacrylate polymer coating, pleasant smell is by combination of sweetening agent with different flavoring agents, mango fruit like attractive shape by suitable punches, texture by suitable film coating and enhanced iron absorption provided by methacrylic acid polymer coating.
In the present embodiment of the invention, the active ingredient preferably chosen for the chewable tabletis Ferrous Calcium salt of citric acid (ferrous calcium citrate), because of the unique character of Calcium in the said active ingredient, which has more affinity for the phosphates and phytates in the diet forming complexes with them to leave more amount of Ferrous Iron available for absorption, especially delivered in the duodenum by the said targeted release design of the dosage unit. As used herein the term "Palatability" refers to the property of the chewable tablet being acceptable in relation to taste and odor in the buccal cavity.

As used herein the term "Mouth-feel" refers to the interaction of the dosage unit with the mouth usually evaluated by perception through mastication and after-taste. Palatability and mouth-feel of a dosage unit, especially of a chewable tablet are provided usually by effective taste masking of bitter active ingredients by various pharmaceutical techniques, employed in the prior art such as addition of taste-masking excipients, microencapsulation, particle coating, film coating with suitable polymer, coated liquiflash particles and shear-form floss particles, coated roto-granules, use of sweeteners and flavors, ion-exchange resins and use of alternative metallic salts. In the present embodiment, the invention provides a process of evaluating the improved properties such as taste masking and mouth feel, by various combinations and varying amount of ingredients. The in-vivo evaluation of taste of the formulation and enhanced mouth-feel property to impart "wet mouth feel" being done by the internal panel of 5 subjects selected randomly for a few a said formulations of chewable tablet. As used herein the term "Wet Mouth" refers to the proper salivation and wetting of mouth on gradual stimulation of saliva in the buccal cavity. In the present embodiment of the invention, the "wet mouth feel" is provided by the formulation, comprising sugar alcohols such as sorbitol and mannitol, with combination of a sweetener, like aspartame, and some flavoring agents such as Spearmint, mango and menthol flavors which stimulates gradual salivation in the buccal cavity eliminating the dryness of the mouth. The wet mouth -feel further maintained by acidifier like citric acid and an alkalizer like sodium citrate which balances the neutral salivary pH. In the particular embodiment of the invention, the chewable formulation is designed with an objective of first allowing the dosage unit to disintegrate into granules and particles in the neutral salivary pH of the mouth imparting initial pleasant mouth-feel and enhanced palatability, obstructing release of active ingredient by taste-masking gastro-soluble coating, followed by gastro-resistant activity of the granules in stomach by enteric coating, displaying active drug stability in the acidic pH, further allowing release of the drug in the duodenum at the pH above 5 by breaking up the enteric polymer coat, allowing complete absorption of free ferrous iron form facilitating targeted release.

In the particular embodiment, the invention relates to the chewable formulation, comprising Ferrous calcium citrate, which is well tolerated along with folic acid, and devoid of complete toxicity, enhances the healing process of anemic patients by leaving more ferrous iron for absorption, leading to enhanced rise in hemoglobin and beneficially enhancing normal haemopoiesis. Further the formulation designed being well tolerated with no incidence of Nausea, and much lesser incidence of side effects such as flatulence, Diarrhea, constipation and absence of epi-gastric abdominal discomfort. The present invention also relates to the process of formulating chewable tablet with effective taste masking of bitter active ingredients which are selected to be an iron supplement mostly hematinic and a nutritional supplement. Preferably the bitter active ingredients are Ferrous calcium citrate (Hematinic) and Folic acid (Nutritional supplement) The present invention also relates to the process of evaluating the improved properties such as taste masking and mouth feel, by various combinations and varying amount of ingredients, the in-vivo evaluation of taste and enhanced mouth-feel property to impart wet mouth feel being done by the internal panel of 5 subjects selected randomly for a few selected formulations Employed in the art, in the present embodiment of the invention is formulation being made by Multilayer particle coating technology, comprising coating with Methacrylic acid Copolymer and a Methacrylate Copolymer, which is a derivative of neutral methacrylic acid and dimethylaminoethyl methacrylate esters, involving the use of Fluid Bed Processor.
The present invention also relates to theuse of other excipients such as diluents, binders, Acidulating agent, alkalizer, sweetening agent, flavoring agent, coloring agent, glidant and a lubricant.

The present invention also relates to barrier coating of the chewable tablets with a suitable seal coat for moisture barrier, and a film coating comprising a coating polymer, an oligosaccharide, a sweetener, a flavor, an opacifier and colourant dispersed in a mixture of suitable solvents. The polymers for multi-layer coating of the chewable tablets of the present invention are selected to be a combination of pH dependent Methacrylic acid Copolymer and a Methacrylate Copolymer, which is a derivative of dimethylaminoethyl methacrylate and neutral methacrylic acid esters,
Methacrylic acid Copolymer for the present invention is selected from a group of anionic copolymers, preferably based on Methyl acrylic acid and ethyl acrylate, intended to be preferably dispersible in water so as to take advantage of aqueous formulation techniques and has a rapid rate of dissolution at a pH of about 5.5. Methacrylic acid Copolymer most preferably used here is Methacrylic acid - Ethyl Acrylate Copolymer, commercially available as Eudragit L Grade, insoluble at a pH rage of 3-5, providing immediate release upon reaching the duodenum that have solubility above pH 5 and showing gastric - resistance in the stomach. Methacrylic acid Copolymer based on Methyl acrylic acid and ethyl acrylate, may have a structural formula such as Methacrylate Copolymer, for the present invention is selected from a group of cationic copolymers, which are derivatives of dimethylaminoethyl methacrylate and neutral methacrylic acid esters, and which are based on butylated methacrylate group intended to be water soluble via salt formation with acids, thus providing gastro-soluble film coatings, and providing taste masking effect in the neutral pH of saliva in the buccal cavity.

Methacrylate Copolymer, most preferably used here is basic butylated Methacrylate Copolymer, commercially available as Eudragit E Grade, swell and are permeable in water and buffer solutions above pH 5. It is soluble in gastric fluid below a pH of 5. The Cationic Methacrylate copolymer with a dimethylaminoethyl group preferably with butylated Methacrylate may have the following structural formula such as where: R1 = R3 = CH3 R2 - CH2CH2N(CH3)2 R= CH3, C4H9. The diluents used for the present invention is selected from a group of polyols such as sorbitol, mannitol, xylitol and lycasin which are sugar alcohols derived from monosaccharides and Nutritive sweeteners such as maltodextrin.maltose, maltilol dextrose and glucose. Most preferred polyols used here is Sorbitol and Mannitol. Sorbitol, also known as sugar alcohols can sweeten saliva without causing a drop in the critical salivary pH, which is usually altered by the bacterial fermentation. Mannitol, a sugar alcohol derived from mannose by reduction, does not cause dental caries and enhances the mouth-feel. Most preferred Nutritive sweetener used here is maltodextrin, which is an easily digestible non-sweet oligosaccharide, consisting of D-glucose units, have no effect on dental caries provides soft mouth-feel for the chewable tablet
Binders used for the present invention is selected from a group of excipients such as Microcrystalline cellulose, Hydroxypropyl cellulose, Hydroxyethyl cellulose, Hydroxy propyl Methyl cellulose and Polyvinylpyrrolidone. Most preferred binder used here is Polyvinyl Pyrrolidone, (Povidone - K 30), preferably as bry binder and preferably in combination with Shellac, which is used for providing moisture barrier, preferably with a suitable solvent such as Isopropyl Alcohol.
Acidulants used for the present invention is selected from a group of excipients such as citric acid, lactic acid, malic acid, adipic acid, benzoic acid, fumaric acid, preferably citric acid known for its pH-lowering nature and to impart flavor and preservative action.

Alkalizer used for the present invention is selected from the group of excipients such as sodium bicarbonate, sodium citrate, potassium citrate, calcium carbonate and calcium acetate, preferably sodium citrate, for raising the pH of saliva facilitating the taste masking nature of Cationic Methacrylate copolymer (Eudragit E grade). Disintegrants used for the present invention is selected from a group of excipients such as maize starch, sodium Carboxymethylcellulose, Calcium Carboxymethylcellulose, sodium starch glycolate, crospovidone, preferably sodium starch glycolate for swelling and breakdown of the chewable tablet into multiple large particles on mastication in mouth. Sweeteners used for the present invention are Non-saccharides such as Sucralose, Aspertame, Saccharin and Neotame. They are non-cariogenic and maintain tooth mineralization preventing dental caries, and are not metabolized by cavity producing bacteria, which usually produce acid by fermentable sugars. Preferred for the present invention is Aspartame. Aspartame, a methylester of the aspartic acid/phenylalaninedipeptide is a non-saccharide sweetener, which helps in maintaining tooth mineralization preventing dental caries.
The flavoring agent for the present invention are selected from a group of flavors such as citrus flavor, banana flavor, mango flavor, mint flavor, spearmint flavor, and mint flavor, preferably spearmint flavor and mango flavor used in combination or individually to impart flavor to the chewable tablet for better mouth-feel and palatability, in combination with menthol, for inducing minimal cooling effect. Coloring agents used for the present invention are selected from a group of excipients such as Tartrazine Yellow, Brilliant Blue, red iron oxide, yellow iron oxide, Titanium dioxide, preferably tartrazine yellow, brilliant blue and titanium dioxide individually or in combination thereof.

The glidants used for the present invention are selected from a group of excipients such as sodium steryl fumerate, magnesium trisilicate, powdered cellulose, talc, starch, colloidal silicon dioside, preferably colloidal silicon dioxide and talc, individually or in combination thereof.
The lubricants used for the invention are selected from magnesium Stearate and stearic acid, preferably magnesium Stearate. In the present embodiment of the invention, the process for formulating the chewable tablet which is taste masked and provides effective mouth feel, technically comprises the following steps such as:

a) First granules of active ingredient Ferrous calcium citrate is being coated with Anionic copolymer preferably with Methacrylic acid - Ethyl acrylate copolymer and suitable chosen excipients for gastro-resistant activity

b) The active drug gastro-resistant granulates are than coated with Cationic polymer preferably with Basic Butylated Methacrylate Copolymer giving a granules with taste masking and acid resistant activity.

c) The second active ingredient Folic acid being granulated with chosen suitable excipients preferably Shellac as binder to promote stability of folic acid as moisture barrier

d) Folic acid granulates and Granulates with Ferrous calcium citrate having gastro-resistant and taste masking effect blended with other suitable excipients such as combination of diluents like mannitol, sorbitol and maltodextrin for palatability and mouth feel effect, and preferably with other excipients such as disintegrant, Acidulating agent, alkalizer, sweetening agent, flavoring agents and glidant.

e) Lubricating the granule mass with Magnesium Stearate.

f) Compressing the granulate lubricated mass into suitable chewable tablets

g) Seal coating of the tablets with moisture barrier coating polymer such as Opaglos NA 7150.

h) Film coating of seal coated tablets, the film coat comprising of a sweetening agent and a flavoring agent. Other than in the operating examples, or where otherwise indicated, all numbers expressing quantities of ingredients, parameters, or reaction conditions used herein are to be understood as modified in all instances by the term "about".

In an embodiment, the invention provides a process for the preparation of Gastro-resistant granulation of chewable tablet of the active ingredient from herein referred to as "Active moiety 1", comprising coating the granules of the active ingredient, preferably Ferrous calcium Citrate with Methacrylic acid copolymer and suitable chosen excipients for gastro-resistant activity. The steps are as follows:

a) Accurately weighing and dispensing "active Moiety 1" with a diluent (Maltodextrin) and shifting it through Sieve no 30 to 80# (preferably 40#), made of Stainless Steel., from hereto referred as 'S.S'.

b) Dissolving weight colorants (Tartrazine Yellow and Brilliant Blue) in water, followed by Methacrylic acid copolymer (anionic copolymer) of Eudragit L Grade slowly into the above solution and stir for approximately 5-20 minutes.

c) The polymer powder of Methacrylic acid copolymer is thoroughly wetted and lump or foam formation is avoided, the above dispersion used as the binder solution.

d) Charging the above shifted material of "active moiety 1" and Maltodextrin into a fluid bed processor referred here to as "FBP"and mix for 5-20 minutes, with flap positions being around 10 - 50% without heater.

e) Spraying of the above binder solution of Methacrylic acid copolymer on to the mixed blend by monitoring the process parameters such as inlet temperature, product temperature, exhaust temperature, atomization air pressure, RPM flap positions, as specified below

f) Inlet Temperature is maintained about 35-70° C, and the product temperature is maintained about 25-40° C, and exhaust temperature is maintained about 25-45° C.

g) The atomization air pressure is maintained about 1.5 to 4 Bar, and peristaltic pump is maintained at about 20 - 80 RPM, and the flap position is maintained about 20 - 70%.

h) After completion of spraying, wet mass is raked and subjected to drying the wet granules in Fluidized Bed Processor. Inlet temperature is maintained about 40 to 70°C, Product temperature is maintained about 30 to 45°C, Exhaust temperature is maintained about 30 to 50°C as specified below

i) The flap position at about 20 to 70 % for about 20-60 minutes. LOD Limit is maintained about 1.5 to 3.0 %w/w.

j) Shifting the dried granules through S.S Sieve No. 16 to 30# (preferably 20 #), using vibratory shifter.

k) Passing of Granule retains through multi-mill, fitted with S. S. 1.0 mm to 2.5mm (preferably 1.5mm) Screen, with knives forward at low to moderate speed, followed by milled granules passed through S.S Sieve No 16 to 30# (preferably 20 #), finally obtaining the Gastro-resistant granulates.

The invention further provides a process for the preparation of taste masking granules of the chewable tablet of the "active moiety 1" by using the gastro-resistant granulates of the "active moiety 1", comprising coating the gastro-resistant granules of "active moiety 1" with Methacrylate copolymer and suitable chosen excipients for taste-masking activity. The steps are as follows:

a) Dissolving accurately weighed Methacrylate copolymer (cationic copolymer) of Eudragit E Grade in a suitable solution. The binder solution preferably being suitable non-aqueous solvent, more preferably Ethanol.

b) Charging the Gastro-resistant granules of "active moiety 1" into the 'FBP' followed by spraying of the Ethanolic solution of Methacrylate copolymer (cationic copolymer) on to the Gastro-resistant granules of "active moiety 1" by monitoring the process parameters such as inlet temperature, product temperature, exhaust temperature, atomization air pressure, RPM, flap positions, as specified below

c) Inlet Temperature is maintained about 25-40° C, and the product temperature is maintained about 20-30° C, and exhaust temperature is maintained about 20-35° C.

d) The atomization air pressure is maintained about 1.5 to 4 Bar, and peristaltic pump is maintained at about 20 - 80 RPM, and the flap position is maintained about 20 - 70%.

e) Raking the wet mass and drying in 'FBP'. By monitoring process parameters as specified below

f) Inlet temperature is maintained about 30-40°C, Product temperature is maintained about 20-30°C, Exhaust temperature is maintained about 20-35°C

g) The flap position at about 20 to 70 % for about 20-60 minutes. LOD Limit is maintained about 1.5 to 3.0 %w/w.

h) Shifting the dried granules through S.S Sieve No. 16 to 30# (preferably 20 #), using vibratory shifter.

i) Passing of Granule retains through multi-mill, fitted with S. S. 1.0 mm to 2.5mm (preferably 1.5mm)Screen, with knives forward at low to moderate speed, followed by milled granules passed through S.S Sieve No 16 to 30# (preferably 20 #), finally obtaining the Taste -masking layer above gastro-resistant granulates giving taste-masked granulates.

The invention of present embodiment provides a process for granulation for the said chewable tablet with another active ingredient, preferably folic acid, from here in referred to as "Active Moiety 2", comprising suitable excipients and a binder solution made to provide moisture barrier, preferably made with shellac, the steps are as follows:

a) Accurately weighing and dispensing "active moiety 2" with diluent and a dry binder such as Mannitol and Povidone K-30, followed by shifting through S. S. Sieve No. 30 to 60# (preferably 40#).

b) Dispensing moisture barrier excipient (Shellac) and adding to a suitable solvent. The suitable solvent preferably being Isopropyl Alcohol. Followed by soaking for about 6 to 24 hours, and after used as a binder solution.

c) Charging the above shifted material of "active moiety 2" into rapid mixer granulator referred hereto as "RMG", followed by granulation by monitoring process parameters such as Mixing time, Binder addition, Speed rate

d) Initial Mixing time for about 5 to 20 minutes at slow speed. Followed by addition of 50-80 % of binder to dry mix present in RMG, under slow speed for 2 to 5 minutes.

e) Raking the wet mass in RMG, if necessary. Adding remaining quantity of binder, continue mixing for 4 - 8 minutes with impeller at slow and chopper slow until desired wet mass obtained.

f) Discharging the wet mass of into FBP bowl by opening the discharge port and operating the impeller at slow rate.

g) Drying the granules comprising 'Cycle 1' and 'Cycle 2'

h) Cycle - 1: Air drying the granules in FBP bowl, without application of heat for about 10 - 30 Minutes followed by Cycle - 2.

i) Cycle - 2: Raking the wet mass and continuing drying in FBP by monitoring the process parameters such as inlet temperature, drying time and LOD, specified as below

j) Inlet temperature maintained of about 40 - 70°C for about 20-60 minutes, with in the LOD limit of about 1.0-3.0%

I) Shifting the dried granules through S.S Sieve No. 20 to 60#(preferably 40#), using vibratory shifter.

k) Passing of Granule retains through multi-mill, fitted with S. S. 0.5 to 2.0mm (preferably 1.0 mm) Screen, with knives forward at low to moderate speed, followed by milled granules passed through S.S Sieve No 20 to 60#(preferably 40#), The obtained granules of Active Moiety 2 are subjected to pre-lubrication with suitable excipients.

The invention further provides a process of combined pre-lubrication and lubrication of the Taste-masked gastro-resistant granules of active ingredients preferably being Ferrous Calcium Citrate, and Folic acid Granules comprising moisture barrier, comprising suitable excipients such as Diluents, disintegrant, Sweeteners, Flavors, acidifiers, alkalizers, a glidant and a lubricant. The processes in the steps are as follows:

a) Accurately weighing and dispensing diluents (Mannitol, sorbitol), disintegrant (Sodium starch glycollate), sweetener (aspartame) and Flavors (Mango and Spearmint flavor), followed by shifting through S.S Sieve. No. 30 to 100# (preferably 40 #).

b) Accurately weighing and dispensing Acidifier (Citric acid), Alkalizer (Sodium citrate), and a flavor/cooling agent (Menthol), followed by shifting using S.S. Sieve. No. 40 to 120# (preferably80#).

c) Transfer the above sifted materials into the blender containing dried and milled granules of Gastro-resistant, Taste-masked granules of 'Active moiety 1' and Moisture barrier granules of Active moiety 2.

d) Blending for 10 to 30 minutes (preferably 20 minutes) at slow rate. The pre-lubricated blend obtained for lubrication process.

e) Accurately weighing and dispensing lubricant (Magnesium Stearate), followed by shifting through S.S. Sieve No 40 to 100# (preferably 60 #).

f) Transferring into blender containing Pre-lubricated blend and blending for 2-5 minutes

The process of invention in the present embodiment further provides the appropriate limits for the monitoring of blend parameters such as bulk density, tapped density, Carr's compressibility Index, hausner's ratio and Sieve Analysis, the appropriate limits are as follows:

a) Bulk density should be about 0.40 to 0.60 g/cc, tapped density should be about 0.50 to 0.80 g/cc.

b) Carr's compressibility index should be about 11-20 %, hausner's ratio should be about 1.12 -1.25.

c) On sieve analysis, maximum % retained obtained by retains of granules on S.S. Sieve no 30# NMT 15.0%, and for of S. S. Sieve no 100# NLT 40.0%.

In the present embodiment of the invention there is selected a specific shape and size of the upper and lower punches for compression of taste-masked chewable tablets with good palatability and mouth-feel and for commercial and attractive purposes. In the present invention, the Upper Punch dimensions'! 0x8mm to 20*18mm, having preferably 13.21 x 10.88 mm, preferably Mango shaped, punches plain on surface. And Lower Punch dimension 10x8mm to 20^18mm, having preferably 13.21 x 10.88 mm, preferably Mango shaped, punches plain on surface, with the speed of compression maintained about 15-30 RPM.

The invention for the present embodiment of chewable tablet further provides appropriate limits for the uncoated chewable dosage form, which are as follows:

a) The appearance may be as light green to green color tablet, almost as a mango shape, or any other shape with commercial advantage, and as biconvex tablet on both sides

b) The uniformity of the weight may be as per pharmacopoeial limits, not exceeding ± 5%, as the average weight of tablets may be with deviation about ±2 %,

c) The thickness may be about 6.40-6.90mm, and the length is maintained about 12.90 -13.50mm, whereas the width may be about 10.50-11.10mm

d) The hardness may be about 100-250N

The invention of the present embodiment further provides a process of barrier coating of the said chewable tablet for purpose of moisture barrier protection and preventing oxidation, comprising coating with a suitable moisture barrier coat, by using conventional method of coating.

In the present invention, the moisture barrier coat is selected from a suitable list of excipients, preferably being shellac, preferably in esterified form, dispersed or dissolved in a suitable solvent, preferably Isopropyl Alcohol. In the present invention, the moisture barrier coat, preferably shellac is dissolved or dispersed in Isopropyl Alcohol, followed by continuous stirring during the process of coating, on maintaining the process parameters such as:

a) Inlet temperature is about 30-45°C, outlet temperature is about 30-40°C

b) Pan RPM is about 2-6 RPM, with spray rate of about 80-120ml/min.

c) Automization pressure is about 4-6Kg/cm2, and the distance between tablet bed and spray gun is maintained about 15-25 cm.

d) The final percentage weight build-up on coating may be maintained about 0.2 -2.0%.

The invention for the present embodiment of chewable tablet further provides appropriate limits for the seal-coated chewable dosage form, which are as follows:

a) The appearance may be as light green to green color tablet, almost as a mango shape, or any other shape with commercial advantage, and as biconvex tablet on both sides

b) The uniformity of the weight may be as per pharmacopoeial limits, not exceeding ± 5%, as the average weight of tablets may be with deviation about ±2%,

c) The thickness may be about 6.40-7.00mm, and the length is maintained about 12.90 -13.50 mm, whereas the width may be about 10.50-11.10mm

d) The hardness may be about NMT 300N

e) The percentage weight buildup of seal coating may be about 0.2-2.0%

In the present embodiment, it is an objective of the invention to provide a process for the film coating of chewable tablets comprising two active ingredients, further the coating comprising a sweetening agent and a flavoring agent along with other suitable excipients for effective taste-masking, good palatability and enhanced mouth feel properties. In one embodiment, the invention relates to the process for film coating of the said chewable tablets comprising excipients such as coating polymer, plasticizer, sweetening agent, flavoring agent, colorant, glidant and opacifier, in alone or in combinations of the same type, dispersed or dissolved in a suitable solvent or a mixture of solvents The coating polymer for the present invention is selected from a group of cellulose based derivatives such as Hydroxypropyl Cellulose (HPC), Hydroxyethyl Cellulose (HEC), Hydroxy Propyl Methyl Cellulose (HPMC), preferably chosen is HPMC, for its effective film forming properties and solubility in water The plasticizer for the present invention is selected from a group of excipients such as triethyl citrate, acetyl triethyl citrate, polyethylene glycol and propylene glycol. Preferably chosen is polyethylene glycol and most preferably chosen is PEG 6000, due to its high molecular weight and effective plasticization of the film comprising other excipients.

Sweeteners used for the present invention are Non-saccharides such as Sucralose, Aspertame, Saccharin and Neotame. They are non-cariogenic and maintain tooth mineralization
Preferred for the present invention is Aspartame. Aspartame, a methylester of the aspartic acid/phenylalanine dipeptide is a non-saccharide sweetener, which helps in effective taste-masking and to induce mouth-feel property. The flavoring agent for the present invention are selected from a group of flavors such as citrus flavor, banana flavor, mango flavor, mint flavor, spearmint flavor, and mint flavor, preferably spearmint flavor to impart flavor to the chewable tablet for better mouth-feel and palatability, Coloring agents used for the present invention are selected from a group of excipients such as Tartrazine Yellow, Brilliant Blue, red iron oxide, yellow iron oxide, Titanium dioxide, preferably tartrazine yellow, brilliant blue and titanium dioxide (used as an opacifier) individually or in combination thereof, In the present embodiment of the invention, the process for taste-masking film coating for said chewable tablet involves the use of a suitable hydro-alcoholic preparation, preferably the ratio of Isopropyl alcohol: Water of 1:1, to 1:4, most preferably in the ratio of 1:2.5

In the present embodiment of the invention, the process for taste-masking film coating is performed based on monitoring of process parameters such as:

a) Inlet temperature is about 35-50°C, outlet temperature is about 35-40°C

b) Pan RPM is about 2-6 RPM, with spray rate of about 80-160ml/min.

c) Automization pressure is about 4-6Kg/cm2, and the distance between tablet bed and spray gun is maintained about 15-20 cm.

d) The final percentage weight build-up on coating may be maintained about 1-5%. In the present invention, there is provided the appropriate limits of the dosage unit physical parameters, which may be maintained within the final product obtained as the effective taste-masking gastro-resistant chewable tablet with good palatability and mouth feel properties. In the present invention, the tablet parameters for the final seal/film coated chewable tablets with appropriate limits, for an optimized product are as follows:

f) The appearance may be as green color tablet, almost as a mango shape, or any other shape with commercial advantage, and as biconvex film coated tablet on both sides

g) The uniformity of the weight may be as per pharmacopoeial limits, not exceeding ± 5%, as the average weight of tablets may be with deviation about ±2 %.

h) The thickness may be about 6.50-7.10mm, and the length is maintained about 13.00 - 13.60mm, whereas the width may be about 10.60-11.20mm. i) The hardness may be about not more than 300N

The present invention also provides a process for in-vivo evaluation of improved organoleptic properties such as appearance, taste, smell and mouth feel. The evaluation is done by selected internal panel of 5 subjects with varying age groups, done for formulations, comprising varying combinations and amounts of various ingredients In the present invention, the internal panel of 5 subjects with different age groups are selected by choosing 5 men. The men selected were clinically evaluated for xerostomia before the evaluation. The subjects being 5men from age groups of 25-30 In the present aspect of the invention, the organoleptic properties such as appearance, taste, smell and mouth-feel are recorded for different formulations, as such given in Example 2 Below. All organoleptic properties are recorded as descriptions as described by the subjects, and the time of response from the point of administration, while masticating the said chewable dosage tablet The method described below are not intended to be limiting, but rather as exemplary of the novel excipient base and other tablet formulations of the present invention.

BRIEF PROCESS

In one particular aspect of the invention, the Example - 1 below relates to the formulation and the process of the said chewable tablet dosage form is described in the Example below detailing the various steps, involved in the process for manufacturing of the said dosage unit

EXAMPLE -1

FORMULATION

STAGE I: GRANULATION:

PART I: (API GASTRO RESISTANT GRANULATION)

STEP 1. DISPENSING & SIFTING:

Accurately weigh and sieve Ferrous calcium citrate complex, Maltodextrin using 40 # S.S. Sieve and collect in the S.S. bin.

STEP 2. BINDER PREPARATION:

Dissolve accurately weighed Tatrazine yellow, Brilliant blue in Purified water. Add the Methacrylic acid copolymer (anionic copolymer) slowly into the above solution and stir for approximately 5 minutes. Make sure that the powder is thoroughly wetted and lump or foam formation is avoided, the above dispersion used as the binder.

STEP 3. DRY MIXING & GRANULATION:

Charge the above sifted material in the Fluidized Bed Processor. Mix total for 10 minutes in the Fluidized Bed Processor with the Flap position at 10 to 50% (Target -20%) without heater.

STEP 4. DRYING THE GRANULES:

After completion of spraying, rake the wet mass and continue drying the wet granules in Fluidized Bed Processor. Inlet temperature of 40 to 70°C, Product temperature- 30 to 45°C, Exhaust temperature- 30 to 50°C & flap position at 20 to 70 % for 30 minutes. LOD Limit: 1.5 to 3.0 %w/w. LOD parameter: 105°C

STEP 5. DRY SIFTING & MILLING:

Pass the dried granules through 20 # Vibro sifter & collect the retains, Pass the retains through Multimill fitted with 1.5mm screen with knives forward at slow speed & Collect in a poly bag. Pass the milled granules through 20# sieve, Ensure that all the granules are passed through 20# sieve. Charge the above sifted material in the Fluidized Bed Processor.

PART II: (API TASTE MASKING GRANULATION):

STEP 1. BINDER PREPARATION:

Dissolve accurately weighed Methacrylate copolymer (cationic copolymer) in Ethanol 95% used as the binder solution.

STEP 2. GRANULATION Charge the above sifted material in the Fluidized Bed Processor.

STEP 4. DRYING THE GRANULES:
After completion of spraying, rake the wet mass and continue drying the wet granules in Fluidized Bed Processor. Dry the wet mass without application of heat for 1 hour, followed by Inlet temperature of 30 to 45°C, Product temperature- 20 - 30°C, Exhaust temperature- 20 to 35°C & flap position at 20 to 70 % for 30 minutes. LOD Limit: 1.5 to 3.0 %w/w. LOD parameter: 105°C

STEP 5. DRY SIFTING & MILLING:

Pass the dried granules through 20 # Vibro sifter & collect the retains, Pass the retains through Multimill fitted with 1.5mm screen with knives forward at slow speed & Collect in a poly bag. Pass the milled granules through 20# sieve, Ensure that all the granules are passed through 20# sieve. Charge the above sifted material in the blender.

PART III: FOLIC ACID GRANULATION:

STEP 1. DISPENSING & SIFTING:

Accurately weigh and sieve Folic acid, Mannitol, Povidone K30 using 40 # S.S. Sieve and collect in the S.S. bin.

STEP 2. BINDER PREPARATION:

Dispense and take Isopropyl alcohol in a stainless steel vessel and add Shellac under stirring. Allow the solution to soak for 8 to 12 hours. This solution is to be used as binder.

STEP 3. DRY MIXING & GRANULATION:

Charge the above sifted material in the Rapid Mixer Granulator. Mix total for 10 minutes at slow speed. Add 70 % of binder to dry mix present in Rapid Mixer Granulator under slow speed for 2 minutes. Rake the mass in Rapid Mixer Granulator, if necessary. Add remaining quantity of binder, continue mixing for 4 - 5 minutes with impeller at slow and chopper slow until desired wet mass obtained. Discharge the wet mass into Fluidized Bed Processor bowl by opening the discharge port and operating the impeller at slow.

STEP 4. DRYING THE GRANULES:

CYCLE I: Distribute the material uniformly in the Fluidized Bed Processor bowl using S.S. paddle. Start the Fluidized Bed Processor and air dry the wet mass without application of heat for 10 minutes.

CYCLE II: Rake the wet mass and continue drying the wet granules in Fluidized Bed Processor at an inlet temperature of 40 - 70°C for 30 minutes. LOD Limit: Between 1.0 - 2.5 % w/w. LOD parameter: 105°C

STEP 5. DRY SIFTING & MILLING:

Sift the dried granules through 40# SS sieve using vibratory sifter. Collect the retention in a poly bag. Pass the retention granules through multimill fitted with 1.0 mm screen Knives forward at slow. Collect the milled granules in a double lined polythene bag. Charge the above sifted material in the blender.

STAGE-II PRE-LUBRICATION:
Accurately weigh and sieve Mannitol SD 200, Sorbitol crystalline, Colloidal silicon dioxide, Sodium starch glycolate, Aspartame, Mango green flavor, Spearmint flavor using 40 # S.S. Sieve and collect in the S.S. bin. Accurately weigh and sieve Citric acid anhydrous, Sodium citrate, Menthol using 80 # S.S. Sieve and collect in the S.S. bin. Transfer the above sifted materials into the blender containing dried and milled granules of Ferrous calcium citrate & Folic acid. Blend for 20 minutes at slow.

STAGE- III LUBRICATION:

Accurately weigh and sieve Magnesium stearate using 60 # S.S. Sieve and collect in the S.S. bin. Transfer sifted Magnesium stearate into the blender & Blend for 3 minutes.
Evaluation of the Lubricated blend:

STAGE IV: COMPRESSION:

Upper Punch: 13.21 x 10.88 mm Mango shaped, punches plain on surface. Lower Punch: 13.21 x 10,88 mm Mango shaped, punches plain on surface. Dies: 13.21 x 10.88 mm
PARAMETERS FOR UNCOATED TABLETS

STAGE V:COATING:

PART I: BARRIER COATING:

Place Isopropyl alcohol in a stainless steel and slowly incorporate Opaglos (Esterified shellac) in to it. Maintain continuous stirring for 30 minutes. Maintain continuous stirring during the implementation of the coating.

PARAMETERS FOR SEAL COATED TABLETS

PART II FILM COATING:

Place purified water in a stainless steel vessel and slowly incorporate Opadry green (Hypromellose, Lactose monohydrate, Maltodextrin, PEG -6000, Talc, Titanium dioxide, Aspartame, Spearmint flavor, Tartrazine Yellow Supra & Brilliant Blue) under continuous stirring. Continue stirring till a smooth dispersion is obtained. Incorporate isopropyl alcohol to the coating dispersion, Continue stirring for 15 minutes. Filter the coating suspension through 100 # mesh sieve. The compressed tablets loaded in a coating pan, coating solution sprayed over the tablet to required weight buildup.

PARAMETERS FOR SEAL COATED & FILM COATED TABLETS
STAGE VI: PACKING:

Clear PVDC/Aluminium Blister (Triplex 90gsm). In one particular aspect of the invention, the Example - 2 below relates to the formulation and the process of the said chewable tablet dosage form being described for oragnoleptic properties such as by the subjects and their responses

EXAMPLE - 2

CHEWABLE FORMULATIONS OF VARYING COMPOSITION AND COMBINATIONS

SUBJECT IN-VIVO EVALUATION AND DESCRIPTION OF PRODUCT - Formulation-1

SUBJECT IN-VIVO EVALUATION AND DESCRIPTION OF PRODUCT - Formulation - 2

SUBJECT IN-VIVO EVALUATION AND DESCRIPTION OF PRODUCT - Formulation - 3

ADVANTAGE OF THE INVENTION:

Chewable tablets are a convenient alternative to conventional tablets. They have the great advantage of not requiring water, which means that they can be taken at any time and in any place. When used in combination with other dosage forms, like effervescent tablets, chewable tablets offer additional variety for patients, improving the experience and ensuring better compliance. In the present invention, the formulation provided for the manufacture of the chewable tablets helps in obtaining an effective chewable dosage unit, which tend to show good payability, pleasant tasting and enhanced acceptable mouth-feel qualities, providing over-all effective taste-masking Chewable tablets of the said invention obtained by the reasonable formulation of multi-layer particle (granule) coating technology is specifically designed to release the active ingredient (Hematinic) into duodenum, allowing effective iron absorption. Also providing taste-masking of the bitter nutritional supplement such as folic acid, in-turn providing moisture-barrier for folic acid as well as the whole dosage unit, in combination with taste-masking film coating. The chewable tablets of the said invention obtained by the reasonable formulation is designed to eliminate dryness of mouth and dental caries, and facilitating enhanced iron absorption on targeted release into the duodenum. The chewable tablets of the said invention obtained by the reasonable formulation is designed with the combined advantages of Gastro-resistant activity, taste masking effect, good palatability and mouth-feel, targeted duodenal release.

The chewable tablet designed by the process in the present invention aims at proving a dosage unit designed to provide better patient compliance of especially pregnant woman as Anti nauseating therapeutic product.

Benefits

• Create a more 'user-friendly' experience . Eliminate need to take water with tabletsFoi" BAF NA PHARMACEUTICALS LTD.

• Increase compliance

• Overcome swallowing difficulties
• Reduce risk of esophagitis

• Dose precisions

• Higher Palatability

• Better availability

• Easy of administration while traveling

• Portability

CLAIMS:

1. A Formulation for obtaining chewable tablet, providing gastro-resistant, good palatability, pleasant and enhanced mouth-feel qualities, effective taste-masking and a targeted release of active ingredient in the duodenum, the process comprising:

a) Enteric Coating with pH-dependent Anionic and cationic copolymers said to possess gastro-resistant and taste-masking properties of metallic tasting hematinic.

b) Incorporation of mouth-feel enhancing diluents, acidifier, alkalizer, sweetening agent and a flavoring agents by pre-lubrication process

c) Seal coating with a moisture - barrier excipient to avoid oxidation and moisture-attack

d) Film coating comprising sweetener and a flavor, in a hydro-alcoholic solvent

2. The formulation according to Claim 1, where the active ingredients is a hematinic, preferably Ferrous calcium citrate and a nutritional supplement, preferably folic acid.

3. The formulation according to Claim 1, where the anionic copolymer is Methacrylicacid Copolymer, preferably a Methacrylic acid - Ethyl Acrylate Copolymer, (Eudragit L100-55).

4. The formulation according to Claim 1, where the cationic copolymer is Methacrylate Copolymer, preferably Basic Butylated Methacrylic Copolymer (Eudragit E 100).

5. The formulation according to claim 1, where the solvent for Methacrylic acid copolymer is water with colorants, preferably Tartrazine yellow and brilliant blue, and with a diluents preferably maltodextrin.

6. The formulation according to claim 1, where the solvent for Methacrylate copolymer is Ethanol.

7. The formulation according to claim 1, where the cationic and anionic co-polymer coating is done by binder solution through wet granulation method

8. The process according to claim 1, where the anionic polymer (Methacrylic acid Copolymer) coating is done followed by cationic co-polymer (Methacrylate copolymer)

9. The process involving moisture-barrier of folic acid, with shellac, as binder solution, by the process of wet granulation, through Rapid Mixer granulator

10. The formulation according to claim 1, where the mouth-feel enhancing diluents are preferably sorbitol, mannitol and maltodextrin.

11. The formulation according to claim 1, where a sweetening agent, preferably aspartame, is used in combination with flavors, preferably Mango flavor, spearmint flavor and menthol.

12. The process wherein the tablet assumes the shape of the mango green, with biconvex and plain on both sides.

13. The process according to claim 1, where the seal coat, preferred is esterified shellac, preferably with percentage weight buildup of 0.2-1.0%

14. The process according to claim 1, where the film coat comprises the same sweetener, flavor and colorants as used in granulation and pre-lubrication.

15. The formulation according to claim 1, where the percentage weight build-up of coating is preferably 1.3%