chewable tablets

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Formulation ,Manufacture & Evaluation of Chewable tablets :

Formulation ,Manufacture & Evaluation of Chewable tablets P.Sindhuka m.pharm Pharmaceutical technology

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Commercially available Chewable tablets The tablets are placed in the mouth, chewed and swallowed. Eg : Talcid ,( Aspirin Direct) CELIN, Vit - C ENTASID, Al(OH)2

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Excipents of Chewable tablet : In addition to active ingredients, tablet contains a number of inert materials known as additives or excipients . Varrious excipients of Chewable tablet are: Diluent Disintegrants Binder and adhesive Lubricants and glidants Colouring agents Flavoring agents Sweetening agents

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Diluents Mannitol xylitol Sorbitol Sucrose Starch Diluents are fillers used to increase the bulk volume of a tablet. By combining a diluent with the active pharmaceutical ingredients, the final product is given adequate weight and size to assist in production and handling .

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Mannitol Mannitol in various polymorphic forms is the main excipient of chewable tablets. Gives pleasant mouth feel due to negative heat of solution. Mannitol has about 72% as sweet as sucrose. Mannitol is nonhygroscopic and shows a low reactivity with drug substances. Chewable vitamins and antacids are prepared .

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Mannitol formulations, because of their poor flow properties, usually require higher lubricant levels and higher glidant levels for satisfactory compression than other diluents. A granular form of mannitol is available as a direct-compression excipient . Mannitol has been shown to be chemically compatible with moisture-sensitive compounds. It picks up less than 1% moisture at relative humidities as high as 90%.

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Mannitol is substituted by xylitol , Sorbital , lactose, dextrose,hydrolyzed starches. Mannitol and sorbitol are noncariogenic sugars and are of low nutritional and caloric content. Xylitol It is used in sugar free chewable tablets preparation. Xylitol is sweeter than mannitol & has desirable – ve heat of solution that provides cooling effect.

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Sorbitol Sorbitol is an optical isomer of mannitol but differs from it in that sorbitol is hygroscopic at humidities above 65%. Sorbitol is more watersoluble than mannitol . Hygroscopic and will clump in the feed frame and stick to the surfaces of the die table when tableted at humidities > 50%

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Sucrose Di-Pac: cocrystallization of 97% sucrose and 3% modified dextrin. Good flow properties and needs a glidant only when atmospheric moisture levels are high (>50%RH). Nutab : 95.8% sucrose, 4% invert sugar (equimolecular mixture of levulose and dextrose) and 0.1 to 0.2% each of cornstarch and magnesium strarate . Sugartab :( 90 to 93% sucrose plus 7 to 10% invert sugar)

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Above 3 types have good palatability and mouth-feel and can minimize the need for artificial sweeteners due to their high sucrose level. NuTab available in two forms coarse, medium. The medium grade of NuTab , in moisture uptake studies, initially took on moisture more rapidly than the coarse but both reached the same equilibrium uptake of 3.3 to 3.5% after 2 weeks at 80% relative humidity. Confectioner's sugar used as a diluent but does require granulation to impart bonding if present at significant levels.

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STARCH Emdex and Celutab are hydrolyzed starches. 90-92% dextrose, 3-5% maltose and the remainder higher glucose polysaccharides. Excellent compressibility and good flow Contain 8-10% moisture and may increase hardness after compression. Dextrose commercially available as Cerelose , can be used as filler, carrier, and extender where a sweet material is desired.

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It is available as a hydrate ( Cerelose 2001) and in an anhydrous form ( Cerelose 2401) where low moisture is needed. It can be used to replace spray-dried lactose in direct-compaction formulas. It requireshigher lubricant levels than spray-dried lactose and it has lesser tendency to turn brown. Inositol is used as a replacement diluent for chewable tablets employing mannitol , lactose, and a sucrose-lactose mixture .

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Binders and Adhesives: Poly vinyl pyrrolidone (PVP) These materials are added either dry or in wet- form to form granules or to form cohesive compacts for directly compressed tablet. Poly vinyl pyrrolidone (PVP) is an alcohol-soluble material which is used in concentrations between 3 and 15%. Granulations using a PVP-alcohol system granulate well, dry rapidly, and compress extremely well. PVP finds particular application in multivitamin chewable formulations where moisture sensitivity can be a problem.

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Lubricants: Reduce friction between the granulation and die wall during compression and ejection. Eg : Stearates (Magnesium,calcium,sodium) in the range of (0.25 – 2 %),Talc (1-5%). Glidants : to promote flow of granules or powder material by reducing the friction between the particles. Eg:syloid (synthetic silica). Antiadherents: Prevent sticking to the punch and, to a lesser extent,the die wall.

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Coloring agents Masking of off color drugs. Product Identification. Production of more elegant product. Two forms of colors are used in tablet preparation – FD &C and D & C dyes & lakes. Dyes are water-soluble materials, lakes are formed by the absorption of a water-soluble dye on a hydrous oxide (usually aluminum hydroxide) which results in an insoluble form of the dye. lakes added in dry form .

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Colors near the mid-range of the visible spectrum (yellow, green) will show less mottling than those at either extreme (blue, red) Dyes are usually dissolved in the granulating system for incorporation during the granulating process. Example: FD & C yellow 6-sunset yellow FD & C yellow 5- Tartrazine FD & C green 3- Fast Green FD & C blue 1- Brilliant Blue

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Flavors and Sweeteners Flavor's are incorporated as solids in the form of spray-dried beadlets and oils, usually at the lubrication step, because of the sensitivity of these materials to moisture and their tendency to volatilize when heated(during granulation drying). eg:sweet - venilla,sour - citrus,bitter -mint. Sweeteners are added primarily to chewable tablets when the commonly used carriers do not sufficiently mask the taste of the components. Saccharin is about 450 times sweeter than Sucrose,major disadvantage is its bitter aftertaste.cyclamates (30-50), glycyrrhizin(50), aspertame (200).

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FORMULATION TECHNIQUES Coating by Wet granulation: This process agglomerates drug particles through a combination of adhesion and cohesion using a wetting agent and binder then finally get the free flowing,compressible granules. it may be useful in the application of coatings to drug particles in order to mask their taste. the use of ethylcellulose (water-insoluble polymer) to coat ascorbic acid through wet granulation to improve its stability and assist in taste masking.

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flUidized bed or air suspension technique: drug particles to be coated are fluidized by means of suspension in a controlled, high-velocity. warm air stream directedthrough a perforated plate into a coating chamber. The drug particles undergo cyclic flow past an atomizing nozzle delivering coating agent in solution or suspension. The sprayer may be mounted either to spray upward from the bottom (Wurster style) or downward from the top. Fluidization of the drug particles provides increased Surface exposure for more efficient and uniform coating and drying. This permits the coating of heat-labile drugs without concern for degradation.

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Microencapsulation: Formation of three immiscible phases: a liquid-manufacturing vehicle phase, a core material drug phase. and a coating material phase. Depositing the liquid polymer coating by sorption around the core material under controlled physical mixing of the three phases Rigidizing the coating. usually by thermal crosslinking or desolvation techniques, to form a rigid microcapsule. The resultant coated granules not only mask the taste of a drug but also minimize any physical and chemical incompatibility between ingredients

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Solid dispersions: Bad-tasting drugs can be prevented from stimulating the taste buds by adsorption onto substrates capable of keeping the drugs adsorbed while in the mouth but releasing them eventually in the stomach or GIT. Eg:adsorption of dextromethorphanHBr on to magnesium trisilicate substrate. bentonite,Veegum, and silica gel are used as a substrates.

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Adsorbate Formation Techniques Solvent Method: dissolving the drug in a solvent mixing the solution with the substrate and evaporating the solvent-leaving the drug molecules adsorbed upon the substrate. choice of solvent,substrate,proportions,mixing conditions, rate of evaporation, and temperature, must be optimized. Melting Method: Here the drug and a carrier are melted together by heating. The melted mixture is then cooled and rapidly solidified in an ice bath with vigorous stirring .

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Heatlabile drugs, volatile drugs, and drugs that decompose on melting are obviously unsuitable for this method. Ion Exchange: reversible interchange of ions between a solid and a liquid phase . The solid is the ion exchange material while the ion could be a drug . Strong acid cation exchange resins: principal sulfonated styrene-divinylbenzene copolymer products . function throughout the entire pH. used for masking the taste and odor of cationic (amine-containing) drugs.

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weak acid cation exchange resins : these prepared by crosslinking an unsaturated carboxylic acid such as methacrylic acid with a crosslinking agent such as divinylbenze. function at pH values above 6. Strong base anion exchange resins: These are quaternized amines. function throughout the entire pH range. Weak base anion exchange resins : Dimethylamine is usually used. function well below pH 7. particle size, shape, density, porosity, chemical and physical stability, and ionic capacity.

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Spray Congealing and Spray Coating: the process of spray congealing involves cooling (or congealing) of melted substances in the form of fine particles during their travel from a spray nozzle to spraying chamber at a temperature below their melting point. For small-dose entities, such as the vitamins, spray congealing is ideally suit e d. Polyethylene glycols(4000-20,000) are suitable.

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spray-coating process involves the spraying of a suspension of the drug particles in a solution of the coating material through an atomizer into a high-velocity stream of warm air. The coarse droplets delivered by the atomizer consist of drug particles enveloped by coating solution. As the solvent evaporates, the coating material encapsulates the drug particle. this process suitable for heat-labile drugs.

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Formation of Different Salts or Derivatives: a less bitter tasting salt form or a tasteless derivative can be obtained.this would represent the best approach to taste masking. Use of Amino Acids and Protein Hydrolysates: By combining amino acids, their salts, or a mixture of the two it is possible to reduce the bitter taste of penicillin.

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Inclusion Complexes: The complex is capable of masking the bitter taste of the drug by both decreasing the amount of drug particles exposed to the taste buds and by decreasing the drug solubility on ingestion. Inclusion-type complexes can also increase the stability of the guest molecule by shielding it from moisture, oxygen, and light.

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Molecular Complexes : Molecular complex formation involves a drug and a complexing organic molecule. Eg: caffeine and gentisic acid. MANUFACTURING: Antacids Cough /Cold Analgesics Vitamins/Minerals/Food Supplements

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Vitamin C Chewable Tablet: Ingredients (mg )tablet Sodium ascorbate 170.5 mg Ascorbic acid 103.5 mg Compressible sucrose 336mg Flavoring agent 5mg Magnesium stearate 3 mg FD&C Yellow #6 Lake ( iet-rn ilied ) 2 mg

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Evaluation tests: In-Process Organoleptic Evaluation: Taste, flavour compared with standard drug. Chemical Evaluation : Assay for Drug Content : Determine the active drug content in 20 randomly selected tablets . Dosage Uniformity: If drug content is low in tablet then individuval dosageform drug content can be estimated. In Vitro and In Vivo Evaluation: Tablet power is added to 40ml water then kept for 1min to this add 10ml 0.5N HCl kept for 10min & check PH if below 3.5 rejected .

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INVIVO we use device known as a Heidelberg capsule & it has capable of sending a radiotelemetric pH recording signal from within the stomach. Physical Evaluation Tablet physical appearance. Hardness Friability –Ability to resist chipping and abrasion on handling .Done by using Roche friabilator. 4% acceptance due to lower hardness. Disintegration. Dissolution. Stability testing - overages

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References PHARMACEUTICAL DOSAGE FORMS TABLETS VOL 1, 2 ND EDTION, EDITED BY Herbert A. Lieberman,Leon Lachman ,Joseph B. Schwartz. ANSEL’S PHARMACEUTICAL DOSAGE FORMS AND DRUG DELIVERY SYSTEMS, 8 TH EDTION Leyd v.Allen,jr.Nicholas,Howard.c.Ansel .

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