ASSISTANT PROFESSOR B.PHARM FIFTH SEMESTER FORMULATIVE & INDUSTRIAL PHARMACYCONTENTS e Introduction ¢ Classification of Tablets e Excipients used in Formulating Tablets * Tablet Granulation & Its Importance e Methods of Granulation * Tablet Compression Machines « Equipment tooling e Compression Processing Problems during Tablet Manufacturing ProcessINTRODUCTION Pharmaceutical Tablets :- are solid dosage forms containing one or more drugs with or without the addition of excipients, eAddictives or excipients are mainly incorporated to enhance physical appearance, stability, disintegration, or breakup of tablet after administration. eAccording to Indian Pharmacopoeia, pharmaceutical tablets are flat or bi-convex discs manufactured by compressing a drug or a mixture of rugs with or without suitable excipients.Ideal Characteristics of Tablets The objective of the design and manufacture of the compressed tablet is to deliver orally the correct amount of drug in the proper form, at or over the proper time and in the desired location, and to have its chemical integrity protected. Should be an elegant product, free from defects. eShould have strength to withstand the harshness of mechanical shock that can be encountered in its production, packaging, shipping etc. Must be able to release the medicinal agent in the body in a predictable and reproducible manner. «Must be uniform in weight and drug content. Size and shape of tablets influence the passing of product through GIT. «Tablets should be physically and chemically stable so that no alternation of Active ingredient with time.Advantages of Tablets vCheapest oral dosage form, easy to handle, convenient to administer and offers greatest dose precision. vHave the best combined properties of chemical, mechanical, and microbiological stability of all the oral forms. vGreatest ease of swallowing, and less shelf storage space, vy Suitable for large scale production vUnpleasant and bitter tasting drugs when formulating, the taste can be masked with excipients suitable. vProvide protection of medicaments fromDisadvantages of Tablets v Some of drugs, due to their highly amorphous nature and low density, are difficult to compress. vChances of loss of ingredients of tablets during manufacturing because of involvement of several unit of operation. vDrugs with poor wetting properties and slow dissolution rate are difficult to be dispensed in the form of tablets. vDrugs with objectionable odour and bitter tasting substance need special treatment for compression. This can increase the cost of production. v Bioavailability problems may arise due to slow disintegration and slow dissolution “Some drugs can cause irritant effect on the GIT.CLASSIPICALIUIN UF TABLETS 4 MAJOR TYPES | / TABLETS ORALLY GIVEN INGESTED THROUGH | TABLETS OTHER ROUTES TABETS FOR TABLETS TO PREPARE SOLUTIONS ORAL CAVITIESORALLY INGESTED TABLETS | Compressed Enteric Coated tablets Tablets Multiple = Film Coated Tablets Sugar Coated Tablets | Chewable Tablets |Majority of the tablets are ingested orally. These tablets are swallowed intact along with a sufficient quantity of water. Compressed tablets — prepared by compression f powdered crystalline or granular materials, by the application of high pressures using punches and die. They do not contain any special coating. Here rapid disintegration occurs which releases the drug rapidly. «Multi - compressed tablets — composed of 2-3 layers. Prepared by introducing the fill material to more than one compression cycle. Multi compression is done in cases where the ingredients are physically or chemically incompatible or when a prolonged action is required, They are further classified into 3 : - compression coated tablets :- layered tablets :- inlay tabletsCompression coated tablets — consists of 2 parts — internal core (the tablet) and surrounding coat. These tablets are prepared by filling coat material to half, core tablet is mechanically transferred, again remaining space is filled with coat material, and finally compression force is applied. Inlay tablets — tablet core is not completed surrounded by the coating, top surface is completely exposed. Prepared by filling the die with coating material and mechanically placing the core in the die, the compressed. Coat is displaced to form the sides. Layered tablets - consists of 2 -3 ingredients in layers. Preferred when 2 or more ingredients have to be administered simultaneously.Coating Core: Compression coated tabletseEnteric tablets — formulated to prevent drug release in the stomach. Such an enteric coating is preferred when the drug gets inactivated or destroyed by gastric pH, or when drug is irritating to the gastric mucosa. Enteric coat is insoluble in the acidic pH and soluble in the alkaline pH. Such tablets are also meant for delayed release. Enteric coating materials — polymers like Cellulose acetate phthalate, hydroxypropylmethylcellulose. eSugar coated tablets — contain concentrated sugar solution coating. Used to improve _ patients compliance, increase physical appearance, mask unpleasant taste, increase the stability or modify the release of the drug.Enteric-coated drugs do not dissolvein the eng Suen Le ad ofthe small intestine NAOT ey Enverie coating bayer ani eredeFilm coated tablets — are tablets coated with a thin layer of polymer material or a mixture of polymer materials. The coating is designed to break the core tablet at the desired location in the GIT. Film coating also protects the tablet from atmospheric effects. eChewable tablets -— are chewed prior to swallowing, useful for children or adults who have difficulty with swallowing the tablet intact. Substances like mannitol, dextrose are used in the preparation along with the active ingredient. These tablets do not require any disintegrating agents. They should also have an acceptable taste and flavour.| TABLETS FOR ORAL CAVITIES Lozenges and Troches Buccal and Sublingual Tablets Dental ConesOral cavity includes lips, cheeks, teeth, gums, floor of the mouth, bony roof of the mouth, and two thirds of the tongue. éeBuccal and Sublingual tablets — small and flat oval tablets. _ Sublingual administration — placing drug under the tongue to dissolve and absorb into the blood. Buccal administration — placing a drug between gums and cheek to dissolve and absorb into blood eLozenges and troches— disc shaped with medicinal agents incorporated in flavoured hard candy or sugar base. Intended to be dissolved slowly in the oral cavity «Dental cones - are compressed tablets which are placed in the empty sockets after tooth pytrartinn tr nreveant attarkl naff harteama nrDental Cones[ TABLETS GIVEN BY OTHER ROUTES Vaginal tablets Implantation TabletseImplants — long acting sterile tablets which are designed to provide continuous release of drugs for the months or a year. Placed under the skin or inserted subcutaneously by means of minor surgical operation. Implants must be sterile. Packed individually in sterile conditions. Contains rate controlling excipients. Mainly employed to administer hormones. °Vaginal Tablets — uncoated bullet shaped or ovoid tablets. They are designed to dissolve slowly in the vaginal cavity. Used to release medicaments to provide local pharmacological effect and for systematic absorption.| TABLETS TO PREPARE SOLUTIONS —_ | Effervescent Dispensing Tablets tablets Hypodermic Tablet Triturates / Tablets Moulded TabletseEffervescent tablets — uncoated tablets that contain the following — active ingredient, _ organic acids (eg. tartaric acid), and sodium | bicarbonate. When dropped into water, tablet reacts with water releasing carbon dioxide, producing effervescence leading to disintegration. eDispensing Tablets — contain large amount of highly potent active pharmaceutical ingredients. They should be added to given volume of water. Great care should be taken in packaging and labelling. These tablets are readily dispensed into liquids.eHypodermic tablets — soft readily soluble tablets. Tablets composed with drugs that are water soluble and they are _ dissolved in sterile water or water for injection, and administered via parenteral routes. eTablet triturates— small cylindrical molded or compressed tablets. They usually contain a potent drug mixed with excipients like lactose, sucrose or any other suitable diluent. Prepared in special moldsEffervescent ADICTS | Hypodermic Tablets | ( Mold for Tablet Triturates }EXCIPIENTS Pharmaceutical Excipients :- are substances other than the pharmacologically active drug or pro -drug which are included in the manufacturing process or are contained in a finished pharmaceutical dosage form. Helps the drug to exert its action at the required location. «Also it keeps the drug from being released early. eSome may help in protecting the product stability, taste better, look better, improve patients compliance and also to break into smaller pieces.ANTI- OXIDANTS TYPES OF nites = DISSOLUTION RETARDANTSDILUENTS v Also known as fillers or bulking agents. v Use for making up of required bulk for a tablet. “Mostly used when dose of drug is too small to _ formulate as a tablet. If the dose is high, bulking agents are avoided. vProperties of an ideal diluent :- physiologically inert, non toxic, physically and chemically stable, easily available, free from microbial contamination, and does not affect the bioavailability of drug. “Diluents can be of the following types:- lactose, spray dried lactose, mannitol, dextrose, starch, sorbitol, sucrose and microcrystalline cellulose.eLactose — Most widely used Diluent. Available in the hydrous and anydrous form. Preferred because of pleasant taste, readily dissolvable in water, low cost and less disintegration time. One disadvantage is that it undergoes discolouration when in contact with amine drugs eSpray dried lactose — can be used for direct compression due to its cohesive nature and good flow characteristics. In presence of moisture, they may undergo darkening. eMannitol — widely used as a diluent in chewable tablet. It is non-hygroscopic and non- carcinogenic. But mannitol is expensive.eDextrose — Available in the hydrous and anhydrous form. When combined in a certain amount with spray dried lactose, darkening of spray dried lactose can be avoided. eStarch — very occasionally used diluent for tablet manufacturing. USP grade of starch can be used due to its free flowing nature and direct compressibility. eSucrose — suitable for direct compression. eMicrocrystalline cellulose — two main grades are available but they are expensive, so used in combination with other diluents.BINDERS vOne of the most important excipient in tablet formulation. _ ¥Also called as Adhesives. _ vWhen mixed with powders, they are used to produce granules. vEnhance the free flowing capacity of granules of desired sized and hardness. v Selection of binder depends on the type of tablet. vFor eg. lozenges require more amount of binder whereas tablets require less. ¥Binders can be of the following types:- gum acacia, tragacanth, starch paste, sucrose solution, polyvinylpyrolidine, gelatin, celluose derivatives — HPMC, HEC.eGum acacia and tragacanth — used alone in a concentration of 10-25% or in combination. eGelatine — should be prepared fresh and added in warm condition to avoid solidification. Starch paste — is prepared by dispensing starch into cold purified water, warming the mixture by continuous stirring until a translucent paste is formed. *Sucrose solution — is used a wet binder which is cheap, produces hard but brittle granules. Major disadvantage is the susceptibility to microbial contamination. PVP — used in an aqueous or alcoholic solution. Suitable for moisture sensitive drugs. eCellulose derivatives — natural polymer as binder.LUBRICANTS vAre intended to reduce the friction between the walls of the tablet and walls of the die cavity during / the ejection of tablet. Concentration and time of _ mixing of a lubricant should be optimised. If the concentration is more, mechanical strength of the tablet is reduc; LUBRICANTS SOLUBLE INSOLUBLE LUBRICANTS LUBRICANTSeInsoluble Lubricants — act by inter-crossing the intermediate layer between the tablet material and the die cavity. Such lubricants are intended to act on the tablet surface or on the tablet coating surface, so added in the last stage before compression. *E.g — Calcium or Magnesium stearate, light mineral oil, paraffins ete. eOptimum concentration — 1-4% eSoluble Lubricants — not effective as the insoluble lubricant. eE.g - adipic acid, magnesium lauryl sulphate, sodium lauryl sulphate, polyethylene glycol 4000, 6000, 8000.DISINTEGRANTS vIntended to break up a tablet to smaller pieces _ upon administration, when it comes in contact _ with the gastro intestinal tract. yTablet disintegration is important for the further dissolution of the drug and attaining the drug bioavailability. “Mainly used disintegrants — starch, cellulose and cellulose derivatives. Starch is mainly used due to its cheaper cost, ease of availability, and compatibility with drugs. v Optimum concentration — 5-20%MECHANISM OF DISINTEGRATION e Water uptake through pores e Acts by swelling of disintegrants e Acts by producing gas « Enzymatic actionWater uptake through pores e Water uptake through the pores due to capillary action leads to disintegration. e Hence, hydrophobicity can be a disadvantage for disintegrants using this mechanism. e Maintenance of the porous structure of the drug is also an important factor. eEg -— Starch and _ Microcrystalline celluloseSwelling of Disintegrants e One general problem of such disintegrants is its thickness or forming of a gelatinous mass on contact with water. _e E.g —Acacia and Tragacanth e Optimised concentration should be used, otherwise it may lead to sticking of the powder. Disintegrants that work due to the porous structure and by swelling are called Superdisintegrants - E.g — sodium starch glycolate, sodium glycine carbonate, insoluble cationic exchange resinsActs by producing gas e Used when extra rapid disintegration is required. e Main disadvantage is its stability. When in contact with the slight excess of moisture, it can initiate the reaction. e Stringent control on the environment is required for such type of disintegrants. Enzymatic action e Enzymes are included to act in the presence of water. e E. g—Amylase.FLAVOURS & SWEETENERS vFlavours and sweeteners are added in the _ formulation to mask the unpleasant taste. Added in the concentration — 0.001 — 0.1 % v Dissolved in organic solvents and then the solution is sprayed on the granules just before the step of compression. vNatural sweeteners :- sugar, mannitol, lactose, sucrose v Artificial sweeteners :- saccharin, cyclamate, aspartameCOLOURANTS _ Added to the preparation to make the tablet more aesthetic. v Also used to identify the product. v All colourants used should be approved and certified by the Food and Drug Administration. ¥ Colours are available in two forms : - lakes and dyes vE.g — Eosin Y, Sunset yellow FCF, Yellow orange, Blue green, Burnt sugar.ANTI - ADHESIVES _ vPrevents sticking of the tablet material to the face of the punch or on to the die cavity. VAIl lubricants can be used as anti-adhesives except for water soluble lubricants. vE.g — Talc, Magnesium stearate, Colloidal silicaGLIDANTS Used to facilitate or promote flow of granules from hopper to die cavity by reducing friction between the particles E.g — Tale Optimum concentration — 4-5% Lubricants, Together Glidants called as and Anti —- Antifrictional Adhesives AgentsADSORBANTS vUsually agents that can retain large quantities of liquid | vE.g. — anhydrous calcium phosphate, magnesium carbonate, kaolin BUFFERS v Added to maintain a required pH. vE.g — sodium bicarbonate, sodium citrate ANTIOXIDANTS v Added to protect drug from oxidation v Anti-oxidants undergo oxidation instead of the drug vE.g — ascorbic acid, sodium bisulphiteCHELATING AGENTS ¥Tend to form complexes with trace amount of _ heavy metal ions that can initiate oxidation by _ theor catalytic activity vE.g. — ethylenediamine tetraacetic acid {EDTA}, citric acid PRESERVATIVES vPrevents the growth of microorganism that can lead to contamination vE.g — parabens like methyl paraben, propyl parabenDISSOLUTION ENHANCERS vAlter the molecular forces between the a ingredients to enhance the dissolution process leading to faster therapeutic action vE.g. — surfactants DISSOLUTION RETARDANTS “Incorporated into tablets that are intended for controlled or delayed release. vE.g — waxy materials like stearic acid and their estersTABLETS GRANULATION Tablet Granulation:- is the process in which small powder particles adhere together by forming bonds between them, resulting in the formation of large aggregates called granules. The bonds are formed either by compression or by using binding agents.IMPORTANCE OF TABLET GRANULATION Even though powders are present, granules are prepared due to the following reasons :- ¥ To avoid particle separation in powders, due to their | different size, shape and densities. v Enhance the flow property. Higher flow ability gives better filling of dies or containers. v Granules have higher porosity. v Improves compressibility of powders. v Materials that are hygroscopic may adhere and form a cake if stored as a powder. ¥ Granulation of toxic materials will reduce the hazard of generation of toxic dust, which may arise during the handling of powders.GRANULATION METHODS Granules are used in the manufacturing of Tablets and Pellets. [ GRANULATION METHODS | DIRECT COMPRESSIONIRECT COMPRESSION Dire PREC SS is a dry process where in the powdered material is compressed directly into the tablets without the physical nature of the powder being modified Direct Compression involves the following steps:- vWeigh and grind the ingredients (active ingredients and excipients). y Mixing of active ingredients with powdered excipients including the lubricants and glidants. ¥Compression of mixed powders in a tablet press. ¥ Diluent — spray dried lactose, mannitol v Disintegrants — talc v Lubricants — magnesium stearate ¥ Glidants — tale, colloidal silicaeAdvantages — fewer processing steps, less equipment, less expensive, no involvement of moisture and heat, faster dissolution rate, chance of transfer losses, and lesser equipment contamination. eDisadyantages — selection of excipients is highly restricted due to less inherent binding property in most of the excipients, low dose of drugs will not be uniformly mixed, excipients for direct compression are expensive and they also have a problem of interaction with drug substances.WET GRANULATION Wet or Moist granulation is the most conventional, versatile, and widely used techniques for the manufacture of compressed tablets. This technique involves the usage of liquid to form compact masses. Wet granulation involves the following steps:- “Weigh, sift and mix of drug substance and excipients excluding lubricants in an appropriate mixer to get uniform powder mix. vA damp mass is prepared from the powder mix using a binder solution. Insufficient binder causes poor adhesion leading to soft tablets. Excessive binder solution yields hard tablets with slower disintegration rate.v Wet granules are dried in an hot air oven at 60°C. The drying temperature and drying time are carefully observed. vDried granules are passed through Sieve 20 to get uniform size granules. v Appropriate amount of lubricants is mixed with granules. The remaining amount of disintegrants are also added at this stage, v Mixed granules are compressed in a single or multi- punch station tablet press fitted with appropriate punches and dies.«Advantages — produce more spherical granules, have better flow property, useful for low compressibility drugs, ensures better content uniformity in case of low dose drugs, improved compressibility, suitable for hydrophilic drugs. eDisadvantages — several steps are involved, time, labour, energy, equipment and space required for the process is more, not suitable for hydrophobic, thermolabile and moisture sensitive materials, water used as solvent can affect the drugs stability causing hydrolysis, drying time is longer, increased length of processDRY GRANULATION Dry or Double compression is used to form granules without using a liquid solution because the | product to be granulated may be sensitive to moisture and heat. The techniques of dry granulation of powdered material can be accomplished by two methods :- |. Slugging — formation of extra large tablets first, then broken into granules, which are again recompressed. 2. Roller compaction method — achieved by feeding powder through a set of directly opposed counter rotating rollers.Dry granulation involves the following steps:- “Appropriate quantities of ingredients and excipients are weighed on an analytical balance. “Ingredients are mixed in a powder mixer until a uniform powder mix is achieved. The half quantity of lubricant is added at this stage to enhance powder flow and to prevent sticking of powder to die. “Mixed ingredients are compressed into flat large tablets called slug. This is called pre-compression or slugging. “Slugs are broken into smaller pieces using an appropriate miller, Milled slugs are sieved to produce uniform granules. “After sieving, remaining lubricants and excipients are incorporated into granules and mixed to form a uniform blend. “Mixed uniform blend of granules are compressed into tablet using the tablet press.eAdvantages — requires less equipment and minimum floor space, suitable for moisture and heat sensitive materials, no alteration in drug morphology during formulation, shows better disintegration as dry binder has lesser adhesive effect. eDisadyantages — process generates dust which can cause cross contamination, separation of components may occur after mixing, flowability of powder decreases .Step! Step-2 Step-3TABLET COMPRESSION MACHINES Dried granules are compressed into tablet _ using machines known as Tablet Compression / machines or Tablet Press. | TABLET COMPRESSION MACHINES | SINGLE PUNCH DRY COTA TABLET TABLET MACHINE MACHINE MULTI STATION ROTARY PRESSv Tablet presses are designed with following basic components. | vHopper_- holds an feed granules to be compressed. v Dies _- define size and shape of tablet vPunches — compresses granules within the dies. vCam_ Tracts — guides the movement of punches ¥Feeding Mechanism — moving mechanism of the granules from the hopper to the dies.4 f 4’ 4 HOPPER | PUNCHES & DIES | & DIESSINGLE PUNCH TABLET MACHINE Also called as ECCENTRIC PRESS. Ideal for Small Scale Productions. This tablet press includes a Die and a pair of Upper and Lower Punch, along with the basic components. Also the machine has two more components :- ¥Capacity Regulator — adjusts lower punch to allow the required quantity of granules by the die. vEjection Regulator — facilitates ejection of tablet from die cavity after compression.— manual driving whee! cylindrical gearing — f cam gearing belt gearing feed shoe electric motor. ‘core componentsWORKING OF SINGLE PUNCH STATION ¥ The upper punch moves up and lower punch moves down to create a cavity in the die. v Feed or granules from the hopper fall into the dies. Upper punch moves down ~- compresses the granules into tablets v Upper punch moves up, lower punch also moves up — eject the compressed tablet. vyWhole process repeats again and again, until granules finishes. v Output — 200 tablets per minute vUses high pressure to compress tablet to reduce weight variation between tablets.SSSssssg = i adMULTI STATION ROTARY PRESS Multistation rotary presses are termed as “rotary” because the head that holds the die, upper _ and lower punches in place — Rotates. As the head rotates, the punches are guided up and down by fixed cam tracts. The portion of the head that hold the upper punches are called upper turrets, and the portion that hold the lower punches are called lower turrets. The portion holding the dies are called die table. Along with the basic components, additional components are, » Ejection cam — facilitates ejection of tablet from die »Take off blades — helps to push tablet to a discharge chute, which is collected in a container.WORKING OF MULTISTATION ROTARY PRESS ¥ The powder or granules are placed in the hopper. ¥ Material is fed into several dies simultaneously. vMachine removes excess of powder to avoid any form of inconsistencies. vDesired volume and weight of powder is compressed to tablets. vUpper and lower punch exert a predetermined amount of pressure that compresses the tablet. v As the head revolves, dies get filled with granules flowing from the hopper. vGranules are compressed when the upper and lower punch comes close together.¥The upper cam pull the upper punches back to the initial position and the lower punches are lifted up _ to eject processed tablets out of the die cavity. vScraper will remove the tablet from compression machine. vThis is then considered, as the end of one compression cycle of the tablet compression machine v Output — 1200 tablets / minute. v Used for large seale production.DRY COTA TABLET MACHINE Here, two rotary machines work simultaneously, therefore, core tablet is prepared in one machine, and then transferred to the another machine for compress coating. » Preferred for multicompressed, multicoloured and press coated tablets »Allow manufacture to manufacture a wide variety of tablet shapes.EQUIPMENT TOOLING Equipment tooling:- The size and the shape of a tablet, and certain identification markings are determined by the equipment tooling or compression machine tooling. °Each tooling set consists of die and upper and lower punches. °Tooling must meet the requirements to satisfy the needs of dosage uniformity, product efficiency and aesthetic appearance.Basically, there are two types of equipment tooling or compression machine tooling. | EQUIPMENT TOOLING | | proounc | {se tooLineEQUIPMENT TOOLING. mee “ER Die Dinwder DIEPARAMETERS Compression force exerted by the machine on the tools Barrel diameter of the Punch Head diameter of the Punch Length of the Punch Die Diameter D TOOLING 10 tonnes 1 inch 1.25 inch 5.25 inch 0.945 inch BB TOOLING 6.5 tonnes 0.75 inch 1 inch 5.25 inch 1.18 inchSeveral types of steel are normally used for the manufacture of compression machine tools. Steel differs in toughness to withstand the compressing forces and wear resistance. Therefore, selection of the steel must be based on experience and accumulated history of the product to be manufactured. “Improper storage and handling can readily result in damage and lead to the complete replacement of the whole set of punches and dies. vPunch tips are delicate and susceptible to damage, if they come in contact with each other or with the dies, or due to improper handling while insertion and removal of the punches and dies. ¥To avoid tooling damage, calculate the load or pressure to be applied before the production starts.COMPRESSION & PROCESSING PROBLEMS An ideal tablet should be free from any _ visual or functional defect. Number of problems can be encountered during the tablet manufacture process. vVisual defects :- due to inadequate fines or moisture in granules or faulty machine settings. They can be further due to the following factors :- formulation design, tabletting process, machine related, or others. “Functional defects :- due to a faulty formulation calculation.CAPPING & LAMINATION PROCESS RELATED CHIPPING & CRACKING PICKING & STICKING VISUAL FORMULATION WEIGHT & DEFECTS RELATED HARDNESS VARIATION MOTTLING DOUBLE IMPRESSION MACHINE RELATED1, CAPPING & LAMINATION Capping — partial or complete separation of top or bottom crown of the tablet from the main body of the tablet Lamination — separation of the tablet into 2 or more distinct layers. Capping & lamination occurs due to the following reasons:- Presence of excess fine powders will lead to entrapment of air in the tablet during compression . This air has a tendency to come out leading to cappig and lamination. Quantity of fine incorporated should be optimised to correct the problemv Worn out punches and dies also cause capping and lamination. Hence, replacement of the punches are required. Chromium plated dies can be used to correct the problem. “High pressure also an be used, which can be optimised before the production starts. vInsufficient or improper lubricant can cause this problem, hence the amount of lubricant used can be optimised or the type of lubricant can be changed. ¥Addition of oily or waxy materials can cause capping and lamination, that can be corrected by the usage of adsorbents or absorbents. v Over drying of granules are also a major reason for capping and lamination to occur. This can be overcome by the addition of optimum level of moisture.Lamination Good tablet2. PICKING Picking — material gets off from the tablet surface and adheres to the face of the punch. Reasons :- ~ When punches have letters with sharp edges like A, B, M, W etc. v When granules are improperly dried. v When materials have low melting point. Corrections :- y punches that have sharp edged letters can be corrected by modifying the design of letters. y¥ When using low melting point materials, punches should be polished with colloidal silicaras NA 43. STICKING Sticking — material gets off from the tablet surface and adheres to the die wall. Reasons :- ¥ Presence of excess moisture. v Improper lubrication of granules. v Fast compression process. Corrections :- v Proper drying of granules. ~The amount of lubricant used can be optimised or the type of lubricant can be changed, v Speed of the compression process should be optimised ¥ Dies should be polished with colloidal silicacal / 4. MOTTLING _Mottling :- is a defect that occurs with coloured tablets. 5 Gal y Mottling occurs due to the uneven { i distribution of the colour on the surface St of the coloured tablets. Reasons :- Migration of the dye on the tablet surface during the process of drying _~ Decomposition of active ingredient or excipients improper mixing of colour binder salution | Corrections :- _» Change the solvent system and decrease of temperature while drying. _¥ Incorporating dry colour excipients and | fine powdered adhesives during mixing step of ingredients. Then the granulating q liquid is added to prepare granules.5. CHIPPING Chipping :- is a defect where the film on the edges of the tablet is chipped or dented. Reasons :- ¥ Dry granules ~ Addition of large amount of binder ¥ Worn out edges of the punch Corrections :- ¥ Addition of hygroscopic substances * moisten the granules. ¥ Polishing of edges of punch. ¥ Optimisation of the amount of binder.6. CRACKING Cracking :- is a defect where upper and lower central surface of tablets gets cracked, Reasons :- v Dry granules y Size of granules are too large, air can get entrapped between the cavities, and during compression cracking occurs. ~ Deep concave shaped punches Corrections :- ¥ Addition of right amount of binder moistening the granules. ¥ Reduce granules size or add fines.7. DOUBLE IMPRESSION Double impression — is a defect where the shape of the monogram or _ other engravings appears stamped twice on the tablet. Reasons :- y Due to the free rotation of the lower punch. The lower punch moves slightly upward before the ejection of a tablet and makes new impression on the bottom of the tablet Corrections :- y Control the free rotation of any punches8. WEIGHT VARIATION | Weight variation— occurs when tablets compressed do not have uniform weight. Ratholing ~~ Reasons :- ~~ «When granules are not in uniform size. This changes the filling of granules in the die. Large size or too small size granules changes can hence cause | weight variation. ~ Poor flow of granules from the hopper to the die. Rat holing, where the powder gets deposited over the inner walls of the hopper, this obstructs the flow of powder from the hopper to die. _ Correetions :- ¥ Addition of vibrator to the hopper to improve the flow of powder.9. HARDNESS VARIATION Hardness variation— occurs when tablets compressed do not have uniform hardness. Reasons :- v No uniform weight vy Incorrect space between the upper and lower punch at the time of compression Corrections :- v Maintain the weight of the tablet. ¥ Optimum gap between the upper and lower punch should be maintained.a B. TABLET COATINGCONTENTS « Introduction © Types of Tablet Coating * Coating Materials * Coating Composition ¢ Coating Equipments * Tablet Coating DefectsINTRODUCTION Tablet Coating :- is the last critical step in the Tablet Production Cycle. Tablet coating is the process in which the tablet surfaces become covered with a tacky polymeric film to achieve specific benefits. The successful application of coating to tablet provides the visual characteristics for the product, thus the quality of the product may be judged on this final production step.Need of Tablet Coating This additional step of tablet coating in the tablet _ manufacturing process, increases the cost of the product. Therefore, the decision to coat a tablet can be based on the - following reasons :- «Mask unpleasant taste, odour, or colour of a drug. Provide physical and chemical protection for the drug. elmprove pharmaceutical elegance by use of special colours and contrasting printing. Control the release of the drug from the tablet. Protect the drug from gastric environment of the stomach with an acid resistant enteric coating. Incorporate another drug in the coating to avoid chemical incompatibilities or to provide sequential drug release.TYPES OF TABLET COATING 6 MAJOR TYPES ENTERIC poe COATING COATING ELECTROSTATI C COATING DIP COATING VACUUM FILM COATINGSUGAR COATING Sugar coating :- is the process of depositing _ layer that an be either coloured or uncoloured to the tablets. This process is a step wise process. The operator determines :- vthe quantity of the coating solution to add, vthe method and the rate of pouring of coating solution, vwhen to apply the dry air and vhow long or how fast the tablets should be tumbled in the coating pan.The steps involved in sugar coating are :- Sub Syrup Coating Coating1. WATER PROOFING / SEAL COATING Seal Coating :- done to provide moisture barrier to the core tablet and harden the tablet surface. ¥Helps to maintain physical and chemical stability of the finished product. ¥ Materials used in Seal coating :- Shellac , Zein vShellac_ :- effective sealant but it may slow down the disintegration & dissolution time which affects the therapeutic release. ¥ Zein :- an alcohol soluble protein derivative from corn is another effective sealant.Tablets are placed in a coating pan made of stainless steel Rotate the coating pan at the speed of 10rpm with supply of air at 30°C. Three applications of sealing solution {800ml / application} are given 15-20 mints are given for proper drying after each application. Talc is added so that tablets do not stick to each other2. SUB COATING Sub Coating :- applied to round the edges and build up the tablet size. Two methods are used for this sub coating. “Applying a sticky binder solution to the tablets followed by dusting of sub coating powder and then drying. This is repeated until the desired size is achieved. Sub coating powders include :- calcium carbonate, powdered sucrose, powdered dry gum acacia. v Another method, is the spraying process, where a sub coating powder suspension containing both the binder and the insoluble powder is sprayed intermittently on the tablet bedTurn heat and inlet air off. Use only exhaust system Rotate the coating pan at the speed of 10rpm Use 1.5 litres of sub coating solution and apply 3-9 coats to the tablets. Thickness is checked volumetrically. 15-20 mints are given for proper drying after each application. Apply sub coating powder until tablets roll freely and show no signs of stickiness. After last coat, jog the pans periodically for at least 2-4 hours to ensure dryness.; : 3. SYRUP COATING or SMOOTH COATING Syrup coating or Smooth Coating :- done to cover and fill the imperfections in the tablet surface caused by the sub coating step, so as to increase the tablet dimension to a predetermined level. “Several coats of simple syrup solution (60- 70%) are applied. v Syrup solution contains pigments, starch, gelatin, or acacia. v Syrup solutions are also called grossing syrups.Remove excess dust in the coating pan. Turn on the exhaust inlet air with a temperature of 45-48°C. Rotate the coating pan at the speed of 12rpm Apply 5-15 coats of grossing syrup. Since this solution dries off quickly, uniform rapid distribution is provided The process is done until specific tablet volume is required, and then turn off the heat.4, COLOURING Colouring :- gives colour an finished size of the tablet. ’A thin sucrose solution containing the requisite colouring materials is used for the process. ¥ Water soluble dyes or water insoluble pigments can be used. vy Water insoluble dyes are preferred over water soluble dyes as water soluble dyes may cause mottling.Rotate the coating pan at the speed of 12rpm 3-4 coats of regular coloured syrup is applied rapidly. | Turn off the heat with no supply of air, The last coat should be syrup solution without colour and allow to dry overnight.5. POLISHING Polishing :- Tablets after colouring, they are polished to give desired luster to the tablet. yPolished by carefully applying, powdered wax { beeswax or carnauba} or warm solutions of these waxes in naphtha or suitable volatile solvents.Cleaned canvas lined coating pans are used. Air is supplied with exhaust air. Turn off heat and rotate coating pan at speed of 12rpm. Apply 3 - 4 coats of warm polishing solution, approximately 300mi per application. Let the solvent evaporate between each coatsCompressed core U Sealing U Subcoating and smoothing © UL, Coloured coating Polishing / ~~FILM COATING Film coating :- is the process of placing a thin, skin tight coating of plastic like material or polymer over the compressed tablet. Film coating solutions can be non — aqueous or aqueous. Volatility of the solvent enables the film to adhere quickly to the surface of tablets,laeal Characteristics of a Film Coating Material y Adequate solubility in coating solvent and in the GI fluid. Stability in presence of heat, light, moisture, air, etc. y~Compatibility with addictives present, non — toxic, inert, resistant to cracking, withstand normal handling. vy Compatibility to obtain a elegant product. vEase of printing procedure on high speed equipment.Film Coating Materials » Film formers ¥ Alloying substance v Solvent system v Plasticizer v Opaquant extenders ¥ Colourants ¥ Glossants v Anti — Oxidants v Flavours & Sweetners v Surfactants v Anti — Microbials1. FILM FORMERS Capable of producing smooth thin film reproducible under conventional __coating conditions and applicable to variety of tablet shapes. oPolymers are mainly used as film formers. oK.g — cellulose acetate phthallate, hydroxy propyl methyl cellulose, sodium carboxy methyl cellulose.2, ALLOYING SUBSTANCE oProvides water solubility or permeability to the film to ensure penetration by body fluids and therapeutic availability of the drug. oE.g — polyethylene glycol3, SOLVENT SYSTEM ols mainly used for the dissolving of solvent and to allow the spread of other components over the tablets while allowing rapid evaporation to permit speedy operation. oE.g —- ethanol, methanol, chlorinated hydrocarbons, methylene chloride.4, PLASTICIZER oGives elasticity and flexibility to the coat material that increases the durability. Plasticizers act by breaking down the polymer — polymer bond and reducing the films brittleness. oE.g — castor oil, propylene glycol, polyethylene glycol.5. OPAQUANT EXTENDERS oAdded to give more pastel colours and enhance film coverage. E.g — titanium dioxide, tale, magnesium carbonate. 6, COLOURANTS oAdded to enhance visual appeal of the product and identify the product. oE.g — sunset yellow, tartrazine, erythrosine.7. GLOSSANTS oAdded to give luster to the tablet without polishing. oE.g — beeswax. 8. ANTI - OXIDANTS oAdded to stabilize a dye system. oE.g — oximes, phenols.9, FLAVOURS & SWEETNERS oAdded to mask unpleasant taste and odour. oE.g — aspartame, water soluble pineapple flavour. 10. SURFACTANTS oAdded to solubilise insoluble ingredients in the coating. oE.g — spans and tweens. 11. ANTI - MICROBIALS oAdded to prevent microbial growth in coating composition. oF.g — alkylisothiazolinone, carbamates.ENTERIC COATING Enterie coating :- is the process of coating done to the tablet to protect from the acidity of stomach and usually disintegrate the tablet in the intestine. Reasons of Enteric Coating :- v Protect acid labile drugs from GI fluid. vPrevent gastric distress or nausea due to irritation from a drug. vDeliver drugs intended for local action in the intestines. vDeliver drugs that are optimised to absorb in the small intestine. v Provide delayed releaseIdeal Characteristics of a Enteric Coating Material y Resistant to gastric fluids v Ready susceptibility or permeability to intestinal fluids. ¥ Compatibility with coating solutions. ¥ Formation of continuous film YNon toxicity, low cost, ease of application Enteric coating materials :- cellulose acid phtahllate, shellac and its derivativesELECTROSTATIC COATING Electrostatic coating :- used to apply coat conductive substances. v Coating material contains conductive ionic species of opposite charge is sprayed on to the charged substrate.DIP COATING Dip coating :- coating is applied to the tablet cores by dipping them into the coating solution. v Wet tablets are dried in an conventional manner in coating pansVACUUM FILM COATING - Vacuum Film Coating :- is a coating procedure that employs a specially designed baffled pans. v Pan is water jacketed. v Sealed to achieve a vacuum system. v Tablets are placed in the sealed pan. ¥Coating solution is then applied to tablets with an airless spray system.TABLET COATING MATERIALS The coating materials is a physical deposition of the material on the tablet substrate, or they form a continuous film with a wide variety of properties depending on the composition of the coating formulations. | Examples of physical deposition of the coating materials are the techniques of sugar, shellac, wax or polymer coatingsCoating Materials Hydroxypropyl methylcellulose USP {HPMC} Methyl hydroxyethyleellulose {MHEC} Hydroxypropylcellulose {HPC} Ethylcellulose {EC} Sodium carboxymethylcellulose {Na CMC} Povidone USP Polyethylene glycol {PEG} Acrylate polymers Polyvinyl acetate phthalate {PVAP} . Cellulose acetate phthalate {CAP} HPMC Phthalate1, FYDROXAYPROPYL METHYLCELLULOSE USP oPrepared by reacting alkali treated cellulose with methyl! chloride to introduce methoxy groups and then react with propylene glycol ether groups oAvailable in different viscosity grades Soluble in GI fluid and other solvents. oCauses no change in disintegration and bioavailability. Stable in presence of heat, light, moisture or air Easily able to incorporate or other addictives.2. METHYL HYDROXYETHYLCELLULOSE Prepared by reacting alkali treated cellulose with methyl! chloride to introduce methoxy groups and then react with ethylene oxide. Available in different grades Structural similarity of MHEC with that of HPMC, shows that MHEC shares the same properties of HPMC.3. HYDROXY PROPYLCELLULOSE oPrepared by reacting cellulose with sodium hydroxide and then react with propylene oxide at an elevated temperature and pressure. Yield flexible films oSoluble in water below 40°C, GI fluid, polar organic solvents. oUsually used in combination with other polymers4. ETHYLCELLULOSE oPrepared by reacting ethyl chloride or ethyl sulfate with cellulose dissolved in sodium hydroxide. »Available in different viscosity grades olnsoluble in water below 40°C & GI fluid. Hence, used in combination with a water soluble addictives. oUnplasticized EC films are brittle and require film modifiers to obtain an acceptable film.9. SODIUM CARBOXY METHYLCELLULOSE Sodium salt of carboxymethylcellulose Prepared by reacting soda cellulose with sodium salt of monochloroacetic acid. Available in different viscosity grades Insoluble in organic solvents but soluble in water to form colloidal solutions. oFilms are brittle but adhere well to the tablets.6. POVIDONE USP Synthetic polymer consisting of linear 1-vinyl 2- pyrrolidinone groups. oAvailable in 4 different viscosity grades identified with a “K” value — povidone K 15, K30, K60, and K90 oK30 is the most used povidone grade in tablet coating.7, POLYETHYLENE GLYCOLS oManufactured by the reaction of ethylene glycol with ethylene oxide in presence of sodium hydroxide at an elevated temperature and pressure. >PEG of lower molecular weight are liquid at room temperature and used as plasticizer. oPEG of higher molecular weight are white, waxy solids at room temperature and used as a coating material.8. ACRYLATE POLYMERS oAre set of polymers commercially under the trademark EUDRAGIT. oEudragit are available in different forms. EUDRAGIT E :- cationic polymer, which is the only form of eudragit which is soluble in GI fluid. EUDRAGIT RL & RS :- copolymers available only as organic solutions and solid materials. These are mainly used as coating material in delayed release tablets. oEUDRAGIT L & S :- polymers that are mainly used in coating of enteric coated tablets. They are soluble only in pH 6 & pH 7 respectively.9. CELLULOSE ACETATE PHTHALATE oWidely used as enteric coating material. oDissolves only in pH > 6 oHygroscopic, relatively permeable to water and GI fluids oProduces brittle films, hence, combined with hydrophobic film forming materials to achieve a better enteric film.10. POLYVINYL ACETATE PHTHALATE oManufactured by esterification of partially hydrolysed polyvinyl acetate with phthallic anhydride. oMainly used in coating of enteric tablets.11. HPMC PHTHALATE oDerived from HPMC by esterification with phthalic anhydride. ©Dissolve at a lower pH than CAP or Acrylate polymers, hence can increase the bioavailability of some drugs.TABLET COATING COMPOSITION The basic or starting composition of a tablet coating is Wr _ obtained from the past experience or various sources of literature. The composition of a tablet coating material includes :- ~ Coat or film formers v Alloying substance v Solvent system vPlasticizer ~ Opaquant extenders ~Colourants ~Glossants v Anti — Oxidants Flavours & Sweetners » Surfactants v Anti — Microbials| TABLET COATING EQUIPMENTS Most of the tablet coating process uses one of the following 3 major types of equipment | 3MAJORTYPES FLUIDIZED BED CONVENTIONAL COATING PAN COATING PAN PERFORATED COATING PANFLUIDIZED BED COATING PAN «Highly efficient coating systems «Mainly consists of a vertical chamber Tablets are first filled into the vertical chamber — this process is called Charging. +Fluidization of tablets are achieved by upward flow of air. Air stream first enters the column which causes the tablets to rise in the centre. + Tablets then fall towards the chambers wall «Then the tablets move downwards to enter the air stream again. Coating solutions are applied through spray nozzles that are kept at the top or bottom of the vertical chamber.‘Screen/Process Air Distribution PlateCONVENTIONAL COATING PAN The standard or conventional coating pan system consists of a circular metal pan mounted on a stand, tilted to an angle of about 45°C. The pan is about 8-60 inches in diameter and is rotated on a horizontal axis by a motor. The coating pan has a provision of hot air through an inlet port. The heated air is directed into the tablet bed and leaves through an exhaust duct. «Temperature of the hot air is maintained, so that the chemical constituents are not degraded or decomposed. Coating solutions are applied by ladling or spraying the coating material on to the tablet bed. «Spraying produces more faster and even distribution of the coating solution.INLET AIR SUPPLY EXHAUST TABLET BED [ General Diagram of Standard Coating PanTo increase the spraying efficiency, conventional coating pans were modified into three :- | CONVENTIONAL COATING PAN | IMMERSION TUBE IMMERSION SWORD SYSTEM SYSTEM PELLEGRINI SYSTEMIMMERSION TUBE SYSTEM Aan ein this system, a tube is ~~ immersed in the tablet bed, oe “The tube delivers the heated idl air, and a spray nozzle is built in pray the tip of the tube . «During this operation, the coating solution is applied simultaneously with the heated air from the immersed tube. «Heated air flows upwards and leaves the system by the exhaust duct. *This enhances the drying efficiency.Immersion Tube SystemIMMERSION SWORD SYSTEM sin this system, a perforated _ sword is immersed in the tablet bed. The perforated sword delivers the heated air. During this operation, the coating solutions are applied by an atomised spray system directed to the surface of the rotating pan. Heated air flows upwards from the sword through the tablet bed -and leaves the system by the _ exhaust duct. This enhances the drying efficiency.Immersion Sword SystemIn this system, baffled _ plates and diffusers are present.Conventional Coating Pan with Baffles Baffles ‘Tapered side wall Spray —_lPERFORATED COATING PAN In this system, all equipments of this type, consists of perforated or partially perforated drum that is rotated __ on its horizontal axis in an enclosed housing. *Drying air is applied to the tablet bed through different ways in different types of perforated coating pans, «In all the types of perforated coating pans, the coating solutions are applied to the surface of the rotating tablet bed through spraying nozzles that are positioned inside the drum. Perforated pan coaters are efficient drying systems with high coating capacity, and can be completely automated for both sugar coating and film coating processes.To increase the spraying efficiency, perforated coating pans were modified into four :- | PERFORATED COATING PAN | ACCEL GLATT COATER COTA SYSTEM SYSTEM | HI - COATER PAN | DRIA COATER PAN | SYSTEM SYSTEMACCELA —- COTA SYSTEM “Baffles — freely mix tablets within drum when rotating. Spray gun — atomizes coating solution. «Drying air directed into the drum, is passed through the tablet bed, and is exhausted through perforations in the drum. Process is fast and drying efficiency is also good.HI - COATER SYSTEM E «Drying air directed into the drum, is passed \ amy through the tablet bed, and is exhausted through (— perforations below the coating drum. ~__. This decreases the coating time. Ai SUPPLY TABLET BED PAN wir PERFORATED PLATES.DRIA - COATER SYSTEM «Drying air is introduced through hollow perforated As the pan rotates, the ribs dip into the tablet bed, and _ drying air passes up through and fluidizes the tablet bed. Exhaust is from the back of the pan.Ci GLATT COATER SYSTEM «Drying air can be directed from inside the drum a through the tablet bed and out an exhaust duct, (alternatively with an optional split chambered plenum. ~____ * Several airflow configurations are possible.TABLET COATING DEFECTS mee Eee are >_> = — _ a esBLISTERING «An un-smooth coated surface shows a _ number of uneven spots called blisters. | = Causes — effect of temperature on the strength, elasticity and adhesion of the coat. Remedy — use mild drying condition. as‘s — excessive attrition during coating. — increase hardness of film.CRATERING «Defect of film coating where volcanic like craters appears exposing the tablet surface. _ + Causes — penetration of coating solution into the _ surface of the tablet. «Remedy — decrease in spray application rate - use of optimum drying.STICKING & PICKING | *Defect where isolated areas of films are pulled _ away from the surface when the tablet sticks together and then part. Le iTWINNING «Two tablets stick together. _ «Causes — improper evaporation of coating _ solution. «Remedy - reduce spray rate and increase coating pan speed.BLOOMING «Coating becomes dull immediately or after prolonged storage. Causes -— using low molecular weight ' plasticizer. «Remedy — increase molecular weight and concentration of plasticizer. Sa oa Dull coatBLUSHING Defect where white specks are precipitated on the film «Causes — excessive high coating temperature “Remedy — decrease drying air temperature.COLOUR VARIATION “Either individual tablet colour variation or whole batch colour variation. Causes — improper mixing, uneven spray attern, insufficient coating, mottling of dyes, plasticizer ete. «Remedy — use of lake dyes eliminates mottlin, reformulation with different plasticizer and other addictives.— improper formulation, poor logo design, improper application of coating solution, improper atomization pressure, high viscosity of coating. — addition of alcohol to polymer solution increases dispersion.ORANGE PEEL «A surface defect resulting in the film being rough and non - glossy. Appearance is similar to that of a peeled orange Causes — inadequate spreading of coating solution before drying, high solution viscosity «Remedy — use mild drying conditions, addition of solvents to reduce viscosityCRACKING «Small fine cracks observed on the upper and lower central surface of tablets Causes — use of high molecular weight polymers, high internal stress Remedy — use low molecular weight polymers or polymeric blends.CONTENTS « Non — Official Tests of Quality Control of Tablets * Official Tests of Quality Control of TabletsINTRODUCTION In Process Quality Control tests are routinely run to monitor the compression and manufacturing process. Quality Control Tests are generally divided into two :- 1. Non — Official Tests 2. Official TestsNON —- OFFICIAL TESTS GENERAL APPEARANCE TESTS SIZE & IDENTIFICATION SHAPE MARKINGS ORGANOLEPTIC PROPERTIESGENERAL APPEARENCE *General appearance of a tablet is essential for consumers acceptance, for control of batch to batch uniformity, or tablet to tablet uniformity. This involves the evaluation of :- size, shape, colour, odour, taste, surface texture, physical flaws, consistency, and legibility of identification markings.1. SIZE & SHAPE eShould dimensionally described, monitored and controlled. eThickness of the tablet may be measured using micrometer, or sliding caliper scale . °Physical dimensions control the weight of the tablet.Measuring Faces For Inside Measurement Gide Scale SLIDING CALIPER SCALEll. IDENTIFICATION MARKINGS Manufacturing companies use unique markings on the tablet, in addition to the colour used :- rapid identification of the product. eIdentification markings include ;:- symbols, company name, product code, product name, or product potency eTherefore markings on the tablet should be evaluated for a quality product.II. ORGANOLEPTIC PROPERTIES eUniformity of the colour must be achieved within the batch of tablets. Non —uniformity of the colour shows a poor product. ePresence of odour in a batch of tablets could indicate a stability problem, such as poor smelling odour in aspirins, if acetic acid in the tablet degrades. However, presence of odour in some tablets could be a character of the tablets, such as flavourful odour in vitamin tablets. °A tablet level of defects such as chips, cracks, contamination from foreign substances (presence of hair, oil droplets, or dirt), surface texture (smooth or rough), appearance (dull or shiny) should be evaluated — should be zero defect.OFFICIAL TESTS 9 TYPES | = CONTENT HARDNESS UNIFORMITY % WEIGHT GAIN FRIABILTY IN COATED TABLETS WEIGHT THICKNESS OF VARATION TABLETS API % TEST DISSOLUTION TEST TEST FILM IN COATEDHARDNESS TEST eTablets require a certain amount of strength or _ hardness during transportation and handling. eGenerally, greater compression force is applied, harder the tablets, Certain tablets such as lozenges or buccal tablets are intended to dissolve slowly, so they are made intentionally hard. eFor tablets meant for immediate release, they are intentionally made soft. «Tablets should be sufficiently hard to resist breaking during normal handling and soft enough to disintegrate properly after swallowing,APPARATUS 1- MONSANTO HARDNESS TESTER eThis apparatus has a spring, screw knob, and a graduated scale. eThe reading on the graduated scale is adjusted to zero. The tablet to be tested is placed between the anvil and spindle . eThe screw knob moves forward until the tablet breaks. «Note down the reading on the graduated scale, which indicates the force required to break the tablet. The force is measured in kilograms.TABLET SPINDLE GRADUATED SCALEAPPARATUS I1- PFIZER TESTER The tablet to be tested is placed between the jaws of the apparatus. The reading on the pressure dial is adjusted to zero. Then the press the plier like handle with hands. eReading on the pressure dial is noted which indicates the force required in kilogram or pound — which is the force required to break the tablets.PLIER LIKE PRESSFRIABILITY TEST eDone to check the ability of a tablet to break into smaller pieces under pressure, mechanical shock, or stress during handling and transportation. Strength of the tablet plays an important role in the dissolution and disintegration of the tablet. eAfter the friability test, tablets are inspected for breakage and the percentage of tablet mass lost through chipping.APPARATUS — ROCHE FRIABILATOR eConsists of a drum or plastic chamber having diameter 283-291mm and a depth of 36-40mm. Rotation speed of drum is 25rpm, *Carefully weigh 20 tablets and place them in a plastic chamber and rotate it for 4 minutes or set 100 number of rotations. «During each revolution, tablets fall from a distance of about 6 inches. After 100 revolutions or 4 minutes, remove the tablets from the chamber. Dust the tablets and reweigh the tablets. °Percentage weight loss is calculated. elf there is a loss in weight, this indicates friability. sLoss of 0.5-1% of the weight is considered acceptable.WEIGHT VARIATION TEST 20 tablets are randomly selected and weighed individually. «Average weight of the 20 tablets are also calculated. eIndividual weight is compared with the average weight. *Not more than the individual weight of two tablets may deviate from the average weight, by more than the percentage deviation. T AVERAGE WEIGHT PERCENTAGE 80mg or less 10 8-250mg 7S 250mg or more | 5CONTENT UNIFORMITY TEST eAccording to United States Pharmacopoeia, 10 tablets are assayed individually. eOut of this, 9 tablets should not contain less than 85% or more than 115% of the labelled drug content. 10 tablet should not contain less than 75% or more than 125% of the labelled drug content.ACTIVE PHARMACEUTICAL PERCENTAGE TEST ePercentage of medicament or active pharmaceutical ingredient, are calculated by taking sample of tablets and then assay is carried out. Result of the tablets should be within the prescribed percentage limit in pharmacopoeia.DISINTEGRATION TEST eGenerally, when a drug is taken, it should be readily : "available to the body. °First important step of a tablet to be readily available :+ breakdown of the tablet into smaller particles or granules — process is called Disintegration. eTime taken for a tablet to disintegrate is measured in a device described in the USP. «Disintegration is mainly used as a guide for the formulator in preparing an optimum tablet formulation.APPARATUS — DISINTEGRATION APPARATUS eThe USP device for disintegration comprises — 6 glass tubes that are 3 inches long, open at the top, and closed at the bottom with a 10 mesh screen in the basket rack assembly, °One tablet is placed in each tube and a perforated plastic dise is placed over the tablet. ¢The basket rack is positioned in a Llitre beaker of water or simulated gastric fluid or intestinal fluid, at 37°C. eThe assembly moves up and down at a specified rate using the help of a standard motor driven device. °Time taken to disintegrate the tablets, and all particles must pass through the 10 mesh screen in the standard time.*Uncoated tablets :- water is used a disintegration medium, and all 6 tablets should disintegrate within 15 minutes. eSugar Coated tablets :- all tablets should disintegrate within 1 hour. If a tablet does not pass the test, the disintegration medium is changed from water to 0.1M HCl, and the test is repeated. Failure in this, will lead to rejection of the whole batch. eFilm coated tablets :- tablets should disintegrate in 30 minutes, *Enteric coated tablets :- test is carried out for 2 hours first in 0.1 M HCl, and the tablets should not disintegrate. Then the tablets are tested with a simulated intestinal fluid for the next hour.DISSOLUTION TEST Dissolution test is carried out to :- Show that the drug is released up to 100%. eShow that the drug release is uniform batch to batch, There are different types of dissolution apparatus according to the United States Pharmacopoeia.eln general, dissolution apparatus consists of a cylindrical flask with a hemispherical bottom, made of glass or transparent plastic having 1000ml volume capacity. eFlask is partially immersed in a temperature bath maintained at 37°C. «Flask is fitted with a cover having 4 holes — one hole for the shaft with a basket or paddle, second for thermometer, and other holes for sampling. eOther end of the shaft is attached to variable speed driven motor that rotates at 25-150 rpm. Dissolution test is first conducted with 6 tablets, if a failure occurs the test is repeated with 6 tablets. On failure again, the test is repeated with 12 tablets.APPARATUS | — ROTATING BASKET TYPE °A cylindrical basket is placed at the end of the shaft, constructing with a non reactive mesh. Tablet is placed in the basket, and the pores in the mesh allow the dissolving drug to move from the basket to the holding flask. *Start motor and seed is adjusted to 100 rom. eAt a specified time interval, sample is withdrawn and the same volume of dissolution medium is replaced. eSamples are tested by UV spectroscopy, or chromatography.Basket Shaft Sampling Point Vessel BasketAPPARATUS II —- PADDLE TYPE *Rotating shaft is fixed to a blade attached vertically at the end. eThe blade is meant to act as a stirrer to ix the drug being tested with the liquid. *Drug is placed in the flask. eStart motor and seed is adjusted to 100 rom. «At a specified time interval, sample is withdrawn and the same volume of dissolution medium is replaced. eSamples are tested by UV spectroscopy, or chromatography.PERCENTAGE OF WEIGHT GAIN IN COATED TABLETS «Difference in weight of the final product and the initial uncoated tablet is calculated and the percentage is noted and checked according to the standard values in the pharmacopoeia.THICKNESS OF FILM IN COATED TABLETS Difference in the thickness of the coated tablet and uncoated tablet is measured using a micrometer or sliding caliper scale. eNote the value is noted and checked according to the standard values in the pharmacopoeia.