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Tablets - Tablets - ll

By fagosonBy fagoson Department of Department of

PharmacyPharmacy NUBNUB

Pharmaceutical Technology

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““A tablet is a solid single unit dosage form A tablet is a solid single unit dosage form containing one or more active ingredients with containing one or more active ingredients with or without auxillary substances, prepared by or without auxillary substances, prepared by compression and molding.”compression and molding.”

Intended Intended mainlymainly for oral administration for oral administration

Most commonly are disk shaped with convex surfacesMost commonly are disk shaped with convex surfaces

Available in special shape like round, oval, oblong, Available in special shape like round, oval, oblong, cylindrical, square, triangularcylindrical, square, triangular

Widely used solid dosage form because they offer a Widely used solid dosage form because they offer a number of advantages to the patient, prescriber, number of advantages to the patient, prescriber, manufacturer and manufacturing pharmacistmanufacturer and manufacturing pharmacist

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Essential qualities of a good TabletsEssential qualities of a good Tablets

--They should be accurate and uniform in weightThey should be accurate and uniform in weight--The drugs should be uniformly distributed The drugs should be uniformly distributed

throughout the tabletsthroughout the tablets-The size and shape should be reasonable for -The size and shape should be reasonable for

easy administrationeasy administration--The tablets should not be too hard that it may The tablets should not be too hard that it may

not disintegrate in the Stomachnot disintegrate in the Stomach-There should not be any incompatibilities-There should not be any incompatibilities--They should be chemically and physically They should be chemically and physically

stable during storage . Cont. stable during storage . Cont.

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Essential qualities of a good TabletsEssential qualities of a good Tablets

- They should not break during transportation - They should not break during transportation or crumble in the hands of the patientor crumble in the hands of the patient

- They should be attractive in appearances- They should be attractive in appearances- There should not be any manufacturing- There should not be any manufacturing defects like cracking, chipping discolourationdefects like cracking, chipping discolouration- - After disintegration it should release the After disintegration it should release the

drug readilydrug readily- They should be easy and economical in - They should be easy and economical in

productionproduction..

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AdvantagesAdvantages - Offer greatest dose precision and the least content - Offer greatest dose precision and the least content

variabilityvariability

- - easy to be swallowed or administeredeasy to be swallowed or administered

- easy to handle and carry by the patient- easy to handle and carry by the patient

- economical, manufacturing cost are low, manufacturing - economical, manufacturing cost are low, manufacturing speed is quite highspeed is quite high

- most stable with respect to physical, chemical and - most stable with respect to physical, chemical and microbiological attributes microbiological attributes

- - Bitter, unpleasant taste and nauseous odour of Bitter, unpleasant taste and nauseous odour of medicaments can be easily masked by administering in the medicaments can be easily masked by administering in the form of coated tabletform of coated tablet

--

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Advantage (Continued)Advantage (Continued)

- product identification is probably the easiest - product identification is probably the easiest because of the variety of shapes and colours of because of the variety of shapes and colours of tablets that are possibletablets that are possible

- the lightest and the more compact of all dosage - the lightest and the more compact of all dosage formsforms

- the easiest and the cheapest to pack and transport- the easiest and the cheapest to pack and transport

- don’t require any measurement of dose- don’t require any measurement of dose

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Advantage (continued)Advantage (continued)

Can be divided into halves, quarters by drawing Can be divided into halves, quarters by drawing lines during manufacture to facilitate breakage lines during manufacture to facilitate breakage whenever a fractional dose is requiredwhenever a fractional dose is required

Lend themselves to certain special release profile Lend themselves to certain special release profile such as enteric or delayed release productssuch as enteric or delayed release products

Attractive and elegant in appearanceAttractive and elegant in appearance

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In Summary Solid Dosage Forms, Most Notably Tablets Provide Advantages

To the pharmacist

in storage, dispensing, and control

convenience of use

To the patient

To the physician cheaper due to mass production and easier to manufacture, simplicity, economy, stability, and

convenienceTo the manufacturer

of product identification, dosage accuracy and precision, improved control and more reliable therapy

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DisadvantagesDisadvantages

AmorphousAmorphous and Low density drugs are difficult to and Low density drugs are difficult to compress.compress.

High dosesHigh doses are difficult to formulate as tablet dosage are difficult to formulate as tablet dosage form.form.

Bitter Bitter tastingtasting and objectionable and objectionable odouodour drugs require r drugs require special treatment like coating or encapsulation and special treatment like coating or encapsulation and increase the cost. increase the cost. Drugs that are sensitive to Drugs that are sensitive to oxygenoxygen or atmospheric or atmospheric moisture may also require special coating as well as costly moisture may also require special coating as well as costly packaging which may increase the overall cost of finished packaging which may increase the overall cost of finished productproduct

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Disadvantage (Continued)Disadvantage (Continued)

Drugs with poor Drugs with poor wettingwetting and slow dissolution properties and slow dissolution properties are difficult to convert into tablets which will provide full are difficult to convert into tablets which will provide full drug bioavailability.drug bioavailability.

Drugs that are Drugs that are liquidliquid at room temperature can not be at room temperature can not be formulated in tablet dosage formformulated in tablet dosage form

A major disadvantage with respect to convenience of A major disadvantage with respect to convenience of patients is the difficulty of patients is the difficulty of swallowingswallowing specially by specially by children children and ill patientsand ill patients

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Different Different TypesTypes of Tablets of Tablets

Classified into a number of categories, based on Classified into a number of categories, based on theirtheir-Their methods of manufacture-Their methods of manufacture-Type of drug delivery system-Type of drug delivery system- Formulation and Functions- Formulation and Functions

**Not all classes are entirely different but mostly **Not all classes are entirely different but mostly overlap each other, such as,overlap each other, such as,

- Chewable and Effervescent tablets are single - Chewable and Effervescent tablets are single layered uncoated tabletslayered uncoated tablets

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Classification (continued)Classification (continued)

Table1. Classified based on the method of manufacture andTable1. Classified based on the method of manufacture andtype of drug deliver systemtype of drug deliver system

(A) Tablets ingested orally: (A) Tablets ingested orally:

-- Compressed tablet, e.g. Paracetamol tablet

– Multiple compressed tablet

– Delayed release tablet, e.g. Enteric coated Bisacodyl tablet

– Sugar coated tablet, e.g. Multivitamin tablet

– Film coated tablet, e.g. Metronidazole tablet

– Chewable tablet, e.g. Antacid

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Classification (continued)Classification (continued)

(B) Tablets used in oral cavity : (B) Tablets used in oral cavity :

– Buccal tablet, e.g. Vitamin-c tablet

– Sublingual tablet, e.g. Vicks Menthol tablet

– Troches or lozenges

– Dental cone

(C) Tablets administered by other routes: (C) Tablets administered by other routes:

- Implantation tablet - Suppositories or Inserts, e.g. Clotrimazole tablet

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(D) Tablets used to prepare solution:(D) Tablets used to prepare solution: – Effervescent tablet, e.g. Dispirin tablet (Aspirin)

– Dispensing tablet, e.g. Enzyme tablet (Digiplex)

– Hypodermic tablet

– Tablet triturates e.g. Enzyme tablet (Digiplex)

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Standard compressed tabletStandard compressed tablet- - Prepared by single compression Prepared by single compression

- employ any of the three basic methods of manufactures: - employ any of the three basic methods of manufactures: wet wet granulation, dry granulation and direct compression.granulation, dry granulation and direct compression.

- most of the tablets containing drugs intended to exert a local - most of the tablets containing drugs intended to exert a local effect in the GIT are of this type (antacids and adsorbents)effect in the GIT are of this type (antacids and adsorbents)

- - Other drugs in this group are intended to produce systemic Other drugs in this group are intended to produce systemic effect.effect.

- - Tablets break up and particle deaggregation are importantTablets break up and particle deaggregation are important

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Multiple compressed TabletMultiple compressed TabletTablets of this category are usually prepared for one of Tablets of this category are usually prepared for one of

the two reasons:-the two reasons:-a. to separate physically or chemically incompatible a. to separate physically or chemically incompatible

ingredientsingredientsb. to produce repeat action or prolonged action productsb. to produce repeat action or prolonged action products - - layered tablets consist of parallel layers obtained bylayered tablets consist of parallel layers obtained bysuccessive compression of particles of different comp.successive compression of particles of different comp.

- press coated or dry coated tablets are prepared- press coated or dry coated tablets are prepared by compressing a layer of granules over a previouslyby compressing a layer of granules over a previouslycompressed tablets. (manesty drycota).compressed tablets. (manesty drycota).

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The layered tablets are rapid, surface contact between The layered tablets are rapid, surface contact between layers is lessened, production is simpler so preferred.layers is lessened, production is simpler so preferred.The shortcomings of this category of dosage form for The shortcomings of this category of dosage form for repeat – action products is that its performance is repeat – action products is that its performance is highly dependant on gastric empting.highly dependant on gastric empting.

XX, XX, If the second layer or core tablet quickly leaves the If the second layer or core tablet quickly leaves the stomach following release of the initial fast release stomach following release of the initial fast release dose, an entirely different blood level profile results dose, an entirely different blood level profile results than if there is a several hour or longer delay before than if there is a several hour or longer delay before the second fraction is emptied.the second fraction is emptied.

- this is the reason that relatively few repeat –action or - this is the reason that relatively few repeat –action or controlled release products using this approach are controlled release products using this approach are marketed. marketed.

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Repeat action tabletsRepeat action tablets

In addition to compressed tablets, sugar coated tablet In addition to compressed tablets, sugar coated tablet may also employed.may also employed.

The core tablet is usually coated with shellac or an The core tablet is usually coated with shellac or an enteric polymer so that it will not release the loading enteric polymer so that it will not release the loading drug in the stomach.drug in the stomach.

The second dose of drug is then added in the sugar The second dose of drug is then added in the sugar coating.coating.

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Delayed action and enteric coated tabletDelayed action and enteric coated tablet

The delay action tablet dosage form is intended to The delay action tablet dosage form is intended to release a drug after some time delay or after the release a drug after some time delay or after the tablet has passed through the part of GI tract into tablet has passed through the part of GI tract into another.another.The enteric coated tablet is the most common The enteric coated tablet is the most common exampleexampleAll enteric coated tablets are a type of delayed All enteric coated tablets are a type of delayed action tablet but not all delayed action tablet are action tablet but not all delayed action tablet are entericenteric Cellulose acetate phthalate, Polyvinyl acetate Cellulose acetate phthalate, Polyvinyl acetate phthalate, Hydroxypropyl methyl cellulose phthate phthalate, Hydroxypropyl methyl cellulose phthate have come into use for thishave come into use for this . .These polymers being acid esters, are insoluble in These polymers being acid esters, are insoluble in gastric media that have a pH up to about 4.gastric media that have a pH up to about 4.

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Chewable tabletsChewable tabletsAre compressed tablets which have a smooth, rapid disintegration when chewed or allowed to dissolve in the mouth and contains a creamy base of a specially flavored and colored mannitol.Two major advantages are,Two major advantages are,

a.The dose of most antacid is large so that the typical a.The dose of most antacid is large so that the typical antacid tablet would be too large to swallowantacid tablet would be too large to swallow

b.The activity of antacid is related to its particle size. If b.The activity of antacid is related to its particle size. If the tablet is chewed prior to swallowing better acid the tablet is chewed prior to swallowing better acid neutralizing may be possible from a given antacid neutralizing may be possible from a given antacid dose dose

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Xylitol may be used in the preparation of sugar-free chewable tablets. Xylitol is sweeter than mannitol.lubricant and binders must not affect the texture or desired hardness of the tabletcolorant and tart or fruity flavorants are commonly employed to enhance the appeal of the tablets Examples of chewable tablets: Calcium carbonate - antacids; Erythromycin - antibiotics; Didanosine - anti-infectives; Carbamazepine - anticonvulsants; Isosorbide dinitrate - vasodilator; Acetaminophen - analgesics; various vitamins and cold-allergy combination tablet

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Tablets used in the oral cavityTablets used in the oral cavityThis type of tablet are placed in the mouth but not This type of tablet are placed in the mouth but not swallowed.swallowed.

*Buccal and sublingual tablets*Buccal and sublingual tablets

These tablets , though not swallowed, are intended to These tablets , though not swallowed, are intended to provide systemic drug action.provide systemic drug action.

These are small, flat, usually oval dosage forms to be These are small, flat, usually oval dosage forms to be inserted in the buccal , or cheek, pouch (buccal tablet) or inserted in the buccal , or cheek, pouch (buccal tablet) or beneath the tongue (sublingual tablets).beneath the tongue (sublingual tablets).

The drug is absorbed directly through the oral mucosa, The drug is absorbed directly through the oral mucosa, thereby avoiding the acid and enzymatic environment of thereby avoiding the acid and enzymatic environment of the stomach and the drug metabolizing enzymes of the the stomach and the drug metabolizing enzymes of the liver. liver.

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Drugs are commonly administered by the oral Drugs are commonly administered by the oral mucosal routemucosal route::

the vasodilator glyceryl trinitratethe vasodilator glyceryl trinitrate: : Steroids, such as Steroids, such as methyl testosteronemethyl testosterone, , testosterone propionatetestosterone propionate, , estradioestradiol: and, possibly, some miscellaneous l: and, possibly, some miscellaneous hormones and drugshormones and drugs, such as , such as pancreatic pancreatic lipotropic hormone factors,lipotropic hormone factors, hesperidinhesperidin, and , and nicotinic acid.nicotinic acid.

Drugs that may be absorbed via the oral Drugs that may be absorbed via the oral mucosa have several possible advantagesmucosa have several possible advantages: : (1) Avoidance of the gastric environment and the (1) Avoidance of the gastric environment and the decomposition it may produce with some steroids and decomposition it may produce with some steroids and hormone (2) a more rapid onset of drug action than hormone (2) a more rapid onset of drug action than occurs with tablets which are swallowed (3) Reduction of occurs with tablets which are swallowed (3) Reduction of nausea, with drugs that produce this effect when nausea, with drugs that produce this effect when swallowed (4) More efficient drug utilization (lower dose), swallowed (4) More efficient drug utilization (lower dose), owing to avoidance of inactivation by liver drug owing to avoidance of inactivation by liver drug metabolising enzymes.metabolising enzymes.

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. Drugs absorbed from the gastrointestinal tract enter the mesenteric circulation . Drugs absorbed from the gastrointestinal tract enter the mesenteric circulation which feeds directly into the liver via the portal vein. Drug absorption from the which feeds directly into the liver via the portal vein. Drug absorption from the oral cavity involves drug diffusion into the blood and lymph canals through the oral cavity involves drug diffusion into the blood and lymph canals through the sublingual or oral mucosa. Blood is supplied to this region via the external sublingual or oral mucosa. Blood is supplied to this region via the external carotid artery and is returned via the jugular veins into the general circulation carotid artery and is returned via the jugular veins into the general circulation rather than going directly to the portal vein. Many steroids are either relatively or rather than going directly to the portal vein. Many steroids are either relatively or totally inert if ingested owing to inactivation by liver enzymes. This loss of totally inert if ingested owing to inactivation by liver enzymes. This loss of potency can be circumvented by other modes of administration such as potency can be circumvented by other modes of administration such as intramuscular injection, implantation of tablets, use of vaginal suppositories, or intramuscular injection, implantation of tablets, use of vaginal suppositories, or absorption through the oral mucosa. The latter method, in many instances, is absorption through the oral mucosa. The latter method, in many instances, is preferable.preferable.Since most drugs, including weakly acidic drug moieties, are probably absorbed Since most drugs, including weakly acidic drug moieties, are probably absorbed primarily in the upper small intestine. The tablet must disintegrate, the drug primarily in the upper small intestine. The tablet must disintegrate, the drug dissolve, and the stomach empty at least partially before drug absorption begin. dissolve, and the stomach empty at least partially before drug absorption begin. Therefore , a time lag of 30 minutes or more (corresponding to the time required Therefore , a time lag of 30 minutes or more (corresponding to the time required for the drug to be dissolved and leave the stomach) is typical before a drug effect for the drug to be dissolved and leave the stomach) is typical before a drug effect is exerted after swallowing a tablet. on the other hand , total drug absorption is exerted after swallowing a tablet. on the other hand , total drug absorption typically occurs within 30 minutes after buccal or sublingual tablets have been typically occurs within 30 minutes after buccal or sublingual tablets have been administered and onset of action is common with vasodilator drugs..administered and onset of action is common with vasodilator drugs..Buccal and sublingual tablets are designed not to disintegrate but to dissolve Buccal and sublingual tablets are designed not to disintegrate but to dissolve slowly over a 15 to 30 minute period. The tablet composition should not promote slowly over a 15 to 30 minute period. The tablet composition should not promote salivation, which would result in swallowing dissolved drug, thereby salivation, which would result in swallowing dissolved drug, thereby circumventing the purpose of the buccal or sublingual tablets.circumventing the purpose of the buccal or sublingual tablets.

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Dental conesDental cones

The cones may contain an antibiotic or The cones may contain an antibiotic or antiseptic typically in a filler of Sodium antiseptic typically in a filler of Sodium bicarbonate, sodium chloride, amino acid, bicarbonate, sodium chloride, amino acid, or lactose. or lactose.

The cones are formulated and compression The cones are formulated and compression so that a small volume of serum or fluid will so that a small volume of serum or fluid will cause disintegration and dissolution in 20 to cause disintegration and dissolution in 20 to 30 minutes.30 minutes.

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Tablets administered by other routesTablets administered by other routes

Implantation tabletsImplantation tablets

This is also known as pellets, are small sterile tablets, This is also known as pellets, are small sterile tablets, cylindrical shaped and usually not over 8 mm. in length, for cylindrical shaped and usually not over 8 mm. in length, for subcutaneous implantation in man or animals to provide subcutaneous implantation in man or animals to provide very prolonged drug effects – for 3 to 6 months or longer.very prolonged drug effects – for 3 to 6 months or longer.

In man, use of this dosage form is limited to very potent In man, use of this dosage form is limited to very potent drugs which are not orally absorbed, notably steroids such drugs which are not orally absorbed, notably steroids such as Desoxycorticosterone, testosterone, or estradiol.as Desoxycorticosterone, testosterone, or estradiol.

The major advantage of the dosage form is to provide The major advantage of the dosage form is to provide continuous therapy over many months without the need continuous therapy over many months without the need for repeated parenteral dosing. Over a long periods of time for repeated parenteral dosing. Over a long periods of time this form of therapy can be most economical. Also, it may this form of therapy can be most economical. Also, it may provide the most even and uniform hormone therapy.provide the most even and uniform hormone therapy.

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Implantation tabletsImplantation tablets

The immediate and potential disadvantage ofThe immediate and potential disadvantage ofimplantation therapy are:implantation therapy are:

- the surgical technique which may be required - the surgical technique which may be required for implantation for implantation - the difficulty of maintaining a constant drug - the difficulty of maintaining a constant drug release rate as the pellet changes geometry with release rate as the pellet changes geometry with dissolutiondissolution

- the possibility of a histopathological (tissue - the possibility of a histopathological (tissue toxicity) reaction against the implanted ‘foreign toxicity) reaction against the implanted ‘foreign body’body’

-the need to employ a surgical technique to -the need to employ a surgical technique to terminate the therapy should such termination terminate the therapy should such termination become necessarybecome necessary

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Vaginal tabletsVaginal tablets

Also called inserts, are generally ovoid or Also called inserts, are generally ovoid or pear shaped made by compression and pear shaped made by compression and intended to undergo dissolution and drug intended to undergo dissolution and drug release in the vaginal cavity.release in the vaginal cavity.The tablets are usually used in the treatment The tablets are usually used in the treatment of trichomonas vaginitis and of trichomonas vaginitis and contain organic iodine (iodochlor or contain organic iodine (iodochlor or iodohydroxyquinoline compounds) or other iodohydroxyquinoline compounds) or other antiseptics, astringents, or steroids in a antiseptics, astringents, or steroids in a soluble base of lactose or sodium soluble base of lactose or sodium biocarbonate.biocarbonate.

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Effervescent tabletsEffervescent tablets

These tablet produce effervescence when These tablet produce effervescence when added to cold water. Effervescence which added to cold water. Effervescence which is usually carbon dioxide is generated due is usually carbon dioxide is generated due to chemical reaction which take place to chemical reaction which take place between a Bicarbonate and an acid (citric between a Bicarbonate and an acid (citric acid and Tataric acid)acid and Tataric acid)The effervescence causes rapid The effervescence causes rapid disintegration of the tablet and also disintegration of the tablet and also increases the palatability increases the palatability ।।