Tablets Report

7/29/2019 Tablets Report

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TabletsBy: Katryn Punsalang



Definition:

• Solid dosage form

• Contains medicinal substances

– With or without suitable diluents

• Compressed/ molded powders or granules

• Single doses intended for oral administration

• Has lines or break marks (scorings)

• Has symbols or other markings



• Usually taken for Systemic effect

– results after absorption from the various surfacesalong the gastrointestinal tract.

• Slower onset of action BUT greater duration of action

• Most natural

• Uncomplicated

• Convenient

• Safe means of administration



Classification of tablets

• Tablet can be classified according to their:A. Method of Manufacture

1. Compression

2. Molding

B. Intended use –. uncoated tablets;

–. coated tablets (including film-coated and sugar-coated tablets);

–. soluble tablets;

–. dispersible tablets;

–. effervescent tablets;

–. chewable tablets;

–. tablets for use in the mouth (including sublingual and buccal tablets);

–.

modified-release tablets (including delayed-release tablets (gastro- resistant/enteric-coated tablets) and sustained-release tablets (extended-/prolonged-release tablets)



Excipients used in Tablet Preparation

• Diluents or fillers

– add the necessary bulk to a formulation to preparetablets of the desired size.

• Binders or adhesives – promote adhesion of the particles of the formulation,

allowing a granulation to be prepared and maintainingthe integrity of the final tablet.

• Disintegrants or disintegrating agents – promote breakup of the tablets after administration

to smaller particles for ready drug availability.



• Antiadherents, glidants, lubricants, or lubri-cating agents

–

enhance the flow of the material into the tabletdies, minimize wear of the punches and dies,prevent fill material from sticking to the punchesand dies, and produce tablets with a sheen.

•

Miscellaneous adjuncts: – Colorants- add to the pharmaceutical elegance of

the product

– Flavorants- mask any unpleasant tastes

– Coatings- protect the active ingredient of the drugfrom any unwanted biological interaction before itreaches the intended site of action.



Manufacturing Methods

1. Compression

1. Wet granulation

2. Dry granulation (roll compaction orslugging)

3. Direct compression

2. Molding



Compressed Tablets

• Contains medicinal agent(s) andsuitable pharmaceutical excipients

•

Tablets for oral, buccal, sublingual, orvaginal administration may beprepared by compression.

• Most widely used dosage form (USP)



• PHYSICAL FEATURES:

– round, oblong, or unique in shape

– thick or thin

– large or small in diameter; flat or convex

– determined by the die and punches used in compression.

– The less concave the punches, the flatter the tablets; conversely

– the more concave the punches, the more convex the resulting tablets.

– unscored or scored in halves, thirds, or quadrants

– engraved or imprinted with an identifying symbol and/or code number

– coated or uncoated

– colored or uncolored

– one, two, or three layered.

Compressed Tablets



Quality Standards and CompendialRequirements

• Tablet weight

–Determined by the quantity of fill in the die of a tablet.

• Weight variation

–Weight variation test(USP), average weight of 10 tablets, weighed individually.

• Content uniformity

–10 dosage units are individually assayed for their content

–Act. Ing. In each dosage unit should be 85%-115%, deviation less than 6%

• Thickness

–Determined by the diameter of the die, compaction characteristics of the fill material, andthe force/pressure applied during compression

• Hardness

–Can affect disintegration and dissolution.

– Tablets are in general be sufficient enough to

–resist breaking during normal handling and

–soft enough to disintegrate after swallowing

–Pressure is a determinant: pressure= harder tablets: CONTROL PRESSURED is used

–Measured by hand gauze or automated equipment( Friabilator: tendency to crumble)

–Lozenges and buccal tabs= hard

– Immediate drug release tabs: soft



• Disintegration

– Tablet must first disintegrate before absorption

– Important for tablets that should be absorbed in the GI tract.

– Provides drug particles with an increased surface area – Must pass disintegration test via an in vitro

• Dissolution

– It guides formulation and product development toward productoptimization

– Manufacturing may be monitored as a component of the over allqlty assurance program

– Consistent in vitro dissolution testing ensures bioequivalence frombatch to batch

– It is a requirement for regulatory approval of marketing productsregistered with the FDA

GOAL is provide a reasonable prediction of the drug’s in vitrobioavailability.

Drug’s solubility (high or low) and it’s intestinal permeability (high

or low)



4 categories of Drug Dissolution

4 categories:

I. high solubility and permeability: dissolution rate isslower than gastric emptying rate(rate limiting)

II. low solubility and high permeability: dissolution may

be the rate limiting step for absorption

III. high solubility and low permeability: permeability isthe rate controlling step

IV. low solubility and low permeability: significant

problems are likely for oral drug delivery.



3 methods in Compressed Tablet Manufacturing

1.Wet granulation

2.Dry granulation

3.Direct compression



Wet granulation• Steps:

1. Weighing and blending the ingredients – Act. ing. + diluent/filler+ disintegrating agent= POWDER mixture

– Fillers: lactose, microcrystalline cellulose, starch, powdered sucrose, and calciumphosphate.

– Disintegrating Agents: croscarmellose, corn/ potato starches, sodium starch glycolate,sodium carboxymethylcellulose, polyvinylpyrrolidone (PVP), crospovidone, cation exchangeresins, alginic acid, and other materials that swell or expand on exposure to moisture and

effect the rupture or breakup of the tablet in the gastrointestinal tract.

2. Preparing the dampened powder or damp mass

– Powder mixture + liquid binder= damp powder/ mass

– Liquid binder: facilitate adhesion to powder particles

– povidone, an aqueous preparation of cornstarch (10% to 20%), glucose solution (25% to50%), molasses, methylcellulose (3%), carboxymethylcellulose, and microcrystallinecellulose

3. Screening the dampened powder or damp mass into pellets or granules

– Dampened powder granules: screened

– Wet mass: passed through a screen

– Resultant granules: spread evenly on large lined trays, dried to consistent weight orconstant moisture content



4. Drying the granules

– Thermostatically controlled ovens

– Constant recording of: time, temp., humidity

5. Sizing the granulation by Dry screening – Necessary so that die cavities for tablet compression may be

completely and rapidly be filled by the free- flowing granulation.

– Dried Granules: passed through screen of a smaller mesh

– Smaller the tablet to be produced: smaller granules

– 12-20 mesh size are used

– Air spaces of too large granules: production of uneven tablets



6. Adding lubricant and blending

– Dry lubricant is dusted over the spread outgranulation through a fine mesh screen.

– Lubricants: magnesium stearate, calciumstearate, stearic acid, talc, and sodium stearylfumarate

–

improve the flow of the granulation in thehopper die cavity.

– Prevent adhesion of the tablet formulation tothe punches and dies during compression.

– Reduce friction bet. Tablet and die wall duringthe ejection of the tablet from the machine.

– Give a sheen to the finished tablet

7. Forming tablets by compression





All in one Granulation Methods

A. Allow the entire process of granulation to be completed in acontinuous fluid bed process using the fluid bed granulator.

• STEPS:

1. Pre-blending the formulation powder (Act. Ing., fillers,disintegrants) in a bed with fluidized air

2. Granulating the mixture by spraying onto the fluidized powderbed, a liquid binder (aq. Soln. of acacia, hydroxypropyl cellulose,or povidone)

3. Drying the granulated product to the desired moisture content.

B. Microwave vacuum processing: wet mass is mixed, vacuumed,and microwaved(to reduce the drying time). Overall process onlytakes usually 90 mins.



DRY GRANULATION

• Powder mixture is compacted in large pieces

• Broken down or sized into granules

• Active Ing. Or the diluent must have cohesive properties

•

Applicable to materials that cannot be prepared via wetgranulation bec. They degrade in moisture or theelevated temps. Required for drying the granules.

A. SLUGGING

B. ROLLER COMPACTION



Dry Granulation

A.Slugging

1. Weigh and mixed the ingredients= Powder mixture

2. Powder mixture is slugged, or compressed into a large flattablets or pellets (1 inch in diameter)= slugs

3. Slugs are broken up by hand or by a mill

4. Passed through a screen of desired mesh

•. Lubricant is added in the usual manner and tablets areprepared by compression.

•. Ex. Aspirin (hydrolyzed on exposure to moisture)



Dry Granulation

B. Roller Compaction

• Powder compactors increase density of powder bypressing it bet. Rollers at 1-6 tons of pressure.

•

Compacted material: broken up, sized, lubricatedand prepared by compression.

• Preferred over slugging

• Binding agents used: methylcellulose or

hydroxymethylcellulose (6% to 12%)(produce goodtablet hardness and friability)





Tableting of Granulation•

Various types of tablet presses/ tableting machines• Similar in basic function and operation

• All compress a tablet formulation within a steel diecavity by the pressure exerted by the movement of

two steel punches: LOWER and UPPER punch – Single- punch tablet press

– Rotary tablet machines

– Single rotary press (16 sets of punches and dies)

–

Double rotary press (27,33,37,41,49 sets of punches and dies, twotablets for each die)

– Induced die feeders (for high speed production, 10,000 or moretablets per min. of operation)

• Problems: Lamination (horizontal striations)

● : tablet capping (top of the tablet separates due to

insufficient time to bond after compression)





DIRECT COMPRESSION

• Free- flowing and cohesive properties allow the direct compression of some granular chemicals (eg. KCl)

• Pharmaceutical excipients maybe used for chemicals without theseproperties:

– Fillers: pray-dried lactose, microcrystals of alpha-monohydrate lactose,

sucrose–invert sugar–corn starch mixtures, microcrystalline cellulose,crystalline maltose, and dicalcium phosphate

– Disintegrating agents: direct compression starch, sodium carboxymethylstarch, cross-linked carboxymethylcellulose fibers, and cross-linkedpolyvinylpyrrolidone

– Lubricants: magnesium stearate and talc

– Glidants: fumed silicon dioxide

• Problems encountered: capping, splitting, laminating of tablets due toair entrapment during direct compression.

• Solution: use forced or induced feeders

• Tablet Dedusting- removal of traces of loose powder adheering to

tablets after compression.





Types of Compressed Tablets

• MULTIPLY COMPRESSED TABLETS

– a tablet within a tablet

– Multiple layer

– Inner layer- core

– Outer layer- shell

– Each layer has different colors

– Each layer may contain different active ingredients

• chemical or physical incompatibility, staged drug release, or uniqueappearance of the layered tablet.

– Prepared by:

– initial compaction of a portion of fill material in a diefollowed by additional fill material and compression to form

multiple layers.



Sedative hypnotic2 layers: layer 1 released immediately

which puts one to sleep

other layer prolongs action keeping youaslee



SUGAR COATED TABLETS• Coated with a colored or uncolored sugar layer

• Coating:

• ADVANTAGES:

– Water soluble

– Quickly dissolves after swallowing

– Protects the enclosed drug from the environment

– Provides barrier against objectionable taste or odor

– Enhances the appearance of the product

– Permits imprinting of identifying manufacturer’s info.

• DISADVANTAGES: – Time and expertise are required in process

– Increase in size, weight, and shipping costs

– May add up to 50% to the weight and bulkiness of the product

• Examples:

-



Tofranil-has sugar coating applied to it isosorbideHCL

Antidepressant



FILM COATED TABLETS

• Coated with a thin layer of polymer capableof of forming a skin-like film.

• Film:

– Colored

– Advantage over sugarcoatings: more durable,less bulky, less time consuming to apply

– Designed to rupture and expose the core tabletat the desired site of action in the GI tract.

– Examples:



Clarithromycin



GELATIN COATED TABLETS

• Recent innovation (Gelcap)

• Capsule shaped compressed tablet

• Allows coated product to be about one- third

smaller than a capsule filled with an equalamount of powder.

• Gelatin coating:

– Facilitates swallowing – More tamper evident

– Example: Extra Strength Tylenol PM Gelcaps





ENTERIC COATED TABLETS

• Have delayed release features

• Designed to pass unchanged through the stomachto the intestines(where the tablet disintegrates andallow absorption to occur)

• Enteric coating is used:

– when the product is destroyed by gastric acid

– The product is irritating to the gastric mucosa

– When bypass of the stomach enhances drug absorption – Example: Ecotrin Tablets and Caplets (Smith Kline

Beecham)



Dulcolax OTC-AI is bisacodyl

[tablet] irritant laxative'



BUCCAL AND SUBLINGUAL TABLETS

• Flat, oval tablets

• Buccal- dissolved in the buccal pouch

– Erode slowly

• Sublingual- dissolved beneath the tongue – Dissolve promptly

– Provide rapid drug effects

– Example: Nitroglycerin

• Enable oral absorption of drugs that are destroyedby the gastric juice and/or are poorly absorbed inthe GI tract



Testosterone Buccal tabletHormone for men

30mg buccal tablet,MFG: ACTIENT



Sublingual TabletIsosorbide30, 60 mg

Mfg: Parke Davis

treat:angina pectoris



LOZENGES or TROCHES

• Disc shaped

• Act. Ing. + flavoring subs. (hard

candy/ sugar base)• Intended to be slowly dissolved in

the oral cavity

• For local effects/ systemic absorption• Example: Mycelex Troches (Bayer)



Cepastat LozengeAntiseptic

PHENOL/Mentholfor sore throat

14.5 mg phenolMFG: GSK

CLOTRIMAZOLEMFG: paddock labs

I: antifungal, thrush,ORALPHARYNGEAL

CANDIDIAS10mg oral lozenge



CHEWABLE TABLETS• Smooth, rapid disintegration

• Chewed or allowed to dissolve in the mouth

• Creamy base( flavored and colored mannitol: 70% as sweet assugar, 50% of the weight of the tablet.)

• Sorbitol, lactose, dextrose, glucose, crystalline maltose can be

alternatives to mannitol.• Xylitol is used for sugar free chewable tablets

• Useful for administration to patients with difficulty inswallowing large tablets (children and adults)

• Antacids (CaCo3) Antibiotics (erythromycin) analgesics(acetaminophen) vitamins

• Prepared by wet granulation and compression using onlyminimal degrees of pressure to produce a soft tablet

• Doesn’t contain disintegrant

• Examples: Pepcid Chewable Tablets (J&J Merck)



Mylanta chewable tablets(swallowed whole)



EFFERVESCENT TABLETS

• Prepared by compressing granulareffervescent salts that release gas when incontact with water.

•

Contains Act. Ing. That dissolves rapidly whenadded to water

• Bubble action: assist in breaking up the tabletand enhancing the dissolution of the active

drug• Examples: Alka-seltzer Original, Zantac

EFFERdose (GlaxoSmithKline)



Effer-K Potassium Chloride Supplement

Effervescent Tablets



MOLDING• Other way of preparing tablets

• Commercial preparation of tablets by molding has been replaced bytablet compression.

• Intended for tablets to dissolve rapidly in the mouth

• Do not contain disintegrants, lubricants, coatings.

• Prepared on a small laboratory scale

– Mold: hard rubber, hard plastic, metal

– Two parts: upper part (flat plate: DIE) and lower part (squat, flat: PUNCHES)

– BASE: Fine powders+ powdered lactose(w/ or w/o powdered sucrose for lessenbrittleness of tablet)

– A. Mix the dry ingredients via geometric dilution

– B. powder mixture is wetted with 50% mixture of water(binds the powdermixture upon drying) and alcohol( hastens drying)

– C. Fill the die with the material completely

– D. Fit the die in the punch and press the die down

– E. punches gently lift the fill material from the holes to rest upon the punchesfor drying



MOLDED TABLETS

• Prepared by molding rather than bycompression

• Resultant tablets are very soft andsoluble

• Designed for rapid dissolution



TABLET TRITURATES

• Small

• Usually cylindrical

• Contains small amounts of usually potent drugs

• Must be readily and completely soluble in water

• Only a few tablet triturate products are availablecommercially(ex. Nitroglycerin)

– Most of these are already prepared by compression

• minimum amount of pressure is applied in manufacturing

•

Combination of Sucrose and lactose are used as diluents• Used by pharmacists in compounding

– Triturates are inserted into capsules or dissolved in liquid to provideaccurate amts. Of potent drug subs.



HYPODERMIC TABLETS

• No longer available

• Originally used by physicians in extemporaneous prep.Of parenteral solns.

– Convenience to the physicians since they could easily carry

them in their bags and meet the needs of indv. Patients.

• Required number of tablets are dissolved in a suitablevehicle, sterility attained, and the injection performed.

– Issues on Sterility and availability of prefabricated injectable

products have eliminated their use.





DISPENSING TABLETS

• No longer used

• “Compounding tablets”

– Rxist’s used them to compound Rx.

• they were not dispensed much to patients

• Tablets contained large amts. Of highly potentdrug subs.

– Rxist’s could rapidly obtain premeasured amts. Of

compounding multiple dosage units.

• Had a dangerous potential of being inadvertentlydispensed



IMMEDIATE RELEASE TABLETS

• Designed to disintegrate and releasetheir medication with no special ratecontrolling features (ex. coatings).

● CATAFLAM (DICLOFENACPOTASSIUM)(NSAID)



INSTANTLY DISINTEGRATING/ DISSOLVING TABLETS

• Instant release tablets/ rapid dissolving tablets (RTDs)

• Disintegrating/ dissolving in the mouth within 15-30 seconds

• Designed for patients with difficulty in swallowing (children and adults)

• Liquefy on tongue. Patients swallow the liquid

• Prepared using very water soluble excipients designed to wick water into

the tablet for rapid disintegration/dissolution

• Techniques used in preparation:

– Lyophilization (ex. Zydis, R.P. Scherer)

– Soft direct compression (ex. Wow-Tab, Yamanouchi- Shaklee Pharma)

– Other methods (ex. Quicksolv, Janssen)

• Original fast dissolving tablets were molded for SUBLINGUAL use. (act. Ing.+ alcohol-water mixt.= paste)

• Have been used for drugs that are destroyed in the GI tract (ex. Testosterone; sublingually)




• More convenient to carry and administer (comp. tooral liquids)

• Packaged in cards or bubble type packaging

– Each individual tablets on its own cavity

• Disadvantages:

– Drug loading

– Taste masking

– Friability – Manufacturing costs

– Stability of the product






• Lyophilized Foam

– First entry in the RDT field was the Zydis delivery system

– Fastest disintegrating system on the market

– Dissolves in tongue in few seconds

– Prepared by:

– Mixture of gelatin, act. Ing., other components, pouring foam into the mold(servesas a unit dose dispensing pck.)

– The foam is lyophilized and the tablets in the mold are packaged

– Disadvantages:

– Masking of taste can be a problem

– Difficulty in removing from the package

– Claritin (loratidine) rapidly disintegrating tablets (Reditabs, ScheringCorporation): disintegrates within seconds after being placed on tongue,w/ or w/o water.




• Compression

– standard tableting technology with a composition that will enhancefluid uptake and tablet disintegration and dissolution

– Ex. Super-disintegrants incorporated with a small quantity of effervescent materialwill lead to intermediately fast disintegration.

– compressed a little thinner than standard tablets to allow for a largersurface area exposed to the saliva in the mouth

– Steps:

– placement in the mouth

– the disintegrant starts wicking water into the tablet.

– The effervescent materials start dissolving and aid in the breakup. – This continues until the tablet has disintegrated.

Ex. Dimetapp ND Orally Disintegrating Tablet (Nondrowsy Allergy Tablets).



EXTENDED-RELEASE TABLETS

• Controlled release tablets

• designed to release their medicationin a predetermined manner over anextended period.

• Ex. Simvastatin Niacin Extended

Release Tabs.



VAGINAL TABLETS

• Vaginal inserts

• uncoated, bullet-shaped or ovoid tablets

• inserted into the vagina for local effects

• prepared by compression

• shaped to fit snugly on plastic inserter devices thataccompany the product.

• They contain:

– anti-bacterials for the treatment of nonspecific vaginitis caused by

Haemophilus vaginalis – antifungals for the treatment of vulvovaginitis candidiasis caused

by Candida albicans and related species.

Ex.



Vagifemvaginal tablet

10mcgtreats atropic vaginitis



TABLET COATING

• protect the medicinal agent against destructiveexposure to air and/or humidity

• to mask the taste of the drug

•

to provide special characteristics of drug release(e.g., enteric coatings)

• to provide aesthetics or distinction to the product.

• to prevent inadvertent contact with the drug

substance and the effects of drug absorption – Ex. Proscar tablets (finasteride, Merck)

• SUGARCOATING TABLETS



• SUGARCOATING TABLETS

(a)waterproofing and sealing if needed

–

one or more coats of a waterproofing substance(eg.) pharmaceutical shellac or a polymer

(b) Subcoating

– three to five subcoats of a sugar-based syrup are

applied.

– This bonds the sugar coating to the tablet and providesrounding

(c) smoothing and final rounding

– 5 to 10 additional coatings of a thick syrup areapplied to complete the rounding and smooththe coatings

(d) finishing and coloring if desired



(d) finishing and coloring if desired

– several coats of a thin syrup containing thedesired colorant are applied

– attain final smoothness and the appropriate color to thetablets

(e) Imprinting and Polishing

–

passed through a special imprinting machine toimpart identification codes and other distinctivesymbols.

– Debossed, embossed, engraved

–

Special drum-shaped pans or ordinary coatingpans lined with canvas or other cloth withcarnauba wax and/or beeswax can be used forpolishing while tumbling on a pan



TABLET COATING

• Film coating

– Non aqueous or aqueous solutions

– Contents of Non Aq.:

– Film former

– Alloying substance

– Plasticizer

– Surfactant

– Opaquants and colorants

– Sweeteners, flavors, aromas

– Glossant

– Volatile oil

– Contents of Aq.:

– Film-forming polymer (7% to 18%)

– Plasticizer (0.5% to 2.0%)

– Colorant and opacifier (2.5% to 8%)

– Vehicle



TABLET COATING

• Enteric coating

– intended to pass through the stomach intact to disintegrate andrelease their drug content for absorption along the intestines

• design is based on the transit time required for passage tothe intestines

– may be accomplished through coatings of sufficient thickness

• Based on pH

• pharmaceutical shellac, hydroxypropyl methylcellulosephthalate, polyvinyl acetate phthalate, diethyl phthalate,

and cellulose acetate phthalate.



TABLET COATING

• FLUID BED OR AIR SUSPENSION COATING

-spray coating held in suspension by a column of air

– Bottom- spray method (WURSTER process)

– Top- spray method

– Tangential- spray technique

• COMPRESSION COATING

– core tablets (multiple layered tablets) may be sugarcoated bycompression

– coating material: form of a granulation or powder – more uniform and uses less coating material

– Tablets are lighter, smaller, and easier to swallow and less expensive topackage and ship.



IMPACT OF MANUFACTURING CHANGES ON SOLIDDOSAGE FORMS

• Alteration in quality and performancedue to changes in:

• FORMULATION

– (a) the use of starting raw materials

– (b) the use of different pharmaceuticalexcipients

– (c) the use of different quantities of thesame excipients in a formulation

– (d) the addition of a new excipient to a

formulation



• METHOD OF MANUFACTURING

– use of processing or manufacturing equipment of adifferent design

– a change in the steps or order in the process or

method

– different in-process controls, quality tests, or assaymethods

– production of different batch sizes

– employment of different product repro- cessingprocedures

– employment of a different manufacturing site.

IMPACT OF MANUFACTURING CHANGES ON SOLIDDOSAGE FORMS



PACKAGING AND STORING TABLETS

• Tablets are stored in tight containers

• in places of low humidity

• protected from extremes in temperature.

• desiccant packet- against decompositioncaused by moisture.

• light-resistant containers- for drugs that are

adversely affected by light• properly stored tablets will remain stable for

several years or more.

Documents

Tablets Report