*~ Tablets ~*

TABLETS solid pharmaceutical dosage form containing drug substance with or without suitable diluents

their shapes and dimensions are determined by use of various shaped punches and dies tablets are prepared primarily by compression, with limited number prepared by molding vary in size, shape, weight, hardness, thickness,disintegration depending upon use & method of manufacturing some tablets are scored, or grooved, which allows them to be easily broken into 2 or more parts

for oral tablets colorants, flavorants and coating of various type

for oral, buccal, sublingual, or vaginal administration may be prepared by compression and have different adjuncts layered tablets are prepared by initial compaction of a portion of fill material in a die followed by additional fill material and compression to form 2 or 3 layered tablets tablets that are not scored are not intended to be broken or cut

Accurate dosage since each tablet represent one dosage units Preference of anufacturers due to rapid ass production

Lease expensi e of the solid dosage for s and as to lightest in eight and therefore cheapest to pac . Easy to carry (capsules ay co e open)

Co pact and easy for the phar acist to store Che ically stable Can pro ide control of drug release

In Summary Solid Dosage Forms, Most Notably Tablets Provide Advantages

in storage, dispensing, and controlTo the pharmacist

convenience of use

To the patient

of product identification, dosage accuracy and precision, improved control and more reliable therapyTo the physician

cheaper due to mass production and easier to manufacture, simplicity, economy, stability, and convenienceTo the manufacturer

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COMPRESSED MULTIPLE COMPRESSED SUGAR - COATED CHOCOLATE - COLORED FILM COATED MOLDED ENTERIC COATED BUCCAL / SUBLINGUAL

EXTENDED RELEASE INSTANTLY DISINTEGRATING CHEWABLE VAGINAL TABLET TRITURATE HYPODERMIC TIMED-RELEASE(click)

PILLS

Examples oF Official Tablets

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Prepared by single compression, occur in various shapes and sizes and usually contain in addition to the medicinal substance/s a number of pharmaceutical adjuncts including: 1. Essential components - those that impart satisfactory characteristics to the formulation such as: a. Diluent or bulking agent - those substances that make up the major portion of the tablet b. Binders or granulators - those substances that glue powders together and cause them to form granules. They impart cohesive qualities to the powdered material. C. Disintegrants - material that help the tablet break up and dissolved to release the medicament for rapid dissolution

2. Compression Aids - those materials which impart satisfactory compression characteristics such as: a. Glidants - materials added to the formulation to enable the granules to flow from hopper on the tablet press to the die and for consistent and uniform fill. b. Lubricants - materials which aid in releasing the compressed tablet from the die c. Antiadhesives - materials needed to prevent the formation of residue films of tablets granulation in the punches

3. Supplementary Components - those that give additional desirable physical characteristics to the finished tablets a. Colors - materials added to a tablet for its aesthetic value, to provide a control during manufacture, and to distinguish one product from another. b. Flavors - materials added for the same reason above c. Sweetening Agents - those that are added to enhance the taste of the finished tablet especially when chewed.

Examples OF Diluents1. Lactose USP - It is the principal bulking agent used Advantages: 1. Inexpensive 2. Readily soluble 3. Stable and generally inert 2. Starches - wheat, corn, rice, potato - use as binders and disintegrants 3. Mannitol Advantages 1. Highly desirable for water-sensitive drugs 2. Appropriate for chewable tablets because of its taste 4. Sorbitol - use for direct tableting 5. Sucrose - serve as binder because of its cohesive property, and additional sweetness 4. Not softened by the friction forces of compression

Example Of Diluents 1. Starch Paste - aqueous solution of corn starch - 10 to 20% w/w 2. Aqueous Gelatin Solution - 10 to 20% w/w 3. Aqueous Glucose Solution - 25 to 50% w/w 4. Alcoholic Solution of ethylcellulose - 5% w/w

Examples Of Disintegrants 1. Starches - corn and potato 2. Clays - betonite and beegum 3. Cellulose - methylcellulose, sodium CMC 4. Algins - alginic acid and sodium alginate 5. Gums - locust bean, karaya, agar, tragacanth

A Well Made Compressed Tablets Possesses These Attributes 1. Ability to withstand the rigors of the mechanical treatment involved in the production, packaging, shipment and dispensing. 2. Freedom from defects such as cracks, chipped edges, discoloration, specking and contamination. 3. Reasonable chemical and physical stability during average storage conditions. 4. Ability to release the medicament in a reproducible and predictable manner.(click to return)

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Are prepared by subjecting to more than a single compression. The result maybe multiple layered tablet or tablet within tablet, the inner tablet being the core and the outer portion being the shell.

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Are compressed tablets which may be coated with colored or uncolored sugar. The coating is water-soluble and is quickly dissolved after swallowing

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Advantages: 1. It serves the varied purposes and protecting the drug from air and humidity. 2. Provides the taste or smell barrier to objectionable tasting or smelling drugs. 3. It enhances the appearance of many CT Disadvantages: 1. Time and expertise required by the process 2. Increase in size and weight of the CT which may be 50% larger and heavier than the original uncoated tablet.

Basic Steps In Sugar Coating Of Compressed Tablets and Granules 1. Sealing - This done to separate the core from the water that is used inthe coating process. Waterproofing materials - cellulose acetate, zein, shallac, and resins are adhesive in nature, therefore, dusting powders such as asbestos-free talc and terra alba are applied in between two seals coats up to six seal coats to prevent the tablets from sticking with one another and to the coating pan.

2. Subcoating

- this is to round off the tablet - to improve the bond between seal coat and the sugar coat, and to standardized tablet size.

Examples: solutions of gelatin and/or acacia

3. Syruping - It usually involves 3 basis phases such as grossing, heavysugar coating, and regular syrup coating.

3 BASIC PHASESa. Grossing - the application of a syrup solution with sub coatingpowder dispersed in it and with dye added to develop a color base for the final syrup application

b. Heavy sugar coating - application of a syrup concentrate to buildup a solid rapidly and attain a specific tablet volume.

C. Regular syrup coating - applied just prior to finishing withoutpermitting the tablets to become as dusty as the previous two syruping stage.

4. Finishing - This initiated when the desired colors is attained.

Three or four coats of regular syrup are applied rapidly without permitting the the tablet bed to become dusty.

5. Polishing

- Is done in canvas polishing pan by allowing the coated tablets to roll in wax solution until high luster is produced.

Are mainly of historic importance since chocolate was once used to color and coat compressed tablets. Today, chocolate has been replaced by the other chocolate like iron oxides to stimulates the chocolate color.

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Are compressed tablets coated with a thin layer of a water-insoluble polymeric substances capable of forming a film over tablet. The film coat is usually colored.

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Advantages over Sugar Coated Tablets1. It is more durable 2. Less bulky 3. Less time consuming to apply/ reduction in coating time/material cost 4. No significant increase in tablet weight 5. No undercoat or water proof coat required 6. Resistance to chipping and cracking 7. Allows monogramming identification of product 8. Provides effective protection to light, air and moisture 9. Pharmaceutically elegant 10. Provides the opportunity to use non-aqueous coating solutions

rapid dissolving tablets or RDT are characterized by disintegrating or dissolving in the mouth within 1 minute, some within 10 seconds ( Claritin Reditabs Loratadine ) designed for children and the elderly, patient with difficulty in swallowing tablets liquefy on the tongue, and the patient swallows the liquid

EFFERVESCENT TABLETSThese are prepared by compressing granular effervescent salts or other materials having the capacity to release gas when in contact with water.

DISPENSING TABLETSMight be better termed compounding tablets . Since they are used by the pharmacists in compounding and are never dispensed as such to the patient.

Characteristics: 1. Contain relatively large amount of highly potent drugs substances 2. The diluent or base of the tablet is usually water soluble to permit the preparation of clear aqueous solutions. 3. Dispensing tablets may be prepared by either molding or compression. 4. Disintegrating agents water-insoluble lubricants, colorants, flavorants, and coating are not used in the preparation of dispensing tablets.

NOTE: These tablets are no longer used today due to potential hazards.

Techniques to prepare the RDT1.Lyophilization - Zydis by R.P. Echerer 2.Soft direct compression - Wow-tab by Yamanouchi Shaklee Pharma 3.Other method - Quicksolv by Janssen

CHARACTERISTICS OF RDTs tablets are prepared using water-soluble excipients to wick water into tablet for rapid dissolution and disintegration no standards that define RDT, but one possibility is dissolution in the mouth within approximately 15 to 30 seconds; anything slower would not be categorized as rapidly dissolving Disadvantages and difficulties in formulating RDTs: drug loading, taste masking, friability, manufacturing costs, and stability of the product drug loading = is incorporation of the drug into dosage forms taste masking = since dissolved in the mouth, taste must be covered, either (1) flavoring technique, (2) microencapsulation or nanoencapsulation friability = is an inherent problem in RDTs, since dissolve instantly, it may be quite friable, making it more firm and less friable may increase dissolution time.

Lyophilized Foam Zydis was the first entry into the RDt Prepared by foaming a mixture of gelatin, sugars, drug, and any other components and pouring the foam into a mold. the mold also serves as the unit dose dispensing package, the foam is lyophilized and packaged Claritin (loratadine) rapidly disintegrating tablet (Reditabs) contain 10 mg of micronized loratadine in a base containing citric acid, gelatin, mannitol, and mint flavor formed with Zydis technology Claritin Reditabs are blister packaged tablets that should be stored in a dry place at 20 to 250C.They should be used within 6 months of opening the laminated foil, each foil pouch contains one blister card containing 10 individually sealed tablets. Examples: (Zydis technology) : Maxalt-MLT (Merck), Zofran ODT (GlaxoSmithKline), and Zyprexa Zydis (Eli Lilly) tablets

Compressionin 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 Example: Dimetapp ND Orally Disintegrating Tablet (Non-DrowsyAllergy Tablets) Using DuraSolv and OraSolv technologies - Tempra Quicklets: acetaminophen 80 mg, aspartame, citric acid, D&C Red No.27 Lake, FD&C Blue No.1 Lake, flavor, magnesium stearate, mannitol, potassium carbonate. Another examples: Alavert; NuLev; Remeron SolTabs; Triaminic Softchews; Zomig Rapidmelt Using Flashtab technology: Excedrine QuickTabs Using Wowtab technology: by Yamanouchi Pharma Benadryl Fastmelt

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sometimes called controlled release (CR) tablets are designed to release their medication is a predetermined manner over an extended period.

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also called vaginal inserts, are uncoated bulletshaped or ovoid tablets inserted into the vagina for local effects prepared by compression and shaped to fit snugly on plastic inserter devices contain antibacterials for the treatment of vaginitis caused by Haemophilus vaginalis or antifungals for the treatment of vulvovaginitis candidiasis caused by Candida albicans(click to return)

Quality Standards and Compendial Requirements 1. Tablet Weight and USP Weight Variation Test to yield the desired weight and content to have dosage form uniformity by weight variation 10 tablets are weighed individually and the average weight calculated and assayed 2. Content Uniformity 85% to 115% of the label claim and the standard deviation is less than 6%. 3. Tablet Thickness tablet thickness maybe measured by hand gauge during production or by automated equipment 4. Tablet Hardness and Friability are used to measure the degree of force (in kg, pounds, or in arbitrary units required to break a tablet. A force of about 4 kg is considered the minimum requirement for a satisfactory tablet durability - use of a friabilator - determines the tablets friability, or tendency to crumble, by allowing it to roll and fall within the drum

The tablets are weighed before and after a specified number of rotations and any weight loss determined Resistance to loss of weight indicates the tablets ability to withstand abrasions in handling, packaging and shipment. A maximum weight loss of not more than 1% generally is considered acceptable for most product

5. Tablet Disintegration.

tablet disintegrating apparatus = the tablets is placed in each test tubes of the basket, and through the use of mechanical device, the basket is raised and lowered in the immersion fluid at 29 to 32 cycles per minute, the wire screen always below the level of the fluid disintegration defined = that state in which any residue of the unit, except fragments of insoluble coating or capsule shell, remaining on the screen of the test apparatus is a soft mass having no palpably firm core tablets must disintegrate within the times set forth in the individual monograph, usually 30 minutes; but 2 minutes for nitroglycerin up to 4 minutes for buccal tablets

5. Tablet DissolutionReasons/Importance1. It guides formulation and product development toward product optimization 2. Manufacturing may be monitored by dissolution testing as a component of the overall quality assurance program 3. Consistent in vitro dissolution testing ensures bioequivalence from batch to batch 4. It is a requirement for regulatory approval of marketing for products registered with the FDA/BFAD

Predicting the likelihood of achieving a successful in vivo-vitro correlation (IVIVC). Considered are drugs determined to have 1. High solubility and high permeability 2. Low solubility and high permeability 3. High solubility and low permeability 4. Low solubility and low permeability

Dissolution Testing Devices

Vessels are surrounded by a warm water bath to maintain biologic al temperature for up to 96 hours Stirring rods are used to simulate biological contractions & mix ing Ports for monitoring pH, temp Dosage form must sit in the bottom of the vessel, if it floats, is must be fixed to the bottom of the vessel

Weighing and Blending mixed the active ingredient, diluent or filler, and disintegrating agent by mechanical powder blender or mixer until uniform Filler = lactose, microcrystalline cellulose, starch, powdered sucrose, calcium phosphate; the choice is based on experience and compatibility Example: calcium salts must not be used as fillers with tetracycline antibiotics because of an interaction between 2 agents that results in reduced tetracycline absorption from GT Lactose are preferred because of its solubility and compatibility Disintegrating agents = croscarmellose, corn and potato starches, sodium starch glycolate, sodium carboxymethylcellulose, polyvinyl polypyrrolidone (PVP), alginic, etc. Croscarmellose (2%) and Sodium starch glycolate (5%) are often used because of their high water uptake and rapid action; Sodium starch glycolate swell up to 300% of its volume in water Preparing the Damp Mass a liquid binder is added to the powder mixture to facilitate adhesion of the powder particles a damp mass resembling dough is formed and used to prepare the granulation

Binding agent= povidone, an aqueous preparation of cornstarch (10-20%), glucose solution (25-50%), molasses, methyl cellulose (3%), carboxymethylcellulose and microcrystalline cellulose care must be exercised not to overwet = too hard for proper tablet formation; underwetting = too soft and tend to crumbleScreening to damp Mass Into Pellets or Granules

wet mass is pressed through a screen (usually 6 to 8 mesh) to prepare the granules. This may be done by hand or with special equipment that prepares the granules.Drying the Granulation

granules may be dried in thermostatically controlled ovens that constantly record the time, temperature, and humidity.Sizing the Granulation by Dry Screening

after drying, the granules are passed through a screen of a smaller mesh than that used to prepare the original granulation

size depends on the punches to be used the smaller the tablet to be produced, the smaller the granules screens of 12 to 20 mesh size are generally used for this purpose Adding Lubrication and Blending after dry screening, a dry lubricant is dusted over the spread-out granulation through a fine mesh screen Lubricants = improve the flow of the granulation in the hopper to the die cavity, they prevent adhesion to the punches and dies during compression; they reduce friction between the tablet and the die wall during the ejection of the tablet from the machine; they give a sheen to the finish tablet Example of lubricants = magnesium stearate, calcium stearate, stearic acid, talc, and sodium stearyl fumarate. Magnesium stearate is commonly used. Quantity of lubricant = ranges from 0.1 to 5% of the weight of the granulation All -in-One Granulation Methods technologic advances now allow the entire process of granulation to be completed in continuous fluid bed process, using a single piece of equipment, the fluid bed granulator

Steps of Fluid Bed Granulator 1. Preblending the formulation powder, including active ingredients, filler, disintegrants, in a bed with fluidized air 2. Granulating the mixture by spraying onto the fluidized powder bed, a suitable liquid binder, such as an aqueous solution of acacia, hydroxypropyl cellulose, or povidone 3. Drying the granulated product to the desired moisture content

Another method, Microwave Vacuum processing, also allows the powders to be mixed, wetted, agglomerated, and dried within the confines of a single piece of equipment. 1. The wet mass is dried by gentle mixing, vacuum, and microwave 2. The use of microwave reduces drying time considerably, of ten by onefourth. 3. The total batch production time is usually in the range of 90 minutes. 4. After adding lubricants and screening, the batch is ready for tablet formation or capsule filling

Dry Granulation Slugging after weighing and mixing the ingredients, the powder mixture is slugged, or compressed into large flat tablets or pellets about 1 inch in diameter the slugs are broken up by hand or by mill and passed through a screen of desired mesh for sizing lubricants is added tablets are prepared by compression aspirin, which is hydrolyzed on exposure to moisture, may be prepared into tablets after slugging

Roller Compaction instead of slugging, powder compactors may be used to increase density of a powder by pressing it between rollers at 1 ton to 6 tons of pressure the compacted material is broken up, sized, and lubricated, and tablets are prepared by compression the roller compaction method is often preferred to slugging binder use in these method: methylcellulose or hydroxymethylcellulose (6-12%), which can produce good tablet hardness and friability

Tablet Granulationmachines compress a tablet formulation within a steel die cavity by the pressure exerted by the movement of two steel punches, a lower punch and an upper punch single punch tablet press describes the basic mechanical process. As the lower punch drops, the feed shoe filled with granulation from the hopper is positioned over and fills the die cavity. The feed shoe retracts, scrapes away the excessive granulation, and levels the fill in the die cavity. the upper punch lowers and compresses the fill, forming the tablet the upper punch retracts as the lower punch rises with the formed tablet to the precise level of the stage

Tablet Granulation the feed shoe moves over the die cavity, shoves the tablet aside, and once again fills the cavity with granulation to repeat the process. the tablet fall into a collection container a Rotary tablet machines equipped with multiple punches and dies operate via continuous rotating movement punches a consequences of high speed production is the increased occurrence of lamination (horizontal striations) and tablet capping, in which the top of the tablet separates from the whole because the fill material does not have enough time to bond after compression. Reduced speed remedies the problem

Direct Compression Tableting some granular chemicals, like potassium chloride, possess free flowing and cohesive properties that enable them to be compressed directly in a tablet machine without need of granulation lacking this quality - excipients include fillers, disintegrating agents, lubricants and glidants

Tablet Dedusting to remove traces of loose powder adhering to tablets following compression, tablets are conveyed directly from the tableting machine to a deduster. The compressed tablets may then be coated.

The Non-aqueous Film Coating Generally Contain The Following:1. A film former capable of producing smooth, thin films reproducible under conventional coating conditions and applicable to variety of tablet shapes. Examples: cellulose, acetate phthalate 2. An alloying substance providing water solubility or permeability to the film to ensure penetration by the body fluids and therapeutic availability of the drug. Example: polyethylene glycol 3. A plasticizer to produce flexibility and elasticity of the coating and thus provide durability. Example: Castor oil 4. A surfactant to enhance spreadability of the film during application. Example: polyoxyethylene sorbitan derivatives 5. Opaquants and colorants to make the appearance of the coated tablets handsome and distinctive. Examples: Opaquant- titanium dioxide, colorant - FD and C or DC

The Non-aqueous Film Coating Generally Contain The Following:6. Sweeteners, flavors, and aromas - to enhance the acceptability of the tablet to the patient. Examples: sweeteners - saccharin, flavors and aromas vanillin 7. A glossant - to provide luster to the tablets without a separate polishing operation. Example: beeswax 8. A volatile solvent to allow the spread of the other components over the tablets while allowing rapid evaporation to permit an effective yet speedy operation Example: alcoholic acetone mixture, for water based, colloidal coating dispersion is called AQUACOAT - contains 30% ethyl cellulose pseudolatex

The Typical Aqueous Film-Coating Formulations Contains The Following:1. Film Forming Polymer (7-18%). Examples: cellulose ether polymers, hydroxypropyl methylcellulose, hydroxypropylcellulose, and methyl cellulose

2. Plasticizer (0.5 - 2.0%) Examples: glycerin, propylene glycol, polyethylene glycol, and dibutyl subacetate

3. Colorant and Opacifier (2.5 - 8%) Examples: FD and C or D and C

4. Vehicle (100%) Example: water

Problems Attendant To Aqueous Film Coating1. Picking the appearance of small amounts of film fragments flaking from the tablet surface 2. Peeling the appearance of large amounts of film fragments flaking from the tablet surface 3. Orange peel effect - roughness of the tablet surface due to failure of spray droplets to coalesce 4. Mottling - an uneven distribution of color on the tablet surface 5. Bridging - filling - in of the score -line or intended logo on the tablet film 6. Tablet Erosion -disfiguration of the core tablet when subjected for too long a period of time to the coating solution

Are tablets with a coating which resists dissolution or disruption in the stomach but not in the intestine, thereby allowing for tablet transit that the stomach in favor of tablet disintegrations and drug absorption from the intestines.

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PROCEDURE FOR ENTERIC COATING

Capsules were automatically weighed and loaded into the coating chamber through airlock pinch valves.

Figure 1. Three-dimensional simulated drawing of tablets suspended in the coating chamber of Threethe Supercell coater during coating.

PROCEDURE FOR ENTERIC COATING

The coating dispersion was delivered using precision syringe pumps.

PROCEDURE FOR ENTERIC COATING

The capsules were coated and then discharged using a rapid vacuum e traction system.

PROCEDURE FOR ENTERIC COATING

Two different batch sizes (15 and 30 g) and two different sizes (Size 1 and 00) of capsules were evaluated. For each capsule and batch size, the capsules were coated to different theoretical coating levels (5.0 13.0%) weight gain).

PRINCIP ES OF ENTERIC DRUG PENETRATION TO THE BODY

The drugs immediately release a portion into the stomach while allowing a portion of the drug to pass into the duodenum wherein the enteric coating dissolves and the drug is thereby slowly absorbed by the intestines.

PRINCIP ES OF ENTERIC DRUG PENETRATION TO THE BODY

The unprotected portion of the drug rapidly dissolves in the stomach and that portion of the drug dose quickly enters the bloodstream.

The enterically coated portion of the drug begins to dissolve in the small intestine where a substantial increase in pH occurs to then controllably release the remainder of the active.

PRINCIP ES OF ENTERIC DRUG PENETRATION TO THE BODY

In the intestines, the enteric coating or membrane dissolves or disperses in the intestinal fluid. Depending upon the relatively pH solubility of the active agent, the percentage of total active inside or outside of the enteric coating can be adjusted so that e cess plasma drug concentrations are minimized and steady longlong-term release of the drug is ma imized.

This technique is employed in instances in which the drug substance is: 1. Destroyed to the gastric acid 2. Is irritating to the gastric mucosa 3. When by passing the stomach enhances drug absorption from the intestines to a significant extent Fluid - Bed or Air Suspension Coating This process involves the spray coating of pellets, beads, granules, powders, or tablets held in suspensions by a column of air. 3 Types: 1. Top spray 2. Bottom spray 3. Tangential spray technique - used in rotary fluid-bed coaters.

Principle: Batch fluid bed coating Top Spray

Principle: Batch fluid bed coating Bottom Spray (Wurster coating)

Principle: Batch fluid bed coating Tangential Spray (Rotor pellet coating)

Compression CoatingSimilar to the preparation of multiple compressed tablets having an inner core and an outer shell of drug material, core tablets maybe sugar coated by compression.

Gelatin Coated TabletsA recent innovation called GELCAPS, the innovator product is a gelatin-coated capsule shaped tablet. Compared to dry-filled, unsealed capsules, GELCAPS are more tamper-resistant and tamperevident.

Are generally flat, oval tablets intended to be dissolved in the buccal pouch (buccal tablet - side of cheek or between lips and gums) or beneath the tongue (sublingual tablet) for absorption through the oral mucosa.USE: provides for the absorption of the drugs that are destroyed by gastric juice and/or poorly absorbed from GIT. Characteristics: buccal administration (a progesterone tablet) are prepared to erode or to dissolved slowly while those for sublingual use (nitroglycerin tablet) dissolved very promptly to give rapid drug effects.

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Are 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. These are useful in formulations for children multivitamins tablets and for adults - antacids and antibiotics. Prepared by wet granulation and compression

Example Of Typical Chewable AntacidAluminum hydroxide Mannitol Sodium saccharin Sorbitol (10% w/v solution) Magnesium stearate Mint flavor concentrate 325.0 mg 812.0 mg 0.4 mg 32.5 mg 35.0 mg 4.0 mg

Preparation: (1) Blend the aluminum hydroxide, mannitol, and sodium saccharin. (2) Prepare a wet granulation with sorbitol solution. (3) Dry at 120 0C and screen through a 12 mesh screen. (4) Add the flavor and magnesium stearate, blend, and compress into tablets.

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do not contain disintegrants - chew the tablets thoroughly and not swallow them whole. Mannitol is used excipient in most chewable tablet; 70% as sweet as sucrose, with a cool feel in the mouth, accounts 50% or more of the weight of many chewable tablet formulations other sweetening agents = sorbitol, lactose, dextrose, crystalline maltose, and glucose, may be substituted for apart or all of the mannitol.(click to return)

Xylitol may be used in the preparation of sugar-free chewable tablets. Xylitol is sweeter than mannitol.

CHEWABLE TABLETlubricant and binders must not affect the texture or desired hardness of the tablet colorant 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

certain tablets, such as tablet triturates, may be prepared by molding the resultant tablets are very soft and soluble and are designed for rapid dissolution original fast-dissolving tablets were molded tablets for sublingual use. they generally consisted of active drug and lactose moistened with alcoholwater mixture to form a paste, then molded, dried and packaged example: nitroglycerin - placed under the tongue -to provide rapid onset of action example: testosterone - destroyed in the GT - administered sublingually for absorption to minimize the first-pass effect.

MOLDED TABLETS commercial preparation of tablets by molding has been replaced by tablet compression molded or tablet triturate still prepared on a small laboratory scale Procedure: 1. The mold is made of hard rubber, hard plastic, or metal 2. It has 2 parts, the upper part or die portion, and the lower part, containing squat, flat punches

3. The die portion is a flat plate the thickness of the tablets to be produced with 50 to 200 uniformly drilled and evenly spaced circular holes 4. The lower part of the mold has corresponding punches that fit the holes precisely

5. When the die is filled with material and placed atop the punches, the punches, gently lift the fill material from the holes to rest upon the punches for drying @ the base for molded tablets is generally a mixture of finely powdered lactose with or without a portion of powdered sucrose (5-20%). The addition of sucrose results in less brittle tablets @ In preparing the fill, the moisture is wetted with a 50% mixture of water and alcohol sufficient only to dampen the powder so that may be compacted; water= binds the powder mixture upon drying; alcohol = hastens drying 6. The upper mold is placed on a clean flat glass surface and the damp mass added by a rubbing motion. When each opening is filled completely and smoothed, top and bottom, the mold is fitted on the punch portion of the mold and pressed down, leaving the tablets raised on the pegs to dry.

TABLET COATINGREASONS:

1. Protect the medicinal agents against destructive exposure to air or humidity 2. To provide special characteristics of drug release ( enteric coatings ) 3. To provide aesthetics or distinction to the product 4. To prevent inadvertent contact with the drug substance and the effects of drug absorptionExample: Proscar tablets (finasteride) are coated for just this reasons. For treatment of benign prostatic hyperplasia Instruction: women who pregnant or may become pregnant should not come into contact with it. Drug contact can occur through handling broken tablets. If finasteride is absorbed by woman who is pregnant with a male baby, the drug has the potential to adversely affect the developing male fetus

Sugar Coating Tablets1. Waterproofing and Sealing Coats components are affected by moisture - waterproofing substance is applied ( shellac or a polymer); then subcoating of the tablet waterproofing solution ( usually alcoholic ) is gently poured or sprayed on the compressed tablets rotating in the coating pans warm air is blown into the pan during the coating to hasten the drying and to prevent tablets from sticking together 2. Subcoating after the tablets are waterproofed if needed, 3 to 5 subcoats of sugar-based syrup are applied This bonds the sugar coating to the tablet and provides rounding the sucrose and water syrup also contains gelatin, acacia or polyvinylpyrrolidone (PVP) to enhance coating when the tablets are partially dry, they are sprinkled with a dusting powder, ( mixture of powdered sugar and starch but sometimes talc, acacia or precipitated chalk ) warm air is applied to the rolling tablets, then dry, the process is repeated until desired shapes size is obtained.

3. Smoothing and Final Rounding after the tablets are subcoated, 5 to 10 additional coatings of a thick syrup are applied to complete the rounding and smooth the coating this syrup is sucrose based, with or without additional components such as starch and calcium carbonate. as the syrup is applied, the operator moves his or her hand through the rolling tablets to distribute the syrup and to prevent the tablets from sticking to one another a dusting powder is often used between syrup applications warm air is applied to hasten the drying time of each coat

4. Finishing and Coloring to attain final smoothness and the appropriate color to the tablets, several coats of thin syrup containing the desired colorant are applied in the usual manner. this step is performed in a clean pan, free from previous coating materials

5. Imprinting to impart identification codes and other distinctive symbols radiopharmaceuticals, other products because of their size, shape, texture, make imprinting technologically not feasible.

6. Polishing coated tablets may be polished in several ways

a. Special drum-shaped pans or ordinary coatings pans lined with canvas or other cloth impregnated with carnauba wax or beeswax, may be used to polish as they tumble in the pan b. Pieces of wax may be placed in a polishing pan and the tablets allowed to tumble over the wax until the desired sheen is attained. C. Light spraying of the tablets with wax dissolved in a nonaqueous solvent two or three coats of wax may be applied, depending upon the desired gloss after each coat has been applied, the addition of a small amount of talc to the tumbling tablets contributes to their high luster Example: Coated, polished, and monogrammed tablets = Premarin 0.625 and 1.25 mg

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Are small, usually cylindrical molded MTT or compressed CTT tablets containing small amounts of usually potent drugs.

Characteristics: 1. Must be readily and completely soluble in water, thus when prepared by compression a minimal amount of pressure is exerted. 2. The diluent is usually a combination of sucrose and lactose avoiding any water-insoluble material.

USES: 1. Used for oral administration of drugs and some sublingual. 2. Used in compounding procedures in the preparation of other solid or liquid dosage forms. Example: The tablet may easily inserted into capsules to provide accurate amounts of potent drugs 3. Use to fortify liquid preparations as prescribed by dissolving the appropriate number of tablets in a small portion of water the bringing the preparation to the required volume with the liquid being fortified.

Are tablets triturates for use by the physician in his extemporaneous preparation of parenteral administration.

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Also called controlled release, sustained release, prolong release, timed release, slow release, sustained action, prolong action, extended action, and rate controlled tablets or capsules are solid dosage forms designed to release the drug slowly for more prolonged drug release and sustained action.

Characteristics:1. Exhibit neither very slow nor very fast rates of absorption and excretion. 2. Uniformly absorbed from the GIT. 3. Administered in relatively small doses. 4. They possess good margin of safety. 5. Used in the treatment of chronic rather than acute conditions.

Packaging and Storage:

Stored in tight containers in places of low humidity and protect from extreme temperature. Packed with dessicant to avoid decomposition by moisture and packaged in light resistant containers.

METHODS OF PREPARATIONS 1. Dry methods a. Direct Compression b. Granulation by compression 2. Wet methods a. Wet granulation b. Special procedures/related granulation processes

Dry Granulation Method 1. Weighing of ingredients 2. Mixing of ingredients in suitable mixer blender 3. Slugging by using flat face punches 7/8 to 1 inch diameter 4. Dry screening of slugs through a mesh screen (by hand) or through a Fitzpatrick comminuting mill 5. Lubrication through a suitable blender 6. Compression into final tablets Note: Slugging has the advantage of utilizing less equipment and space than wet granulating, no binder solution and subsequent drying

DRUG

ADJUVANT

BLEND GRIND PELLET

COMPRESS LUBRICANT CRUSH

TABLET

BLEND SCREEN

Tablet Granulations Granulation is the pharmaceutical process that attempts to convert powdered materials into aggregates called granules. Granules Must Possess: 1. Fluidity: the property necessary for the transport of material through the hopper into the feed frame 2. Compressibility: the property of forming a stable compact mass when pressure is applied

Accordingly, a good tablet granulation should:1. Contain particles which approach spherical shape. 2. Present a range of particle size that resembles a normal distribution curve, with a small percentage of coarse and fine particles and with the rest in a narrow range between. 3. Have a uniform distribution of all the ingredients in the formulation. 4. Possess compressible components that will confer physical strength and form to the tablet.

Tablet Granulation

The mixture is then placed on the lower punch. The upper punch then compress the tablet at the same time taking out the air.

WET METHODIs the most widely used. The general method of preparing tablet granulation that will satisfy the physical requirements for the compression of good tablets. Disadvantages: 1. It involves several steps (separate) 2. Requires longer processing time 3. Labor cost is high

Steps Of Wet Method1. Weighing of the ingredients 2. Mixing them in a suitable mixer or blender 3. Granulation into a damp mass by the addition of a binding solution 4. Screening the mass by forcing through a 6 to 8 mesh screen 5. Drying in suitable ovens or fluid bed dryers 6. Dry screening through smaller mesh screen 7. Lubrication in a suitable blender 8. Compression into final tablets

DRUG

ADJUVANT

LIQUIDID IDS

BLEND GRIND LUBRICAN TCOMPRESS

AGGLOMERATE

PELLET

TABLET

BLEND

SCREEN

DRY

Processing Problems

1. Chipping - the separation of a small piece of tablet surface after ejection 2. Capping - the partial or complete separation of the top or bottom of a tablet from the main body 3. Lamination - the separation of a tablet into one or more distinctive layer

Factors that may cause splitting of tablets1. Excess fine or powder which entraps air in the tablet mixture 2. Deep markings on tablet punches. Many designs or scores on punches are too broad and deep. 3. Worn and imperfect punches. Punches should be smooth and buffed. 4. Worn dies. Dies should be replaced or reversed. 5. Too much pressure on the machine 6. Unsuitable formula 7. Moist and soft granulation. It will not flow into the dies, thus giving uneven weight and soft or capped tablets 8. Poorly machined punches.

Picking and StickingPicking describes the removal of material from the surface of the tablet and its adherence to the face of the punch. (same chipping). The main difference is that it occurs before the ejection of tablets. Sticking describes the adhesion of granulation to the die wall.

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REMEDIES:1. Design lettering as large as possible, particularly on punches with small diameters 2. Reformulate to produce a larger tablets

REMEDIES3. Plate the punch faces with chromium to produce smooth, non adherent face 4. Add a polishing agent such as colloidal silica 5. Add more binder or change the binder to make granules more cohesive 6. Dilution of low melting active ingredients/additives 7. Refrigeration of the press and granulation containing high concentration of low melting medicament.(e.g. stearic acid and polyethylene glycols) with high melting materials will prevent softening of the granules due to heat of compression and many increase tablet size 8. Re-dry the granulation

Reasons Of Coating Tablets1. To mask unpleasant taste 2. To improve appearance 3. To separate reactive ingredients 4. Protect components from atmospheric degradation 5. Control drug release 6. Surface modification 7. Sustained action 8. Prevent contact with the drug which is irritating/allergies

Tablet Coatings Are Classified Into Four1. Sugar coating 2. Film coating 3. Compression 4. Other new concepts a. Pan coating b. Air suspension coating c. Dip coating d. Tablet compression coating

Processes used in the application of coatingsPan coating - This process in both sugar and film coating. It makes use of coating pans provided with a hot and cold air input system and exhaust system to remove moisture and fine powder generated during the coating operation. Air Suspension Coating - This process has become one of the most dependable methods for applying film coats. The coating is atomized and applied to tablets as they are suspended inside the columnar coating and applied to means of a stream of hot air Dip Coating - Materials to be coated are usually placed in baskets and dipped into containers of coating solutions. The wet tablets are then agitated or tumbled in coating pans during drying to prevent adherence to each other. The process is repeated a number of times after each coat is sufficient dry. Compression Coating - Compression coating makes possible some special dosage forms. Two incompatible drugs may be separated by placing one in the core, the other in the coating.

Subcoatings Are Either 1. Debossed - imprinted with a mark below the dosage form surface 2. Embossed - raised above the surface of the dosage form 3. Engraved - imprinted with a code that is cut into the dosage form surface after it has fabricated Evaluation Of Tablets 1. Hardness - mechanical hardness (Strong cobb tester, Stokes Monsato) 2. Dissolution rate -knowing the length of time by which the tablet has dissolved in the media

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EVALUATION OF TABLETS 3. Friability - is tested by a Roche Friabilator which induces shock and friction of the tablet 4. Disintegration time - to assure product uniformity; 5-30 minutes is required for disintegration time 5. Weight variation - 130 mg or less - 10 %; 130134 mg - 4.5% ; 324 over - 5% allowances 6. Thickness - micrometer caliper; determination of length and width 7. Content uniformity - to detect homogeneity of the distribution of the drug content

Examples Of Some Official TabletsOfficial Tablet Commercial ProductsAcetaminophen Allopurinol Amitriptyline HCl Tylenol Zyloprim Elavil HCl

Tablet Strengths usually available325 mg 100, 300 mg 10,25,50,100, 150 mg

Category

Analgesic and antipyretic Antigout, antiurolithic Antidepressant

Bisacodyl Carbamazepine Chlorambucil Chlorpheniramine maleate Chlorpropamide Cimetidine

Dulcolax Tegretol Leukeran Chlor-Trimeton maleate Diabinese Tagamet

5 mg 200 mg 2 mg 4,8, and 12 mg 100, 250 mg 200, 300 mg

Cathartic; E. Coated Anticonvulsanr Antineoplastic Antihistamine; controlled release Antidiabetic Histamine H2 receptor antagonist

Diazepam

Valium Lanoxin

2,5,10 mg

Sedative; skeletal muscle relaxant

Digoxin

0.125, 0.25, 0.5

Cardiotonic

Examples Of Some Official TabletsOfficial Tablet Commercial ProductsDimenhydrinate Dramamine

Tablet Strengths usually available50 mg 25, 30 mg

Category

Antinauseant Bronchodilator Vasoconstrictor

Furosemide Griseofulvin Haloperidol

Lasix Fulvicin U/F Haldol

20,40, 80 mg 250,500 mg 0.5,1,2,5,10,20 25,50,100 mg 300,400,600, 800 mg

Diuretic; antihypertensive Antifungal Tranquilizers Diuretic, antihypertensive Analgesic, Antipyretic Antidyskinetic Antivertigo Narcotic analgesic Sedative,hypnotic Antihypertensive

Hydrochlorothiazide Hydro-Diuril Ibuprofen Levodopa Meclizine HCl Meperidine HCl Meprobamate Methyldopa Motrin

Larodopa Antivert Demerol Equanil Aldomet

100,250,500 12.5, 25,50 50 and 100 mg 200, 400 mg 125,250,500

Examples Of Some Official TabletsOfficial Tablet Commercial Products Metronidazole Nitroglycerin Penicillin V Potassium Prednisone Prochlorperazine Maleate Propanolol HCl Inderal 10,20,40,60,80 90 mg Antianginal; Antiarrhythmic Antihypertensive Sulindac Clinoril 150 and 200 mg Antirheumatic Antiinflammatory Terbutaline sulfate Brethine Tolbutamide Warfarin Orinase Coumadin 2.5 and 5 mg 250 and 500 mg 2, 2.5, 7.5, 10 Antiasthmatic Antidiabetic Anticoagulant(click to return)

Tablet Strengths usually available 250, 500 mg 0.150,0.30,0.4,0.6 250, 500 mg

Category

Flagyl Nitrostat Pen Vee

Antiamebic, antitrichomonal Anti-anginal Antibacterial

Deltasone1 mg Compazine

Adrenocorticoid 5,10,25 mg Antiemetic

Are small round dosage forms containing a medicinal agent and intended to be administered orally. Pills may be coated or uncoated Today pills have largely replaced by compressed tablets and capsules. Example: Hexylresorcinol pills NF as antihelmintic. .

Characteristics:1. Adhesiveness - retain shape 2. Firmness to retain shape; hold its shape when molded into pills 3. Plasticity - capable of being worked upon but not sticky enough to our hand, tools or mixing machine 4. Disintegration - disintegrates readily in gastric or intestinal fluids TYPES: 1. Compressed Pills 2. Dispensing Pills

Four Classes Of Pills According To Weight 1. Parvules - potent substance with coloring agent, small pills; 20 mgless 2. Granules - it contain sugar; 20 mg to 60 mg 3. Pills - comes in variety of sizes, shapes, coatings and colors; 60-500 mg 4. Boluses - for veterinary use; big pills; 700 to 2000 mg

OTHER SOLID DOSAGE FORMS

1. Lozenges/ Pastilles or Troches

-

Are disk-shaped, solid dosage forms containing a medicinal agent and generally a flavoring substances and intended to be slowly dissolved n the oral cavity or localized effects. Examples: Cepachol, Strepsils, Fishermans Friend, Dequadin

Classification Of Ingredients1. Active ingredient - antiseptic, local anesthetics, antibiotic 2. Flavored base - hard sugar candy, glycerinated gelatin Methods Of Preparation 1. Compression - for heat labile active ingredients 2. Hard candy base - for heat labile stable active drug

2. Cachets or Konseal or Wafer Capsules are related to capsules, in as much as they provide an edible container for the oral administration of solid drugs, cachets were formerly used in pharmacy. They vary in size, from 3/4 to 1/8 of an inch in diameter and consisted of 2 concave pieces of wafer made of flour and water.

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3. Pellets or Inserts are small, sterile cylinders about 3.2 mm in diameter by 8 mm in length which are formed by compression from medicated masses. They are used by implantation.Examples: Testosterone, estradiol, ordesoxycorticosterone pellet desired for prolonged and continuous absorption. Norplat (Wyeth-Ayers)

4. Vaginal or Inserts

are specially formulated and shaped tablets intended to be placed in the vagina by special applicators, where the medication is released, generally for localized effects

5. Lollipops - Fentanyl Actiq is a raspberry lollipop that differs from Fentanyl Oralet. It is a sugar-base lozenge on a stick and contains fentanyl citrate . Actiq is the first product designed to aid in controlling breakthrough pain in cancer