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57 Cards in this Set
- Front
- Back
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Tablet dosage form
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*Definition: Solid dosage form containing drug substances with or without suitable diulents, which are prepared either by compression or molding methods.
*Most popular dosage forms, about one-half of all rx dispensed are tabs. *Tabs vary in size, shape, weight, hardness and thickness. *Mostly intended for the oral administration of drugs, sometimes SL and BUCCAL. |
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Advantages of tablets:
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*Accuracy of dose
*Ease of administration *Industrial manufact. of tabs is both rapid and inexpensive *Tabs are easy to package, ship, dispense *Tabs are more stable than liquid preparations *Marked for east identification *May be coated to hide the bad taste or odor of a drug *Release rate of drug can be tailored for specific needs (CR, XR) |
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Disadvantages of tablets:
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*Some drugs resist compression to low-density character
*Drugs eith poor wetting, slow dissolution properties, intermediate to large dosages: affect bioavailability adversely *Bitter tasting, objectionale odor, sensitive to oxygen or atmosphere require encapsulation, or coating *Tabs may be too big for children *Disintegration and dissolution is the rate limiting step for drug action and hence not used when the action is promptly needed. |
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Characteristics of ideal tabs:
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*Free of defects such as chips, cracks, discoloration and contamination
*Have the strength to withstand mechanical stresses of production. *Stable over time *Release medicinal agents in predictable and reproducible manner. |
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Tabs types and classes:
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*Tablets are classified by their route of administration, drug delivery system and form and method of manufacture
-Compressed tabs --Multiply compressed tabs -Repeat action tabs -Enteric coated tabs -Gelatin coated -Film-coated tabs -Air suspension-coated tabs -Chewable tabs |
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Tablet types and classes:
Tabs used ONLY in the Oral Cavity: (No ingestion): |
*Buccal
*SL tabs *Lozenges |
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Tablets used to prepare solutions:
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*Effervescent tabs
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Tabs for Oral Ingestion:
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*Designed to be swalloed intact, with the exception of chewable tabs
*Can be coated to: -Mask drug's taste, color or odor -Control drug release -Protect the drug from the stomach's acid environment (Enteric) -Incorporate another drug, providing dequential release or avoiding incompatibilities -Improve appearance |
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Compressed Tabs: ALL
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*Formed by compression
*No special coating *Made from powdered, crystalline, or granular materials, alone or in combo with such excipients as binders, disintegrants, diluents and colorants. |
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Multiple compressed tabs:
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*Are layered or compression coated (tab-within-a-tab)
*Subjected to more than a single compression: -to get a multiple-layered tab or a tab-within-a-tab -inner tab being the core and the outer portion being the shell |
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Reasons for seperating medicinals in a Mult-compressed tab:
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*Drug incompatibility
*Providing drug release in two or more stages *Unique appearance of a mult-layered tab *Each portion of fill is colored differently to prepare a mult-colored as well as a mult-layered tab *For tablets with an inner core, special equipment is needed |
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Repeat action tabs: Can be Mult-Compressed tabs
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*Usually contain 2 single doses of a med, one fore immediate release and the second for delayed release
*Outer layer or shell provides an initial drug does that rapidly disinegrates in the stomach *The inner layer (or inner tab) is comprised of components that are insoluble in gastric media but soluble in intestinal media Ex: Repetabs, Ambien CR |
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Enteric coated tabs:
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*Only break down in basic median
*Tabs with a coating, which resists dissolution or disruption in the stomach *act in the intestines, thereby allowing tab transit through the stomach intact only to disintegrate and get absorded from the intestines. |
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Film-coated tabs:
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*Compressed tabs coated with a thim layer of water-insoluble or water soluble polymer (Ex: hydroxypropyl methylcellulose, ethylcellulose, povidone, PEG)
*The film is generally colored, more durable, less bulky, and less time comsuming to apply than sugar coating *Increases tab weight by only 2-3% (as opposed to 50% increase in size of sugar coated tabs) *Provides increased formulation efficiency, increased resistance to chipping and increased output |
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Air-suspension coated tabs:
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*As the coating solution enters the system, it is rapidly applied to the suspended, rotating solids (Wurster Process). Rounding coats are applied in less than 1 hour
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Chewable tabs:
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*Disintegrate smoothly and rapidly when chemed or allowed to dissolve in the mouth, yielding a creamy base (from specially colored and flavored mannitol)
*Especially useful in formulations for children and are commonly used for multivitamin tabs *They are also used for some antacids and antibiotics |
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Buccal and SL tabs:
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*Generally flat, oval tabs, dissolve in the buccal (check) pouch (Buccal tabs), or beneath the tongue (SL tabs) for absorption through the oral mucosa
*Useful in providing for the absorption of drugs that are destroyed by the gastric juice and/or poorly absorbed from the GI tract *Important examples are Nitro and many steroid hormones *Buccal tabs (Ex: progesterone) are prepared to erode or to dissolve slowly *SL tabs (Nitro) dissolve very promptly to give rapid drug effects *Troche, Lozenges and Dental Cones: dissolve more slowly in the mouth and provide primarily local effects. |
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Effervescent tabs:
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*Prepared by compressing granular effervescent salts (Ex: citric acid, tartaric acid, sodium bicarb)
*Have the capacity to release CO2 gas when in contact with water *Commercial alkalinizing analgesic tabs are frequently made to effervesce to encourage fast dissolution (Ex: Alka Seltzer) |
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Tab Ingredients:
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*In addition to the active, or therapeutic agents, tabs contain a number of inert material called excipients
*They may be classified according to the part they play in the finished tab *Some excipients impart satisfactory processing and compression characteristics to the formulation, whereas others help to give additional desirable physical characteristics to the finished tab *These include 1. diluents 2. binders 3. glidants and lubricants 4. disintegrants 5. colors, and in the case of chewable tabs 6. flavors and 7. sweetening agents |
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Diluents (FILLERS):
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*Inert substances
*Added to the tab formulation to increase the bulk of the tab to a practical size for compression and administration *Most compressed tabs have a total weight of at least 250 mg. *Commonly used tab diluents include: Lactose, Calcium subfate and Microcrystalline cellulose (Avicel)*** *Equal parts of Lactose and dicalcium phospate are frequently used. Only used when drugs can be affected by other diluents |
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Selection of diluent:
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*Basis of experience and cost
*Its effect on the drug (Ex: Calcium salts (dicalcium phospate, calcium sulfate) form insoluble complexes with tetracycline and should not be used as a diluent for this drug. *Water-soluble diluents (lactose) are used for drugs of low water solubility to avoid possible bioavailability problems |
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Diluents: Chewable tabs
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*MANNITOL most commonly used dilunet in chewable tabs
-It has a sweet taste -chemically stable -readily undergoes disintegration when chewed (dissolution with negative heat solution=cooling effect) |
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Binders or Adhesives:
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*Defined as agents used to impart cohesive qualities to the powder mixture
*To ensure that the tab remains intact after compression and to form granules of the drug powder mixture |
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Common binder ex:
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*Starch paste-commonly used (10% w/w aqueous, disperse cold and warm=paste)
*Gelatin solution-These solutions should be prepared fresh (to avoid growth of mold) and must be used while warm (hydrate cold and warm to yield a solution) *Glucose solution-corn syrup solution **Methylcellulose-soluble in cold H2O but not in hot H2O **Sodium carboxymethylcellulose **Synthetic while *Natural |
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Binders cont:
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*Ethylcellulose-insoluble in water but may be used as a binder when dissolved in alcohol
*Thus, it is commonly used as a binder for moisture sensitive drugs (ASA, anitbiotcs, effervecent) However, since it is not water soluble, it may decrease the dissolution rate of the drug *Microcrystalline cellulose (Avicel)-used in dry form for direct compression, expensive-Has dual action-diluent and binder |
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BINDER amount:
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*Usuallt btn 5-15% since it will have considerable influence in the hardness of the final tab
*Too much binder (over 15%) -tab will be very hard and resist disintegration after ingestion. -will cause excessive wear and tear of the punches and dies (parts of tab machine) * Too little binder (below 5%) -enhances the possibility if making a soflt tab, one that crumbles upon packaging *Amount of binder is usually determined by trial and error |
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Tab Binder:
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*Gelatin-causes fast dissolution becase it imparts hydrophilic charect. to the hydrophobic drug surface
*Na CMC is converted to a less soluble form in acid environment *PEG forms a complex with poor solubilty |
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Lubricants:
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*Prevent adhesion of the material to the surface of the dies and punches
*reduce interparticle friction *facilitate the ejection of the tab from the die cavity and may improve the rate if flow if the tab granulation |
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Lubricants:
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Talc, Magnesium stearate, calcium stearate,=hydrophobic, sodium lauryl sulfate (SLS)=hydrophillic=better dissolved
*used in concentraion less than 1% *Lubs in most cases are hydrophobic materials. Poor selection or excessive amounts can result in "waterproofing" the tabs, resulting in poor disintegration and dissolution of the drug substance |
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Action of Mg Stearate:
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*Hydrophobic lubs such as mg stearate, talc, Al stearate decrease the effective dru-solvent interfacial area by changing surface characteristics of the tab thus reducing wettability and prolonging disintergration
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Action of SLS:
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*The enhancing effect of SLS (water soluble surfactant) was due to increased wetting and better solvent penetration into the tabs and granules as a result lowering of interfacial tension btn solid surface and solvent
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Glidants:
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*It is a substance that improves the flow characteristic of a powder mixture
*These materials are always added in the dry state just prior to compression *COLLOIDAl silicon dioxide is the most commonly used glidant and is generally used in low concentraio of 1% or less *TALC is also used and may serve the dual purpose as lubricant/glidant |
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Disintegrants:
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*It is a substance or a mix of substances, added to the tab to facilitate its break up or disintegration after administration
*These have been chmically classified as starches, cellulose, algins, gums and cross-linked polymers |
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CORN STARCH POWDER:
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*Most commonly used disintegrant
*Safe,cheap, and functions well as a disintegrant *Dry powder=disintegrant, add water=paste which is a binder-dual opposite action *Starch has a great affinity for water and swells when moistened, facilitating the rupture if the tab matrix-capillary action rather than swelling as the cause for action of starch? *Concentrations of 5-15% are used 5% commonly or 10-15% for ODT tabs |
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"Super disintegrants"
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*The name comes from low concentration levels 2-4% at which they are completely effective
*Ex: Croscarmelose (A cross-linked cellulose), Crospovidone (cross-linked) and Sodium Starch Glycolate also called Explotan (a modified starch molecule |
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Sweetening/Flavoring agents:
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*In addition to the sweetness which may be afforded by the diulent of the chewable tbs, mannitol or lactose, articial sweeteners may also be used
*Aspartame (SEARLE) may be applicable to pharmaceutical formulations |
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Coloring agents:
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Functions of color:
-making the dosage form more esthetic in appearance -helps the manufacture to control the product during its preparation -Ex: FD&C Red No 3, FD&C Yellow No 5 |
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Method of adding color dye:
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1-dissolve the dye in the binder solution prior to granulation (wet method).
-However, the color can migrate (creep) during granulation drying, resulting in unevenly colored granules and mottled (spotted tabs) --Solution: drying the granules slowly at low temp and by stirring the granules during drying (or use fluid bed dryer) *Mottling* becomes more pronounced as the dye concentration increase, hence use pastel shades (low dye concentration *The quanity of dye used must be measure very carefully to avoid batch to batch variation in color *This is especially important since the coloring agent normally only composes 0.00005-0.001% w/w of the tab mis, need a few drops |
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Tab Evaluation and Control:
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**General Appearance
*This is important for: -consumer acceptance -lot-to-lot uniformity -tab to tab uniformity -monitoring of the manufacturing process *tab appearance includes visual id and overall appearance *Control of appearance includes measurement of : size, shape, color, odor, taste, surface, texture, physical flaws, consistency and legibility of markings |
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Quality Assurance:
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* tab appearance
* tab weight (USP) -up to 130 mg, 10% -130-324 mg, 7.5% ->324mmg, 5% *content uniformity |
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Tab hardness:
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*Tabs must be suffieiently hard enough to resist breakage during shipping and handling, but not so hard that they resist disintegration in the GI fluids
*The hardness of a tab mainly depends in the amount of pressure used to compress the granules, which is adjustable *The higher the pressure used the harder the resulting tab. (also binder type and amount, granulation method and granule hardness play a factor *Oral compressed tab 4-8kg, chewable 3 kg *Hardness determination is also made throughout the tab run to determine if any further adjustments in pressure are required, as is usually the case *So the correct tab hardness is maintained within a batch of tabs and from batch to batch of tabs |
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How to determine hardness:
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*Different instruments are available for usw in the determination of tab hardness
*All the instruments measure the force required for a plunger to break a tab that is placed on its side -Instruments vary from small hand held models (pfizer pliers) to push button controlled electrical models |
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Tab Friability:
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*A better measurement of a tabs ability to withstand shipping and handling
*=the tab tendency to crumble, chip or wear during shipping and handling, which results in tab weight loss *Cotton is commonly placed on the top of tab containers to keep the tablets tightly packed so that the tabs don't bump against each other too much during shipping *Excessive tab friability results in tab powder or fragments in the bottom of the container *Generally measure using a Roche Friabilator -A certain # of tabs (10-80) are weighed and placed in a plastic rotation drum, the tabs are tumbled for a length of time and the tabs are removed and dusted and reweighed to determine weight loss. *Manufact. may just ship tabs back and forth to evaluate *less than 1% damage ia acceptable |
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Tab Weight variation test:
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*Tabs containing relatively non-potent drugs must pass a weight variation test
*may be due to poor granule flow into the dies *Official limits for variation in individual tabs weight from the average tab is given in USP *coated tabs should be subjected to this test prior to coating to eliminate any weight variation due to variation in coating thickness *USP standard is for tabs contain 50 mg or MORE of drug |
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Content uniformity
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*To ensure that every tab includes the same amount of drug substance from batch to batch-usp is for tabs with 50 mg and less.
*Test=10-20 tbs are ground and dissolved in suitable solvent. Spectroscopic or chromatographi methid to assay *Range of ative drug 90-110% label claim |
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Tab Disintegration:
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*all tabs must pass a disintegration test before they are place on the market.
* So that the drug is fully absorped in GI it must disintegrate and discharge the drug to the body fluids for dissolution *also important for tabs like antacids and antidiarrheals that aren't absorped but act locally on the GI tract *Test uses a disintegration apparatus--read more *Disintegration time=the time required for the tab to break up into particles small enough to pass through the 10 mesh screen and out the tube |
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Max allowable disintegration time:
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*Uncoated tabs = 30 mins
*SL-Nitro tabs =2 mins *Buccal =4 hrs *Coated tabs = 35 mins, 5 mins to soak in water. *Enteric = 1 hr |
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Dissolution test:
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*measures the amount of time required for a specific percent of the tab active ingredient to dissolve in dissolution medium
**this test is intended to be a more accurate indication of the bioavailbility of a drug product than disinteg. since the tab undergoes dissolution before it can be absorped *All tabs have to pass a diss test |
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Choice of dissolution media:
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*Stimulate drug release in human GIT
*Recommended media: -aqueous buffers 1-8 pH range -HCL to stimulate gastric fluid -phosphate/acetate buffer in pH 4.6-4.8 -temp 37C |
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Paddle:
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*default apparatus-must commonly used
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Basket:
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*Preferred over the paddle for enteric coated or beads
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Reciprocating cylinder:
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*used for low solubility compounds when surfactant concentraion is excessive
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Flow-through:
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*Enteric coated dosage forms, low solubility compounds other strategies requiring a switchover in media
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Tabs Machines:
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*Two types
-Single punch-100tab/min -Multi-station rotary press-10,000tab/min |
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Five basic components of tab machines
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*Hopper-stores powder for compression
*Feed frame-distributes powder to dies *Dies-controls shape and size *Punches-compacts material wn dies *Cams-synchronize movement of punches |
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Tab Manufacture:
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*Direct compression
*Wet granulation *Dry Granulation |
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Why coat tabs?
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*protection of medicinal agents
*masking taste of drug *special charact: enteric coating *esthetics and distinction of product-looks good *prevent contact w/drug sustance Ex. Proscar *Improve Mechanical integrity (Increase resistance to mishandling( |
