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186 Cards in this Set
- Front
- Back
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2 of the most popular solid dosage forms?
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tablets and capsules
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What percentage of U.S.'s drugs are formulated in oral dosage forms?
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80%
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What is a tablet?
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a solid pharm. dosage form containing drug subst.s with or without suitable diluents
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Describe physical traits of tablets?
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vary in size, shape, wt.,hardness, thickness, disintegration, and dissolution characteristics
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Tablets are mostly used how?
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orally
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How are tablets primarily prepared?
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by compression with a very few prepared by molding
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4 pros of tablets?
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1. cheap to make
2. easy to make and ship 3. accurate dosing 4. easy to administer |
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2 general ingredients of tablets?
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1. active ingredient
2. excipients (adjuvants) |
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What is an adjuvant?
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a component added to an active ingredient that has a special function (to form a tablet)
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What is a diluent?
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(filler)...adds bulkiness to the formulation to prep. tablets of desired size
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4 examples of tablet diluents?
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1. lactose
2. sucrose 3. mannitol 4. starch |
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What are binders?
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(adhesives)...promotes adhesion of the particles in the formulation, helps in granulation and maintain integrity of the final tab.
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3 ex.s of binders?
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1. starch paste
2. alcohol 3. water |
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What is a disintegrant?
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promotes the breakup of the tablet (and capsule "slugs") into smaller frag.s in an aqueous environ. thereby increasing the available surface area and promoting a more rapid release of the drug substance
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2 examples of disintegrants?
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1. pregelatinized starch
2. microcrystalline cellulose |
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What are super disintegrants?
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disintegrate in less time...b/c of the increased demands for faster dissolution reqt.s, these are now available
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3 super disintegrants?
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1. modified starches
2. cross-linked polyvinylpyrrolidone 3. modified cellulose |
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Describe the super disintegrant "modified starches"?
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-sodium carboxymethyl starch...chemically treated potato starch...ie. sodium starch glycolate
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Describe the super disintegrant "cross-linked polyvinylpyrrolidone"?
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water insoluble and strongly hydrophilic...so absorbs water and can bursts...ie. crospovidone
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Describe the super disintegrant "modified cellulose"?
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internally cross-linked form of sodium carboxymethyl cellulose...ie. Ac-Di-Sol (accelerates dissolution)
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What are lubricants?
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agents added in small qtys to tablet and capsule formulations to improve certain processing characteristics
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3 roles identified with lubricants?
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1. true lubricant role
2. anti-adherent role 3. glidant role |
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What is the True-Lubricant Role of lubricants?
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to decrease friction at the interface between a tablet's surface and the die wall during ejection and reduce wear on punches and dies
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What is the Anti-adherent role of lubricants?
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prevent sticking to punch faces or in the case of encapsulation
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What is the Glidant role of lubricants?
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enhance product flow by reducing interparticulate friction
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5 examples of lubricants?
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1. calcium stearate
2. zinc stearate 3. starch 4. talc 5. magnesium stearate |
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Which is one of the most widely used lubricants in the pharmaceutical industry? Why is a very low concentration reqd when using it?
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Magnesium stearate ...it is hydrophobic, so just use a small concentration or tablet will not dissolve
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Describe the process of tablet dissolution?
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1. Tabs (or caps) EITHER disintegrate to form granules or aggregates OR they dissolve into solution and then can go on to be absorbed
2. Granules or aggregates EITHER deaggregate into fine particles OR the dissolve into solution and can go on to absorption 3. The fine particles dissolve into solution and then can go on to absorption |
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What is the rate limiting step of the dissoltion process?
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the dissolution of drug into solution...this is reqd for drug to absorb
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Where does dissolution occur typically?
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in the stomach or intestinal fluid
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12 types of tablets?
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1. compressed tabs
2. multiple compressed tabs 3. sugar coated tabs 4. film coated tabs 5. gelatin coated tabs 6. enteric coated tabs 7. buccal and sublingual tabs 8. chewable tabs 9. effervescent tabs 10. molded tabs 11. vaginal tabs 12. rapidly dissolving tabs (RDT) |
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What does RDT stand for?
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rapidly dissolving tabs
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What does buccal refer to?
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cheek
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What does sublingual refer to?
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under the tongue
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What are the most common type of tablets?
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compressed tablets
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General process for preparing compressed tabs?
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1. Active ingredients and Adjuvents (excipients) are mixed and granulated
2. drying 3. pressing 4. coating (if applicable) 5. packaging |
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What are adjuvents?
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excipients, or ingredientss to bind active elements together
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What are multiple compressed tabs?
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tabs subjected to more than single compression
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What do multiple compressed tabs result in?
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a tablet core and shell, or layered tabs
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What is the purpose of multiple compressed tabs?
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to solve incompatibility issues (2 incompat. drugs in one tab) or for controlled release
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Multiple compressed tabs have a unique what?
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appearance
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What do sugar coated tabs have?
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water soluble sugar layer that quickly dissolves in the GIT
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2 advantages of sugar coated tabs?
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1. protection from the environement
2. mask taste and odor |
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What are 2 diadv.s of sugar coated tabs?
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1. time consuming (long process, many coats applied)
2. increase tab wt. and shipping costs |
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6 steps of sugar coating tablet preparation?
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1. waterproofing
2. subcoating 3. smoothing and final rounding 4. finishing and coloring 5. imprinting 6. polishing |
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Explain the 1st step of sugar coating, waterproofing?
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takes place in a coating pan...done to protect moisture...includes 1 or more layers...shellac or polymer in alcohol (poured or sprayed)...warm air for drying
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Explain the 2nd step of sugar coating, subcoating?
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involves 3-5 coats...sugar based syrup with gelatin, or acacia, or PVP...rounding the tab and bond the sugar coat to the tab.
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Describe the 3rd step of sugar coating, smoothing and final rounding?
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5-10 addnal coats or thick syrup...mainly sucrose based...warm air
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Describe the 4th step of sugar coating, finishing and coloring?
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coat with thin syrup and color to attain final smoothness
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Describe the 5th step of sugar coating, imprinting?
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printed, or engraved
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Describe the 6th and final step of sugar coating, polishing?
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carnuba wax and/or beeswax
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Describe thin-coated tablets?
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have a thin skin-tight coating of a plastic like material...have the same wt., shape, and size of the original uncoated tab
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Film coated tabs are resistant to what?
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destruction
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The coating solution of film coated tabs is either ? or ?.
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aqueous or nonaqueous
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The film coating of tabs takes place in a what?
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coating pan
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The solvent for an aqueous film coating vs nonaqueous?
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aqueous = water
nonaqueous = alcohol-acetone |
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The film forming polymer of an aqueous film coating vs nonaqueous?
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aqueous = methylcellulos
nonaqueous = cellulose acetate phthalate |
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What does a plasticizer do?
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increases flexibility
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The plasiticizer of an aqueous vs. nonaqueous film coating?
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aqueous = glycerin
non = castor oil |
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Gelatin coated tabs facilitate what?
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swallowing
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Where are gelating coated tabs mainly seen?
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prenatal vit.s
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gelatin coated tabs are ? evident and has ? size than equivalent capsule.
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are tamper evident...has smaller size
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What are enteric coated tabs intended to do?
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to pass thru the stomach intact to disintegrate and release their drug content for absorption along the intestinal...ie to dissolve at a pH > 4.8
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The coating system for an EC tab may be what?
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either aqueous or organic (nonaqueous)
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2 materials used in EC coated tabs?
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1. Shellac
2. cellulose acetate phthalate |
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Buccal and sublingual tabs have no what?
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no first pass effect (they go straight into circulation)(so all of the drug is absorbed
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What does the first pass effect refer to ?
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the fact that most oral tabs lose ~50% of their strength when they pass thru the liver
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Rate of absorption for buccal and sublingual tabs?
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rapid
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Why would buccal and sublingual tabs be desirable for rapid absorption?
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they are dissolved in areas having good blood supply (under the tongue has many blood vessels)
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Ex. of a sublingual tab?
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nitroglycerin tabs
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Buccal and sublingual tabs have no?
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disintegrant
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Describe chewable tabs?
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have smooth and rapid disintegration when chewed or allowed to dissolve in the mouth. Have a good taste and texture.
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2 examples of chewable tabs?
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Antacids, Kids multivit.s
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Is chewing of chewable tabs reqd?
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no
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How much pressure is used when compressing chewable tabs?
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minimal (this is why they can dissolve in mouth)
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A chewable tab may contain up to 50% of what?
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mannitol
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Chewable tabs are good for what?
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large tabs or tabs for kids (often come in fruit flavors)
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An advantage of chewable tabs?
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admin. of lg tabs to children and elderly who have difficulty swallowing
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How are effervescent tabs prepared?
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by compressing granular effervescent salts that release gas when in contact with water
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What important ingredients are in effervescent tabs?
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sodium bicarbonate and the organic acids (tartaric acid and citric acid)
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What does tartaric acid do for effervescent tabs?
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produces fragile granules
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What does citric acid do for effervescent tabs?
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produces sticky granules
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What occurs when effervescent tabs are in the presence of water?
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the additives (sodium bicarb, tartaric acid, and citric acid) react, releasing carbon dioxide that acts as a disintegrator and produces effervescence
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What is the advantage of the effect of effervescence?
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(from the CO2) kind of numbs the tongue and masks the taste
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Molded tabs are prepared on what? What are they intended for?
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a small lab scale...made in a mold and intended for rapid dissolution upon administration
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Molded tablets basic ingredients?
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drug + base
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The Base in molded tablets is usually what?
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lactose + sucrose 5-20%
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When preparing molded tabs the powder mixture is wetted with what?
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wetted with a 50% mixture of water and alcohol sufficient only to dampen the powder to be compacted
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hardness of a molded tab?
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molded tabs are soft
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Describe vaginal tabs?
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1. uncoated, bullet or ovoid shaped tabs
2. for local effect 3. shaped to fit snugly on plastic inserter 4. typically antibacterial for vaginitis |
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What does RDT stand for?
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rapid dissolving tab
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How quickly does an RDT dissolve?
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dissolves in the mouth 10sec -1min
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3 Adv.s of RDTs?
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1. quick onset of action with some drugs
2. easy for kids and elderly 3. administration easier than oral liquid |
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5 disadv.s of RDTs?
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1. difficulty in drug loading
2. taste masking is difficult because there are not a lot of additives 3. manufacturing cost 4. stability of products 5. friability |
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What does friability refer to?
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how easily a tab can break
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Name the 2 preparation techniques for RDTs?
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1. lyophized (freeze-drying)
2. compression |
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Describe the technique of lyophized (freeze drying) RDTs?
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tabs are prepped by foaming a mix of gelatin, sugar, drug, and other ingredients and pouring the foam into a mold
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How is a lyophized RDT like a tab?
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fragile porous
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How is a lyophized RDT packaged?
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in a blister pack
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How quickly does a lyophized RDT disintegrate?
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within seconds
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2 examples of lyophized RDTs using Zydis technology?
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1. loratadine (claritin reditabs)
2. zofran ODT |
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What kind of technology does the prep of RDTs by compression use?
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standard tableting technology
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Which is more fragile, Lyophized RDTs or Compressed RDTs?
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lyophized
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Which takes longer to dissolve
Lyophized RDTs or Compressed RDTs? |
compressed...take a few seconds longer
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The method of compression for RDTs makes use of what?
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superdisintegrants
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Compressed RDTs frequently include what excipients?
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effervescent excipients
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Compressed tabs are thinner than regular tabs for what reason?
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to provide a lg surface area
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Ex. of a compressed tab prepped by OraSolv and DuraSolv technology?
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Alavert
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7 aspects of a dosage form that may be tested?
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1. wt. variation
2. content uniformity 3. tablet thickness 4. hardness 5. friability 6. tablet disintegration 7. dissolution testing |
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Wt. variation in dosage testing refers to what?
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wt of each tab
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content uniformity in dosage form testing refers to what?
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amount of active ingredient in each tab...each tab must fall within range of 85%-115% of label claims...RSD < 6%
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4 things that determine the thickness of a tablet?
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1. the diameter of the die
2. the amount of fill permitted to enter the die 3. the compaction forces (micrometers) 4. the force or pressure applied during compression |
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Hardness in dosage form testing refers to what?
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the force needed to break the tablet...affects dissolution
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What is a friability test?
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wt. lost on exposure to slow rotation, weighed before and after...resistance to wt loss is an indicator of tabs ability to withstand abrasion in handling, packaging, and shipment.
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What is used to conduct a friability test?
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a friabilator
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What is the accepted wt. loss for a tab in a friability test?
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< 1%
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How is tablet disintegration tested?
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in a machine that simulates gastric fluid and mimics body temp of 37 degrees celsius...10 tabs are tested
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How long should an uncoated tab take to disintegrate when tested?
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30 minutes
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How long should a sublingual tab take to disintegrate when tested?
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2 minutes
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What does SGF stand for?
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simulated gastric fluid
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What is dissolution testing?
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making sure drugs dissolve in fluids...involves a paddle or basket
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What is the importance of dissolution testing?
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product optimization...QA in production...BIOEQUIVALENCE INDICATION (for generics to a brand name)...FDA reqt for marketing
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Temp. at which a dissolution test takes place and the amount of fluid involved?
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37 degrees celsius, 900 mL
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6 factors effecting disintegration and dissolution?
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1. particle size
2. hygroscopicity 3. type and conc. of disintegrant 4. binder and lubricant 5. manufacturing method 6. compression force |
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How is particle size related to disintegration and dissolution?
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a decreased part. size = increased disintegration
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What does hygroscopicity refer to?
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ability to absorb water
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An example of a lubricant?
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magnesium stearate
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How is compression force related to disintegration and dissolution?
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increased force = harder = decreased disintegration
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What are granules?
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prepared agglomerates of smaller particles of powder
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In what size range do granules fall?
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4-12 sieve size range
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How do granules flow compared to powder?
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well (think of granulated white sugar vs. powdered)
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Why are granules commonly used in tableting?
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to facilitate flow of material from hopper (feeding container) into tablet press
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Granules are more stable than powders when it comes to what?
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to atmospheric effects of humidity due to smaller surface area...eg, oral antibiotics for reconstitution
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What are easier to wet, granules or powders?
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granules
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The 2 methods of granulation?
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1. wet granulation
2. dry granulation |
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Why granulation?
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an important reqt in tablet manufacturing is that the drug mix should flow freely from the hopper of the tablet press into the dies to enable high speed compression of the powder mix
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7 steps of wet granulation?
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(widely used method)
1. weighing and blending ing.s 2. prep damp mass 3. screening into pellets or granules 4. drying the granules 5. sizing the granulation by dry screening 6. adding lubricant and blending 7. compressing tabs |
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In dry granulation what is done to the powder mix?
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is is compacted in large pieces and subsequently broken down into granules
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In dry granulation either the active ingredient or the diluent must have what?
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cohesive properties
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When is dry granulation used?
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when wet granulation is not possible due to moisture sensitivity or heat sensitivity
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6 steps of dry granulation?
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1. weighing the ing. mix
2. slugging or compressing into flat tabs or pellets 1 inch diameter 3. slugs are broken up by hand or mill 4. passed thru screen 5. lubricant is added 6. tab is compressed |
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When would direct compression be used?
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in some meds (KCl) that have cohesive and free flowing properties
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When using direct compression excipients with cohesive properties should be used for what reason?
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to allow tabs to be compressed withoout granulation
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When using direct compression what is the filler?
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spray dried lactose, microcrystalline cellulose
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What is the disintegrant in direct compression?
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direct compression starch cross linked CMC, cross linked PVP
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Some problems in tab manufacturing?
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capping/lamination...splittig of the tabs or layering...related to air entrapment in the tablet especially during COMPRESSION (causes tab to be friable)
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4 contributors to problems in tab manufacturing?
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1. air
2. high speed production (don't have enough time for bonding) 3. non-clean, or non-smooth punches (like if you don't use enough glidant) 4. granules with great portion fines (like powdered sugar) |
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What are capsules?
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a solid dosage form in which meds or inert substances are enclosed in hard or soft gelatin caps
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How are caps taken?
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usually intact but may be opened and mixed with liquid or food under a pharm.s supervision
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What dosage is used during clinical trials?
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capsules
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Two types of capsules?
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1. hard gelatin
2. soft gelatin |
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Hard gelatin caps consist of what?
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cap and body : cap slides over base
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What is an empty hard gelatin cap shell made out of?
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gelatin, water, sugar, dye, titanium dioxide
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Percentage of moisture in hard gel cap shell?
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13-16% moisture
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How should hard gelatin caps be stored?
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at cond's of intermediate humidity
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What could occur if a hard gelatin cap is stored at high humidity?
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dissolution time may increase
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Where do hard gelatin caps dissolve and expose their contents?
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dissolve in HOT water and in warm gastric fluid, and exposes its content in GIT
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Why does gelatin get digested in GIT?
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because it is a protein
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4 different capsule shapes?
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1. Coni-snap cap
2. pulvules 3. spansules 4. kapseal |
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Describe a Coni-snap capsule?
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has grooves to lock the body and the cap and a curved rim to prevent denting and splitting problems that are common with straight rims
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Describe shape of pulvule caps?
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one end tapered
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Describe shape of spansule caps?
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sharp pointed ends
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Describe shape of kapseal caps?
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colored band surrounds the joint b/n cap and body
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Describe cap size?
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human size ranges from 5 to 000 with 5 being the smallest and 000 being the largest
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How much powder can a cap accomodate?
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65 mg to 1g of powder (depends on the wt and density)
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What size cap should you use when making a drug?
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the smallest size that will hold your content
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The composition of caps is similar to what?
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tabs
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2 general things caps are composed of?
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1. active drug
2. excipients |
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Describe 4 possible excipients of capsules?
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1. diluent (may be added...such as lactose or microcrystalline cellulose)
2. disintegrant (like starch, sometimes added to enhance the powder break up and spreading after shell opening in stomach 3. Glidant and/or lubricant (silicon dioxide or mg stearate) 4. surfactant (Na lauryl sulfate...to facilitate wetting of the cap content by the GI fluid |
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For uniform drug distribution in caps you would use what?
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similar density excipients if possible and particle reduction
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3 methods of cap filling?
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1. the punch method
2. hand operating machines fill 3. on large scale |
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3 methods of cap sealing?
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1. sometimes colored band of gelatin used
2. heat welded 3. liquid and low heating |
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Once finished a cap is often covered in powder, how is it cleaned?
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vacuum, individually
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What is a soft gelatin cap shell made of?
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1. gelatin
2. polydydric alc. as sorbitol or glycerin to make it more elastic 3. water...higher percentage than hard shell 4. preservative (because it has a larger percentage of water) (like methylparaben) 5. only commercially prepared |
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3 things soft gel caps can be filled with?
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1. liquid, pastry and dry fills
2. solids (in solution, suspension,dry powder, pellets, small tabs) 3. liquid (water immiscible volatile and nonvolative oils, water miscible non-volatile liquids like PEG) |
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What liquids cannot be filled in soft caps?
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liquids with water >5%, or low MW volatile organic compound as alcohol
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How do you test for disintegration of capsules?
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capsule in basket at 37% C...capsule has to disint. to soft mass
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How do you test for dissoluton of caps?
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capsule may be tested intact or emptied if gelatin interferes with test
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How do you test for dosage form unity of caps?
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wt variation and/or content uniformity
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How does wt variation of hard gel caps test for dosage form uniformity?
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10 caps are indiv. weighed INTACT and the EMPTIED SHELLS to determine the content
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How does wt variation of soft gels test for dosage form uniformity?
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INTACT and EMPTIED caps after washing
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What is content uniformity?
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determination of the active ingredient content in the cap
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Unless otherwise indicated within what range should the ACTIVE INGREDIENT AND THE WT VARIATION fall within for the first 10 caps tested?
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85-115%
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How is the stability of a cap tested?
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stab. of the active ing. and well as the effect of temp, humidity, and light on the cap...exposed to accelerated stability studies
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How are caps orally administered?
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with water...if need to be opened it should be done under a pharmacist's supervision
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Capsule's relevance to food is what?
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very important whether to take with or without food
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