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37 Cards in this Set
- Front
- Back
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Types of tablets (1)
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Compressed
Multiply Compressed Sugar-coated Film-coated (most common) Gelatin-Coated Enteric-Coated Molded |
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Types of tablets (2)
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Triturates
Hypodermic Dispensing Immediate-Release Instantly Disintegrating or Dissolving Extended-Release Vaginal Tablets |
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Compressed Tablets
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Solid dosage forms prepared with suitable excipients and tablet machines capable of exerting great pressure in compacting the powdered or granulated material
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Usual Tablet Excipients
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Diluents or fillers
Binders or adhesives Disintegrants Antiadherents Lubricants Glidants Colorants, flavorants |
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Tablet diluents and fillers
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Add the necessary bulk to a formulation to prepare tablets of the desired size
Dibasic calcium phosphate Not used too much (hard on instrumentation) Lactose Readily available and cheap Mannitol Microcrystalline cellulose Powdered cellulose Starch |
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Tablet Binders or adhesives
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Promote adhesion of the particles
Acacia: not used frequently Alginic acid Carboxymethylcellulose Gelatin Liquid glucose Methylcellulose Povidone Pregelatinized starch |
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Disintegrants
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Promote breakup of tablets after administration to smaller pieces for ready drug availability (in body)
Microcrystalline cellulose Sodium starch glycolate Starch |
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Glidants
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Improve powder flow
Colloidal silica light and fluffy difficult to handle, really helps improve flow as glidant especially in tablets Cornstarch Talc |
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Lubricants
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Reduce friction during tablet compression (don’t want sticking)
Calcium stearate Magnesium stearate (main one) Stearic acid Zinc stearate |
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Antiadherents
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Prevent tablet ingredients from sticking to punches and dies during production
Work in conjunction with lubricant to prevent sticking Talc (also a glidant) Magnesium stearate (also a lubricant) |
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Three Main Methods for the Preparation of Compressed Tablets
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Wet Granulation
Dry Granulation Direct Compression From most complicated to least |
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Wet Granulation
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Components mixed with granulating fluid (+ binder), dried and milled to produce granules with good flow and compression properties
Good flow necessary for high speed presses Produces robust formulations Can also be used to distribute low concentrations of drug to achieve acceptable content uniformity |
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Steps in Wet Granulation Process
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Powders dry blended
Blended material wetted with a binder solution Wet milling (optional) Granulation dried Dried granulation milled to correct particle size Granules blended with remaining excipients Tablet blend compressed |
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Key Variables For Wet Granulation Processes
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Amount of Binder
Increase binder, increased granule density Method of Binder Addition Fine spray applied uniformly over moving bed to avoid over-wetting areas Granulating (Wet Massing) Time Increase time, increases granule density If too much, paste formation could result |
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Steps involved in DRY GRANULATION process
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Milling and mixing of active ingredient and excipients
Compression into slugs or roll compaction Milling and screening of slugs and compacted powder Mixing with lubricant and disintegrant Compression |
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Steps involved in DIRECT COMPRESSION
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Milling and mixing of active ingredient and excipients
Compression Easiest and least complicated method |
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Drying
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Tray
Old technology, but still used Fluid Bed (most common) Warm Air passed through the fluidized bed Particle size is controlled this way (1 step process) Vacuum Could be gas assisted Microwave Also involves convection and vacuum drying |
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Milling
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Screen size
Primary factor that determines particle size Impeller speed Increasing speed could decrease particle size Impeller shape/design Affects angle of nip (angle at which particle leaves sieve) Hammers/knives forward Feed rate |
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Powder Mixing
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Perfect Homogeneity
Every sample will have exactly the same composition as all other samples taken from the blend Random Mixing State at which the probability of finding a particle of a given component is the same at all points in the mixture Ordered Mixing Physically adsorb drug uniformly onto excipient to reduce segregation |
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Precompression Force
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Small amount of force applied to material to remove entrapped air, forming a loose compact
Decreases the chance of lamination and capping Weight adjustment often performed at precompression stage by measuring punch displacement |
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Main Compression Force
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Larger amount of force applied to material, bonding particles together to form the tablet
Compression profiles -performed to determine the effect of increasing force on the physical properties of the tablets Over-Compression - excessive (too much) force applied resulting in reduced hardness, lamination and capping |
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As Compression Force, increases...
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Thickness decreases
Hardness initially increases, but can then decrease Friability initially decreases, but can then increase Disintegration time increases Dissolution rate decreases Tablet density increases |
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Tablet Press Speed
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The time that the die is under the feedframe varies with press speed
Affects die fill Increase feeder paddle speed or fill depth as press speed increases Press speed affects dwell time Duration that the force is applied to material Short dwell times lead to capping/lamination |
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As Tablet Press Speed Increases....
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Weight variability may increase (especially for poor flowing blends)
Dwell time decreases, which could exacerbate lamination and capping Results in decreased hardness and increased friability (breaking) |
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In-Process Controls for Tablets
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Appearance
Weight (mean and individual) Thickness Hardness Friability Disintegration Dissolution |
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Tablet Weight and USP Weight Variation Tests
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Weigh 10 uncoated tablets individually and calculate an average weight
Ranges 90%-100% The tablets are assayed and the contents of active ingredient in each of the 10 tablets is calculated |
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Content Uniformity
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USP method –10 units are individually assayed for their content
Make sure within range, 70%-110% |
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Tablet Thickness
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Thickness of 5-10 tablets measured using a thickness gauge at defined intervals throughout the run
Indicative of tablet hardness and weight Thin tablets: May imply hard or light tablets Thick tablets: May imply soft or heavy tablets Specification should be based on the desired tablet hardness and disintegration times (specific is set by preparer not USP) Important specification for packaging operation |
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Hardness
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Hardness of 5-10 tablets measured using a hardness tester throughout compression run
Increased variability in hardness may imply weight variability or variable punch length As hardness increases, Disintegration time increases Dissolution decreases Friability decreases, then may increase Decreasing press speed can increase hardness |
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Friability
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Indicator of how well tablets will hold up during coating, packaging, or shipping
Typically, 6 g of tablets (or at least 20 tablets) weighed to 3 decimal places. Tablets put in friabilator and tumbled for 4 minutes at 25 RPM Tablets removed from friabilator, dedusted and reweighed % weight loss calculated; limit usually 0.3- 0.5% |
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Tablet Disintegration
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Should be performed on uncoated tablets
Coating can bias the results Not performed for chewable or modified release tablets Indicator of potential dissolution problems Release test for some old products These products usually lack dissolution tests |
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Disintegration Test Steps
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6 tablets put in disintegration basket
Media usually 0.1 N HCl or Water at 37 deg C +/- 2 deg C 10 mesh screen on bottom of tubes Basket raised and lowered 32 cycles/min Time all particles pass through the screen recorded at certain amount of time Discs may be used for tablets that float |
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Dissolution Considerations
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Does an in-vivo/in-vitro correlation exist?
How do formulation and processing changes, as well as scale-up affect the dissolution profiles? FDA policy to have dissolution profiles generated in water, 0.1 N HCl, USP buffer media at pH 4.5, 6.5 and 7.5 |
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Processing Factors That Can Affect Dissolution
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Milling Conditions
Drug substance and granulation Granulation Process Amount of binder, wet massing time, shear Lubrication Time Compression Parameters Compression forces and press speed |
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Compression Coating
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Compress a tablet within a tablet
Inner core placed in a die containing half the coating material Remainder of coating material filled into die and tablet compressed Can minimize contact area between two incompatible drugs Can encase toxic drugs in an inert outer coat |
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Layered Tablets
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A second or third layer of material is compressed onto the original core
Could minimize contact area between incompatible materials Provides a unique market image |
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Coating
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Applying a thin layer of polymer (film coat)
Use coat to give desired properties Science used in foods carries into pharmaceuticals (sugar coating) |
