Lecture 3 Tablets Flashcards
What distinguishes capsules from tablets?
Tablets are compressed powders.
What are the qualities of a good tablet?
Accurate and uniform of weight, homogeneity, absence of incompatibilities (ex. metal shards from machinery), stability and hardness, ease of disintegration, reasonable size and shape, pleasing appearance, ease of manufacturing, and economy of production.
What are the advantages of tablets?
Accurate dosage/minimum variability, absence of alcohol, concentration variability, elegance, patient acceptance, convenience (light and compact), tamper resistant, low cost, easiest/cheapest to package and ship, production identification is simple, ease of administration, special release profiles possible, suited for large-scale production, and best overall properties of all oral dosage forms.
What are some disadvantages of tablets?
Swallowing, difficult to extemporaneously prepare, some drugs resist compression, poorly wetting drugs, slow-dissolving drugs, intermediate to large dosages/bad odor, and oxygen/moisture-sensitive require coating.
What are the types of tablets are available?
compressed, multiply compressed, sugar-coated, film-coated, gelatin-coated, enteric-coated, buccal and sublingual, effervescent, instantly disintegrating or dissolving, and vaginal tablets.
What are compressed tablets?
Solid dosage forms prepared with suitable excipients and tablet machines capable of exerting great pressure in compacting the powdered or granulated material.
What are the usual tablet excipients?
Diluents or filler, binders or adhesives, disintegrants, antiadherents, lubricants, glidants, and colorants/flavorents(might not be used).
What is the purpose of a diluent?
To add the necessary bulk to a formulation to prepare tablets of the desired size.
What are some examples of diluents?
dibasic calcium phosphate, lactose, sucrose, mannitol, microcrystalline cellulose (also disintegrant), powdered cellulose, and starch.
What is the purpose of a binder or adhesive?
To promote adhesion of the particles.
What are some examples of binders or adhesives?
Acacia, alginic acid, carboxymethylcellulose, gelatin, liquid glucose, methylcellulose, povidone, pregelantinized starch.
What is the purpose of a disintegrant?
To promote breakup of tablets after administration to smaller pieces for ready drug availability.
What are some examples of disintegrants>
microcrystalline cellulose (also diluent), sodium starch glycolate, and starch.
What is the purpose of a glidant?
To improve powder flow.
What are some examples of glidants?
Colloidal silica, cornstarch, and talc.
What is the purpose of a lubricant?
Reduce friction to punch/die during tablet compression and facilitate tablet ejection, improve powder flow properties, decrease adhesion to punch/die, and reduce punch/die wear.
What are some examples of lubricant?
Calcium stearate, magnesium stearate, stearic acid, and zinc stearate (waxy material).
When would you add a lubricant in the mixing process?
At the end because it won’t dissolve if it is blended throughout.
What is the purpose of an antiadherent?
It prevents tablet ingredients from sticking to punches and dies during production.
What are some examples of antiadherent?
Talc and magnesium stearate
Which excipient was most likely added to a tablet formulation with the sole purpose of facilitating powder flow?A. Magnesium stearateB. Microcrystalline celluloseC. Collidal silicaD. Starch
C. Collidal silica
There is a problem with the dissolution of a drug product. What are possible reasons for this and what recommendation do you have to rectify the problem?
Adding the lubricant too early in the production process or not adding enough disintegrant. Add a disintegrant such as starch or add lubricant at the end of production process.
List 5 ways a patient might misuses a tablet dosage form and suggest counseling strategies to dissuade them from doing so.
They could crush/chew the tablet, break the tablet, take with or without food, with alcohol, more or less than prescribed, time of day, route of administration, storage. Make sure they are aware of the proper dosage to take and let them know the side effects of not taking it correctly.
What type of excipient is Collodial Silicone Dioxide and what does it do?
A glidant that helps the powder to flow.
What type of excipient is microcrystalline cellulose and what does it do?
A disintegrant that helps facilitate the break up and distribution once in the body. A diluent that is used to add bulk.
What type of excipient is stearic acid and what does it do?
A lubricant that reduces friction to punch/dye, helps tablet ejection, and improves powder flow.
What are the three ways to prepare compressed tablets?
Wet granulation, dry granulation, and direct compression.
What are the benefits of preparing by wet granulation?
Produces granules with good flow and compression properties (good flow is necessary for high speed presses), produces robust formulations, can be used to distribute low concentrations of drug to achieve acceptable content uniformity.
What are the steps of the wet granulation process?
- Powders dry blended2. Blended material wetted with a binder solution3. Wet milling (optional)4. Granulation dried5. Dried granulation milled to size6. Granules blended with remaining excipients7. Tablet blend compressed
What happens if you increase the amount of binder in the wet granulation process?
Increasing binder will increase granule density
How should you add a binder in the wet granulation process?
Finely spray uniformly over a moving bed to avoid over-wetting areas.
What happens if you change the time of granulating in the wet granulation process?
Increasing the time increases granule density. If too much, paste formation could result.
What are the steps of the dry granulation process?
- Milling and mixing of active ingredient and excipients2. Compression into slugs or roll compaction3. Milling and screening of slugs and compacted powder4. Mixing with lubricant and disintegrant5. Compression
What are the steps of the direct compression process?
- Milling and mixing of active ingredient and excipients2. Compression
Why can’t every drug be direct compressed?
Because a material that doesn’t have good flow or good compressibility need to be made into granules first.
Why would you chose Dry over Wet granulation?
Drugs that are moisture sensitive can not be processed with wet granulation.
What is important in the blending process?
Addition of lubricant should be at the end of the blending operation. It is important to determine the appropriate blending time - don’t want to over mix (causes separation).
What are the three ways of drying?
Tray (may be used for sensitive materials), Fluid Bed (Warm air is passed through the fluidized bed), Vaccum (could be gas assisted)
What is the primary factor deterimining particle size in milling?
Screen size
Increasing the speed of the impeller in milling would cause particle size to increase or decrease?
decrease particle size
How does the shape of the impeller in milling affect particle size?
The angle of nip(how the blade hits the screen) and if the hammer/knives are forward.
What is the precompression force?
A small amount of force applied to material to remove entrapped air, forming a loose compact. It decreases the chance of lamination and capping. Weight adjustment is often preformed at precompression stage by measuring punch displacement.
What is the main compression force?
It is a larger amount of force applied to material, bonding particles together to form the tablet.
Why is a compression profile preformed on tablets?
To determine the effect of increasing force on the physical properties of the tablets.
What effect will over-compression of tablets incur?
Excessive force applied results in reduced hardness, lamination and capping.
As compression force increases…Thickness?Hardness?Friability(easily broken)?Disintegration time?Dissolution rate?Tablet density?
When compression increases….Thickness decreaseshardness increasesfriability decreasesdisintegration time increasesdissolution rate decreasestablet density increases
The time that the die is under the feedframe does not vary with press speed. T/F
False, press speed affects die fill. Increased feeder paddle speed or fill depth as press speed increases.
Increased tablet press speed decreases dwell time which can exacerbate lamination and capping. T/F
True, increased tablet press speed results in decreased hardness and increased friability.
What are the in process controls for tablets?
Appearance, weight(mean and individual), thickness, hardness, friability, disintegration, dissolution.
What is the USP method for content uniformity?
10 units are individually assayed for their content. Has to be between 85% and 115% of the label calim and the RSD less than 6 percent.
What does tablet thickness tell you about the tablet hardness and weight?
Thin tablets may imply hard or light tablets. Thick tablets may imply soft or heavy tablets.
As hardness increases…Disintegration time?Dissolution rate?Friability?
As hardness increases…Disintegration time increasesDissolution rate decreasesFriability decreases
How is friability measured?
6g of tablets (or at least 20 tablets) are weighed to 3 decial places. Tablets are put in friabilator and tumbled for 4 minutes at 25 rpm. Then they are dedusted and weighed. Percentage of weight loss is calculated: limit usually 0.3% to 0.5%.
To test a tablet for disintegration you would perform it on?
uncoated tablets in water, Enteric-coated tablets tested in simulated gastric fluid, not performed on chewable or modified release tablets.
What is the USP Disintegration Test?
6 tablets put in disintegration basket, media usually 0.1 N HCL or water at 37 C, 10 mesh screen on bottom of tubes, basket raised and lowered 32 cycles/min, discs may be used for tablets that float.
What types of tablet coating are there?
sugar coating(old school), film coating (most tablets), enteric coating, and fluid bed coating
Steps of sugar coating?
waterproofing and sealing, subcoating, smoothing and final rounding, finishing and coloring, and polishing.
Steps of film coating?
Places a thin-like material over the compressed tablet.
What is the purpose of enteric coating?
Intended to pass intact through the stomach to disintegrate and release drug content for absorption along the intestines.
What is fluid bed coating?
Spray coating of powders, granules, beads, pellets, or tablets suspended by a column of air.
What is compression coating?
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.
What is the benefits of compression coating?
Can minimize contact area between two incompatible drugs, can encase moisture sensitive substances.
What are the benefits of layered tablets?
Could minimize contact between incompatible materials, provides a unique market image.
What tests are not USP to test tablets?
Thickness and Hardness
Roller compaction is involved in the process of…A. determining the particle size distribution of a sampleB. applying enteric coating to compressed tabletsC. stabilizing hard gelatin capsulesD. preparing compressed tablets by the dry granulation method
D. preparing compressed tablets by the dry granulation method
Which method of tablet manufacture requires the fewest processing steps?A. dry granulationB. direct compressionC. wet granulation
B. direct compression
One advantage of tablets is that they are readily prepared extemporaneously. T/F
False
When considering compression profiles, one would expect _______________________ in tablet disintegration time as a result of increased compression force.A. no changeB. increaseC. decrease
B. increase
An excipient added to a tablet formulation to improve flow properties is aA. disintegrantB. glidantC. binderD. diluent
B. glidant
What tests are USP to test tablets?
Tablet Weight, Content Uniformity, Friability, Tablet Disintegration, and Dissolution
Some old tablets do not have dissolution profiles because they were grandfathered in. T/F
True
How is dissolution testing preformed?
Dissolution media placed in vessel and allowed to come to 37 and 0.5 Celsius. Stirrer is rotated at specified speed and samples of the media are withdrawn and analyzed at stated intervals.
What are the different dissolution profiles and what do they mean?
I - High solubility and high permeability (good)II - Low solubility and high permeability (ok)III - High solubility and low permeability (ok)IV - Low solubility and low permeability (bad)
What processing factors can affect dissolution?
Milling conditionsGranulation processLubrication timeCompression parameters
