Tablets Flashcards
What are tablets?
Tablets are solid dosage forms and are prepared by compression (80-90%) and moulding (10-20%). Tablets also contain one or more medicinal substances in addition to diluent
What are some basic components of a tablet?
Drug
Diluent
Disintegrants
Binders
Colourants
Coatings
How are compressed tablets formed?
These tablets are prepared with machines capable of exerting great pressure in compacting the powdered or granulated material.
Compressed tablets are the most basic type of tablets in terms of functionality
Are all powders good candidates for compression into tablets?
No, some powders may have poor flow and compression characteristics. They require tremendous pressure and the resulting tablet may lack in desired physical qualities
These powders can be modified in a way that allows for better compression
What is granulation?
The process of particle size enlargement of powdered ingredients (agglomeration)
Common methods of granulation:
Wet granulation
Dry granulation
Describe the process of dry granulation
The powder blend is squeezed through a set of rollers. This turns the powder into flakes, a form that is further milled and sized into larger granules.
Describe the process of wet granulation
Dry powder is placed into a machine called the granulation and it is mixed with other ingredients like binder, water (need some type of liquid to act as the granulating fluid).
This results in the formation of a paste and is known as the wet granular mass.
The paste is dried and results in the dry granular mass. This mass can be broken into dry granules
What is the utility of binders in tablets?
Binders are a critical component because the increase durability, a quality especially important during shipping.
Binders impart cohesiveness to powders, therefore providing the necessary bonding to form granules, which are then compacted into tablets
Too little binder=fragile tablets
Too much binder = excessive hardness (slow disintegration)
Ex. Starch, gelatin, sugars, etc
Do excipients in drugs have more than one purpose?
Yes, many tablet excipients may perform more than one function
Ex. Starch has binding and disintegration properties while also adding to the softness
What is the purpose of lubricants in tablets?
- Provide glidant effect by coating and lubricating particle surfaces —> improves flow properties of tablet granulation
- Provide anti-adhesive effects —> prevents adhesion of materials to punches and fixes during tablet compression
- Act as a lubricant between walls of die cavity and tablet —> facilitating tablet ejection
What are the two main types of lubricant?
Water insoluble:
Magnesium stearate
Calcium
Stearic acid
Talcum
Hydrogenated vegetable oils
Water soluble:
Sodium stearate
Polyethylene glycol
Sodium benzoate
What percentage of a tablet is comprised of lubricants?
Less than 1%
Lubricants are usually the last item to be added
What are some disintegrants used in tablets?
Starch
Cellulose
Clays (bentonite)
Gums (acacia)
Why do effervescent tablets fizz when exposed to water?
They contain sodium bicarbonate and citric acid. When these two are exposed to water, CO2 is released
What is the purpose of colouring agents in tablets?
To enhance aesthetic quality
Product identification
Can drug manufacturers choose any colourant for tablets?
No, colourants must be approved by regulatory bodies and are subject to rigid toxicity standards
Ex. FD&C Red No. 3
What types of tablets need flavouring agents?
Sweeteners and flavouring agents are required for chewable and effervescent tablets.
They are not required for standard compressed tablets, which are intended to be swallowed
What are molded tablets?
They make soft, easily disintegrating tablets. They are designed for rapid dissolution
Are all excipients compatible with other tablet ingredients?
Unfortunately not all excipients are compatible.
Avoid combining calcium salts with tetracycline (interferes with absorption)
Bentonite and kaolin are highly adsorbent, which could inactivate certain drugs
Are tablets the most popular and frequently used dosage form?
Yes, largely due to its ease and economy of preparation, packaging and shipping, accuracy of doses stability, and patient acceptability
What is the purpose of tablet coatings?
Smooth surface (product quality)
Product identification
Mask drug taste
Improve drug stability
What are the two functional tablet coatings?
Enteric-coating (EC)
Controlled/sustained release
Why do some tablets have a line down the middle?
These tablets are designed to be easily split.
What are the different types of tablet coatings?
Sugar coating
Film coating
Functional coating
What are some problems with sugar coating on tablets?
Many steps of this process involve tumbling - tablets must be hard enough to withstand it
Sugar coating pans must mix uniformly or coating goes on unevenly resulting in tablets of different sizes and weights
What is the most common type of tablet coating?
Film coating is the most common
What is film coating in relation to tablets?
It is a thin coating of a plastic-like material over the compressed tablets
Ex. HPMC (hydroxy propyl methyl cellulose)
What is the process of applying a film coating?
Tablets move through a zone where the coating material is applied
The three ways a film coating can be applied:
Coating pan
Spray in a fluidized stream
Press coating
What is pan coating?
Pan shape, rotational speed, and loading effect the mixing of tablets and coating
Uniform mixing is essential to deposit the same quantity of film on each tablet
What are some issues with pan coating?
Poor tablet movement in the coating pan may cause unacceptable colour uniformity or affect the integrity of enteric film
Ensure equipment is able to mix given tablet shape without chipping or breaking tablets
What is fluidized bed coating?
It involves throwing tablets in a chamber via air flow while spraying the coating while tablets are in the air. This allows for the coating to dry much faster
What is compression coating?
It is the compaction of a dry coat around a tablet core. It can be produced on the same tableting machine.
This type of coating avoids the use of solvents (no time needed for drying), but the machinery involved is complex so it is not used commonly
What is the difference between the aqueous and organic film coating process?
Organic process is expensive and sometimes not environmentally friendly, so aqueous is preferred, but it also presents its own challenges
Water slowly evaporates compared to organic solvents
Water is really cohesive, so the aqueous coating is applied roughly on the tablet
The core tablet can be disfigured if subjected to aqueous coating solutions for too long
What is enteric coating?
Allows for disintegration in the intestine rather than the stomach
Ex. Cellulose acetate phthalate is the most common material used in enteric coating
Enteric coatings do not dissolve in the acidic pH of the stomach (protects drug from acid hydrolysis)
How do timed release tablets work?
These tablets can have many layers of coating with varying thickness. The coatings are broken down differently depending on composition and thickness, allowing for timed release
What are some physical features of tablets that are evaluated?
General appearance: texture, scoring, and engraving
Size: diameter and thickness
Shape: oval, oblong, triangular & flat vs. Varying degrees of convexity
Organoleptic properties: colour, odour, and taste
Other:
Tablet weight, thickness, hardness, disintegration, content uniformity, and drug dissolution
How is tablet hardness measured?
It is defined as the force required to break a tablet in a diametric compression test
Oral tablets: 4-8kg
Chewable tablets: 3kg
Modified release tablets: 10-20kg
Tablets should be sufficiently hard to resist breaking or chipping during packaging, shipping and normal handling, yet soft enough to disintegrate or dissolve properly after administration
What is friability in relation to tablets?
Ability of tablet to withstand abrasion in packaging, shipping, and handling (tendency to crumble)
Usually loosing less than 1% of mass to crumbs and chips following subjection to a tumbling apparatus is considered acceptable
How can drug content uniformity be calculated?
Weight variation:
Relies on tablet weight to assess the amount of drug in each unit. The greater the amount, the more accurate.
Content uniformity:
May be applied in all cases
Assess uniformity of content by assaying each dosage unit
What is the most important test of a tablet?
Dissolution testing because absorption and bioavailability are dependent upon the drug being in the dissolved state.
Useful in the early stages of drug development and formulation to optimize the dosage form characteristics (don’t need human trials initially, lost lower cost and risk to human subjects)
What are molded tablets?
They are prepared by moulding rather than by compression
The tablets are soft, soluble and are designed for rapid dissolution
They do not contain disintegrants, lubricants or coatings
DO NOT USE FOR POTENT DRUGS due to concerns about difficulties with content uniformity
What are some common diluent in molded tablets?
Lactose, mannitol, dextrose
What is a notable quality of chewable tablets?
They are designed to be disintegrated in the mouth (only have to do dissolution and absorption)
What are the advantages of chewable tablets?
Pleasant taste (o bitter or unpleasant aftertaste)
Convenient and high patient acceptance
Rapid onset of biological activity (no disintegration)
What is a common excipient in chewable tablets?
Mannitol
What are the advantages of mannitol as an excipient?
This excipient gives chewable tablets the following characteristics:
70% sweetness compared to sucrose (mask bitter taste)
Cool taste and mouth-feel (similar to menthol)
Non-hygroscopic (does not absorb moisture)
What excipient is used in chewable tablets that is sugar-free?
Xylitol is used in sugar-free chewable tablets
Is it okay to swallow chewable tablets?
No, the tablet is not designed to be disintegrated in the GI tract. Chew to break the tablet into smaller pieces
What are effervescent tablets?
They are wafer like tablets which dissolve rapidly in water
Tablet breakup is facilitated by the release of carbon dioxide generated from sodium bicarbonate and citric acid (acid+base=CO2 +water)
What are some special considerations for effervescent tablets?
BInders, fillers, and lubricants are water soluble
Moisture excluded during manufacturing
Tablets are individually wrapped to prevent them from merging
When should effervescent tablets be administered following dissolution into water?
Once the effervescence stops, wait 5 minutes and stir the solution for about 10 seconds and then drink
What are sublingual and buccal tablets?
Sublingual (under the tongue)
Buccal (between cheek and gum)
Sublingual tablets are designed to rapidly dissolve and cause an immediate systemic effect by absorbing via the oral mucosa
Buccal tablets on the other hand are designed to erode relatively slowly. Fentanyl can be administered via this dosage form
What are some shared properties of sublingual and buccal tablets?
These tablets are small, soft and flat (can be molded or compressed)
These tablets do not contain a disintegrant
What are orally disintegrating tablets?
A solid dosage form which disintegrates rapidly, usually within a matter of seconds, when placed upon the tongue (dissolve within 60 seconds without water)
Are ODTs always intended to produce a faster therapeutic onset?
That is a potential use case, but it can also circumvent problems such as difficulty in swallowing
What are some special instructions for ODT use?
Do not try to administer tablets with wet hands
Store tablets in a dry place
Some products may cause a burning or prickling sensation on the tongue
What are some challenges associated with sublingual, buccal, and ODT dosage forms?
They are only good for small doses
Need to be formed from fine grains to mask taste and improve palatability
Balance between friability and dissolution speed
Extra packaging = more expensive
What is the utility of lozenges as a dosage form?
Lozenges promote saliva flow, which is soothing
They contain one of more medications, usually in a flavoured, sweetened base
Useful for patients who have difficulty swallowing (paediatric, geriatric, GI blockage patients)
What are the two different types of making lozenges?
Pastilles (Moulding gelatin, sucrose, or sorbitol base)
Troches: (compression of sugar-based tablets)
What are the basic properties of a good lozenge?
Smooth surface texture
Slow uniform dissolution or erosion over 5-10 minute period
Pleasant flavour masking drug taste
What can compounded lozenges be made out from?
Sugars to form a hard lozenge
Polyethylene glycol (PEG) to form a soft lozenge
Gelatin to form a chewable lozenge
Describe the composition of hard lozenges?
They can be considered solid syrups of sugars
They usually contain 55-65% sucrose and about 45% corn syrup
The sugars are heated and other ingredients and poured into moulds
Can sugars be heated indefinitely without altering the qualities of the lozenge?
No, at a certain temperature depending on the exact composition, the sugars will caramelize.
Caramelized sugars have a decreased shelf life
Do hard lozenges contain a lot of water?
No, this dosage form needs a low moisture content (0.5-1.5%) so water is evaporated off by boiling the sugar mixture during the compounding processs
What is the general composition of soft lozenges?
Typically made of ingredients such as polyethylene glycol (PEG) 100 or 1450, chocolate, or a sugar-acacia base
What is the purpose of acacia gel?
Acacia is used to add texture and smoothness to the lozenge
What is the purpose of silica gel?
Silica gel is used as a suspending agent to keep materials from settling to the bottom of the mould
What temperatures do the ingredients that go in a soft lozenge have to endure during the heating process?
50*C, so ingredients like sweeteners (sodium saccharin) should be heat stable
Should troche moulds be under filled for the highest quality lozenge?
No, PEGs contract as they cool so the cavities of the troche mold should be overfilled
But if the base is chocolate, it doesn’t shrink therefore no need to overfill
What are some techniques that can improve the quality of lozenges produced in the pharmacy?
Be mindful of the base and how much it contracts once cooling, pour into moulds accordingly
Before the material fully solidifies, use a spatula to level and even out the poured mass
Once the material fully cools, apply heat for a short time (warm spatula, blow dryer) to give the surface a smooth finish
What is the composition of chewable lozenges?
Most formulations are based on the glycerinated gelatin suppository formula which consists of glycerin, gelatin, and water
How much flavouring agent needs to be added to chewable lozenges?
Make chewable lozenges without drug and add flavouring to level desired. This product is easy to taste testing
When making active chewable lozenges, start with 5-10x the amount of flavouring used in the inactive chewable lozenges
What is capping in relation to tablet processing problems?
The partial or complete separation of the top or bottom crowns of a tablet from the main body of the tablet
What is lamination in terms of tablet processing errors?
The separation of a tablet into two or more distinct layers, ie transverse cracking and separation of tablet
What causes capping and lamination?
Air entrapment in light and fluffy powders
Too little moisture in granulation
Weak granules or too weak a binder
Improper adjustment of machinery
What is picking in relation to tablet processing errors?
The surface material from a tablet that is sticking and being removed from the tablet surface by a punch.
Logos and letters are “engraved” into pills with this method
What is sticking in relation to tablet processing errors?
The tablet material adheres to the die wall
What causes picking and sticking?
Inadequate lubrication (adhesive components may be present)
Insufficiently dried wet granulation
Poor finish on punch surfaces
What is whiskering in relation to tablet processing errors?
Fine edges are attached to tablet but they do not get removed. These fine edges break during friability testing, causing high friability values
What is chipping and splitting in relation to tablet processing errors?
The tablet can get chipped or split in half. This usually occurs die to poor finish or worn punches and dies
What is friability?
It refers to the ability of the compressed tablet to withstand abrasion or crumbling in packaging, handling, and shipping
What causes friability?
Inadequate bonding of tablet mix
Too much or too little pressure
Worn punches or dies
What causes poor disintegration?
Tablet hardness too high
Low amount of disintegrant
Too much binder
Over lubrication causing “waterproofing”
What is mottling?
An unequal or uneven distribution of colour on or in a tablet
What causes mottling?
Uneven distribution of powdered lakes (a type of pigment)
Soluble dye migration during drying (dye moves towards droplets on surface of tablet during evaporation and are deposited)
What are the consequences of low hardness?
Low hardness can lead to a rapid release of drug from dosage form or a tablet will be too fragile for shipping and handling
What can cause low hardness?
Compression pressure too low
Binder can affect the hardness of a tablet
