Tablets 1
In what areas of tablet knowledge should a pharmacist be educated on, in order to answer patient questions?(5)
- Onset of action - Conversion to other dosage forms - Side effects - Degradation/expiry - Counterfeiting risks
In what ways may tablets vary from each other? (6)
- Size - Shape - Weight - Hardness - Thickness - Disintegration characteristics ** All are dependent on the intended use of the tablets and their method of manufacturing
Name 2 water soluble lubricants:
- Sodium stearate - PEG's
What are the advantages of tablets as a dosage form? (5)
- Stability - Taste masking - Convenience - Dosing accuracy - Cheaper to manufacture
List examples of some common binders: (4)
- Starch - Gelatin - Glucose - Polyvinylpyrrolidone (povidone, PVP)
Provide some examples of binder solutions: (3)
- Starch paste (10%) - Gelatin solution (10-20%) - Glucose solution (25-30%)
What types of tablets are compressed tablets the "basis" for?
- Sugar coated - Film coated - Enteric coated - Multi-layered - Sustained release - Controlled release - Tablets for solution - Effervescent tablets - Lozenges - Compressed inserts - Buccal and sublingual tablets - Compressed inserts (vaginal)
What type of sweeteners are used in tablet formulation?
- Sugar diluents are used (such as lactose) - Artificial agents are widely used, as well as confectioner's sugar
What is a binder?
- They impart cohesiveness to powders, therefore providing the necessary bonding to form granules, which are then compacted into tablets. - Often considered the "most critical ingredient"
What are the 2 types of lubricants?
- Water insoluble - Water soluble
What are the 3 commonly used processing methods of powders?
- Wet granulation - Dry granulation - Direct compression
Provide examples of when an excipient would not be compatible with the rest of the formulation:
1. Calcium salts with tetracycline - forms a complex, which interferes with absorption of tetracycline in the gut (avoid calcium -- phosphate, -- sulcate and -- carbonate) 2. Bentonite and kaolin are high adsorbent - therefore they may adsorb and inactivate certain drugs - use w/ caution
What are the two major groups that tablets can be divided into?
1. Compressed (most important) 2. Molded
Summarize 2 ways in which tablet ingredients may play an important role in the finished product:
1. Imparting satisfactory processing & compression characteristics on the formulation 2. Providing additional desirable physical characteristics to the finished tablet
What are the 3 important properties that lubricants possess in the manufacturing of tablets?
1. Provides a glidant effect by coating and lubricating particle surfaces -> improves flow properties of tablet granulation 2. Provide anti-adhesive effects -> prevents adhesion of material to punches and dies during tablet compression 3. Acts as as lubricant between the walls of the die cavity and tablet, facilitating tablet ejection
What is the concentration of lubricants used in a formulation?
< or = 1%
What effect do mannitol, lactose and sorbital all produce in a tablet?
A cooling effect in the mouth - particularly in chewable tablets
What is the role of a glidant in a formulation?
A glidant is used primarily to improve the flow characteristics of a powder or granulation.
What is a tablet?
A tablet is a solid dosage form that is prepared by compression or molding.
Provide an example of the range of diluent concentration that can be found in a tablet:
A. Aspirin 650 mg: large dose, small amount of diluent B. Levothyroxine 0.05 mg: very small dose, large amount of diluent
Which flavouring agents are present in tablet formulation?
Artificial concentrations used: peppermint, vanilla, cherry, etc. in small quantities
Why is it preferable to wet powders with a binding agent in solution?
Because powder differ with respect to the ease with which they can be wetted.
Which granulation process incorporates the addition of binders?
Binders are added ONLY in wet granulation - this is different from the "direct compression binders" or "excipient binders" which are designed specifically for direct compression.
What properties do starch and MCC both possess?
Binding & disintegrant properties
What property do dextrose, sucrose & lactose all exhibit?
Binding properties
What is the most commonly used glidant?
Colloidal silicon dioxide (Cab-O-Sil) @ a concentration of < or = 1%
What percentage of the tablet does the diluent normally comprise?
Comprise as little as 5% to as much as 80% of the total weight of the tablet
What is generally more effective, dry form or wet form for addition of binders?
Dry binding agent is not as effective in reaching and wetting each of the particles within the mass of powders, as the film of adsorbed air on the surface of particles must be penetrated before the powder can be wetted by the binder solution
What is granulation?
Granulation: the process of particle size enlargement of powdered ingredients
What property do lactose and sucrose impart on tablets?
Hardness
What does a tablet contain?
It contains 1 or more medicinal (active) substances, and may include other components such as diluents, binders, coatings, disintegrates and colorants.
What types of tablets are diluents more important in?
It is easier to attain uniformity when making large tablets as opposed to smaller ones - more important when dealing with potent, low dose drugs
At what point are lubricants added to a formulation?
Lubricants are usually the last item to be added to a formulation, and are generally added dry at the point when all other components are in a homogenous state. Each granule must be coated with lubricant. To ensure this, it is added as a very fine powder.
On what principles are the method of preparation and added ingredients selected for a particular tablet?
Prep method & ingredients are selected in order to give the tablet formulation the desirable physical characteristics that allow for the rapid compression of tablets. However, we must be aware of how these ingredients and methods of preparation affect the availability of the API and ultimately the therapeutic efficacy of the dosage form.
What is the obstacle with turning powders into compressed tablets?
Simple powders may have poor flow and compression characteristics. They require tremendous pressure and the resulting tablet may not have desired characteristics (hardness, disintegration, etc.)
Why is the amount of binder found in a formulation so critical?
Sufficient binder is necessary to maintain an intact tablet during transit, dispensing and handling. Too little = fragile tablets Too much = excessive hardness - slow disintegration, dissolution, poor bioavailability
What is a compressed tablet?
Tablets formed by compression contain no special coating. They are made from powdered crystalline or granular materials alone or in combination with binders, disintegrants, lubricants, and diluents - and in many causes, colorants. They occasionally contain flavouring agents.
Can a substance perform both lubricant and glidant activity?
Talc for example, can possess both lubricant and glidant properties. Some formulations include different agents for each function, ex: magnesium stearate (lube) and Cab-O-Sil (glidant). ** A lubricant may possess glidant properties; but a glidant does not possess all of the lubricant's properties - therefore, a distinction between the 2 is made
What is the concentration range of binder within a tablet?
The concentration of binder varies from 1-20% of the dry weight of a tablet formulation.
What do starch, kaolin and dextrose do to a tablet formulation?
They add softness to the tabs
How are tablet ingredients classified?
They are classified based on the function they perform.
Are sweeteners and flavouring agents required for tablets?
They are required for chewable and effervescent tablets, but NOT for standard compressed tablets, which are intended to be swallowed
How do sodium bicarbonate, citric & tartaric acid work as disintegrants?
They lead to the evolution of CO2 when exposed to water (this is used for effervescent tablets)
Name 3 water insoluble lubricants:
- Magnesium stearate - Stearic acid - Talcum
How can we resolve the issues regarding turning powders into tablets? (2)
- Modification to the materials that require compression - Various processing methods that result in the formation of granules which impart both cohesiveness and flow properties on the powder
Describe starch (corn starch) as a disintegrant:
- One of the most effective and widely used agents - Added as a dry powder - If added as a pass, used as a binding agent (not an effective disintegrant in this form) - Usually concentration of 5% w/w
What is the purpose of a disintegrant? (3)
- Facilitates the break-up of a tablet after administration - Causes the tablet to rupture or break apart when it comes in contact with aqueous fluids with the GI tract - Facilitates disintegration, dispersion, and dissolution of tablets
Describe the mechanism of disintegration:
- Involves porosity, capillary action and swelling - Disintegrants are hypothesized to draw gastric fluids into the tablet, causing the tablet to swell and finally break up due to hydrostatic pressure
What is the purpose of diluents (fillers)? (3)
- Act as a vehicle/carrier for the drug - Increase the bulk of the tablet - Help improve or maintain the content uniformity
What are the basic requirements of formulations that have been developed for tablet dosage forms? (7)
- Adequate flow of the tableting mix in the machine hopper and uniform fill into the dies - Sufficient cohesive properties to form a firm, strong tablet under compression - Lubricant properties which prevent binding of the tablets and punches in the dies - Must not adhere to the punches and the dies - Uniform drug dose in each tablet - Satisfactory release of the drug from the tablet after administration - Capability to be processed on high speed production equipment
What are the two factors that must be kept in mind while choosing the prep method & excipient ingredients of a tablet?
- Availability of the API - Therapeutic efficacy
How should binders be added to a formulation?
- Binders such as starch, gelatin and glucose can be added to bulk powder in dry form or as a solution - The same amount of binder is most effective as a solution
What 2 concerns are prevalent when considering the significance of disintegrants in tablet manufacturing?
- Bioavailability - Bioequivalence
What are 4 other disintegrants (beyond starch)?
- Celluloses (microcrystalline cellulose, methylcellulose) - Clays (bentonite, Veegum) - Gums (acacia) - Sodium bicarbonate, citric or tartaric acid
What types of tablets are available? (7)
- Chewable - Sugar coated - Film coated - Gelatin coated - Enteric coated - Buccal or sublingual - Effervescent (fizzy)
What are the various classes of tablet ingredients? (7)
- Diluents - Binders - Lubricants - Glidants - Disintegrants - Colouring agents - Flavouring agents
Why are tablets the most frequently used dosage form? (7)
- Economical (preparation & shipping) - Relatively easy to prepare - Easy to package, ship and dispense - Good stability, especially if coated - Provide accurate dosing - Easy for patients to carry and administer - Relatively tasteless, especially if coated
What is the purpose of adding colouring agents to tablets?
- Enhancement of aesthetic quality (elegance, attractiveness) - Provide distinctiveness to the product/ to aid in product identification ** Colorants must be approved by regulatory bodies (FDA or HBP) and are subjected to rigid toxicity standards, as in the past, certain dyes have been found to be carcinogenic
List some common diluents: (6)
- Lactose - Dextrose - Microcrystalline cellulose (MCC) - Starch - Dicalcium phosphate - Mannitol
