PDD 08: Solid Oral Dosage Forms – Excipients Flashcards
What are dosage forms?
- different manners of drug substances present in market
- unique in their physical and pharmaceutical characteristics
- determines the physical form of the final pharmaceutical preparation
- drug delivery system formed by technological processing
- reflect therapeutic intentions, route of administrations, dosing etc.
What are some oral dosage forms?
- tablets
- capsules
- powders
- solutions
- syrups
- suspensions
- magmas
- gels
What are some parenteral dosage forms?
- solutions
- suspensions
What are some intraocular dosage forms?
- solutions
- suspensions
- ointment
What are some sublingual dosage forms?
- tablets
- troches
- lozenges
What are some intravaginal dosage forms?
- suppositories
- cream
What are some intranasal dosage forms?
- solutions
- sprays
- inhalations
What are some intrarectal dosage forms?
- suppositories
- cream
What are some conjunctival dosage forms?
- contact lens inserts
- ointments
What are some solid dosage forms?
- tablets
- capsules
- powders
What are some liquid dosage forms?
- solution
- syrup
- emulsion
- suspension
What are some semi-solid dosage forms?
- cream
- paste
- gel
What are some gas dosage forms?
- inhaler
- aerosole
What are the advantages of oral solid dosage forms?
easier to patients:
- non-invasive
- easy administration
- portable
- palatable
easier to manufacturers:
- established manufacturing process
- accurate dosing
- drug stability
- easy to package, ship, and store
What are the disadvantages of oral solid dosage forms?
patients:
- GI tract irritation
- swallowing (large tablets/capsules)
manufacturers:
- poor oral bioavailability/poor water solubility
- formulations difficulties
What are the types of tablets?
- compressed
- film coated
- enteric coated
- rapid dissolving
- layered
- sugar coated
- effervescent
- controlled release
What do active pharmaceutical ingredients (APIs) do?
alter biological conditions
What do excipients do?
various actions during manufacturing, storage, and use
What is a pharmaceutical excipient?
pharmacologically inactive substances (no therapeutic effect) added to the API during product formulation to improve or modify:
- bioavailability
- stability
- manufacturing
- drug release
- flavour
What are the ideal properties of pharmaceutical excipients? (4)
(all components must work together to create the desired product)
- no interaction with drug
- cost effective
- pharmacologically inert
- stable for handling
What are the types of excipients? (8)
- diluents
- binders
- disintegrants
- lubricants
- glidants
- colourants
- sweeteners
- flavouring
What are diluents?
make up largest proportion of tablet weight and volume
- typical tablet weighs > 50 mg
- imagine the difficulty of accurately dosing and handling potent APIs without a diluent
What do diluents do? (2)
- dilute the drug
- increase bulk volume of tablets for ease of handling
What are the characteristics of a good diluent? (7)
- chemically inert
- hydrophilic/water soluble
- non-hygroscopic
- palatable
- compactable
- cheap
- biocompatible
What are some common diluents?
- lactose
- cellulose
- inorganic diluents
What is lactose?
- most common diluent
- readily soluble in water
- palatable
- non-hygroscopic
- good compactibility
- inert
What is cellulose?
- second most common diluent
- compactable
- inert
- hygroscopic
- can also act as a binder/disintegrant
What are inorganic diluents?
- calcium phosphate
- calcium carbonate
- excellent compactibility
- might interact with acids or base sensitive APIs
What does selection of excipients require?
empirical testing and experience
- hundreds of products are available for each type of excipient
What do binders do?
- important for tablet manufacturing
- acts as adhesive to hold granules together
- varying proportion of tablet formulation (1-20% w/w)
What are some common binders?
- starch
- polyvinylpyrrolidone (povidone)
- carboxymethyl cellulose
- microcrystalline cellulose
- acacia (Gum Arabic) forms very hard granules
- sucrose and other sugars
- gelatin
- polyethylene glycol
What do disintegrants do?
allow the tablet to break apart in the GI tract
What is the disintegration time of tablets?
regulated by Pharmacopeia, ranging from 3 minutes for soluble tablets up to several hours for extended release formulations
What is the mechanism of action of disintegrants?
- facilitate water uptake to wet drug particles and excipients
- swelling of disintegrant leads to rupture of tablet structure
What is the main mechanism of disintegration?
capillary action (wicking), swelling and strain
recovery
- disintegrants do not necessarily need to be soluble
- in order to work properly disintegrants must be uniformly distributed through powder/granule mixture
- added in varying proportion of tablet formulation (1-20% w/w)
What are some common disintegrants?
- starch
- crosslinked polyvinylpyrrolidone (crospovidone)
- sodium starch glycolate
- sodium croscarmellose
- microcrystalline cellulose
What is starch?
- partially water soluble, especially at higher temperatures
- large surface area for water adsorption
What is crosslinked polyvinylpyrrolidone (crospovidone)?
- not soluble in water
- readily absorbs water to promote swelling
What is sodium starch glycolate?
- carboxymethylated starch (higher solubility than starch)
- can be internally crosslinked to form
What is microcrystalline cellulose?
- derived from partially depolymerized cellulose
- degree of polymerization typically <400
- can also act as a binder/diluent
What do lubricants do?
reduce friction between particles
What are lubricants added for?
ensure tablet formation and ejection occurs without friction
What are lubricants?
- often hydrophobic and may reduce dissolution times
- small fraction of tablet composition (0.5-3%)
What are some common lubricants?
- magnesium stearate
- stearic acid
- polyethylene glycol (PEG) 4000-8000
- sodium lauryl sulphate
- liquid paraffin
What are glidants used for?
- added to the powders prior to compression to improve the flowability of powder or granules
- forms a film over particles to create a smooth surface
Why is flowability of tablet mass important?
critical for high production speeds
What are some common glidants?
- colloidal silicon dioxide (Aerosil)
- talc (Mg6(SiO2)4(OH)4)
- titanium dioxide
- magnesium stearate
What are the functions of colorants?
- added for pharmaceutical elegance
- increase compliance by creating optically attractive formulations
- identification/branding
- batch-to-batch uniformity
- increase stability of photosensitive APIs
What are the various classes of colourants used?
- organic dyes (ie. Erythrosine, Sunset Yellow, Patent Blue V)
- lakes (FD&C colours on a surface of alumina or other carriers, creates fast drying opaque layer)
- inorganic colours – ie. ferric oxide (high light stability)
- natural colours such as vegetable or animal colours
What are the functions of sweeteners?
taste masking
What are sweeteners important for?
lozenges, pediatric formulations, sublingual tablets, etc.
What are sweeteners generally less of a consideration for?
tablets that are swallowed whole
What are the two types of sweeteners?
- bulk sweeteners
- intense sweeteners
What do bulk sweeteners do?
add texture and bulk to the formulation and usually make up large proportion of tablet
What do intense sweeteners do?
provide sweetness at low concentrations
What does the choice of sweetener depend on?
technical, regulatory, pharmacological considerations
- patient population: caloric content, comorbidities (ie. aspartame cannot be metabolized by patients with Phenylketonuria)
- flavour profile: many artificial sweeteners have unpleasant aftertaste
- chemical compatibility – ie. phenylalanin plus aspartame results in poor heat and acid stability
- processability
What is the function of flavouring agents?
added to give tablets addition taste or flavour, particularly for taste masking
- especially important for pediatric formulations
What does flavouring usually match?
matches the colour to improve acceptability
Where do flavouring agents come from?
- derived from natural or synthetic sources such as menthol, vanillin, fruit flavours, etc.
- sweeteners such as sucrose and sorbitol sometimes added as flavouring agent
