Routes of administration - oral (tablets) Flashcards
Describe the physiology of stomach.
Acid secretion: pH 1-2 (fasted), 4-5 (fed)
Surface area: ~0.05m2
Transit time: 0- >3h (depending on food intake)
Describe the physiology of the small intestine.
Pancreatic and biliary secretions: pH 5-7
Surface area: ~200m2
Transit time: 3-4h (independent of food intake)
Describe the physiology of the large intestine.
pH 6-7.5
Surface area: ~0.35m2
Transit time: highly variable
Compare the GI tract when fasted vs fed
Increase in pH (less acidic)
Increase in fluid volume
Increase in bile salt (solubilisation)
State the advantages of oral route
Most common route - 60% of medicines are orally administrated
Simplest, convenient & safe - no associated infection risk
Modified release formulations available
High surface area with good absorptive capacity - good blood supply
State the disadvantages of oral route
Slower onset of action - dissolution is often the rate limiting step
Variable absorption - absorption changes with age, gender, food etc
- disease state
Hostile environment - GI secretions, enzymes, pH
First pass metabolism
Difficult to reverse therapy
GI irritation
Define tablets.
Solid preparations each containing a single dose of one or more active substances.
How are tablets obtained?
By compressing uniform volumes of particles or by another suitable manufacturing technique such as extrusion, moulding or freeze-drying.
State the advantages of tablets.
- Convenient to take and handle
- Better chemical, physical and microbiological stability, compared to liquid dosage form - longer shelf life
- Precise dosing of drug
- Relatively cheap to mass produce with consistent quality
What are the quality attributes of tablet?
- Include the correct dose of drug
- Be consistent in weight, size and appearance
- Release drug in a controlled and reproducible manner
- Be biocompatible and not cause harm to patients
- Be of sufficient mechanical strength
- Be chemically, physically and microbiologically stable
- Be a product acceptable to patients
- Be packed in a safe manner
- Be resistant to attrition and fracture
What is the most common type of tablet.
Disintegrating tablets
How do disintegrating tablets work?
Intended to be swallowed and to release the drug in a relatively short time to aid fast and complete drug release once in digestive fluids.
Describe gastro-intestinal tablets.
- They are delayed-release tablets
- Intended to resist the gastric fluid and to release the drug in the intestinal fluid.
- Prepared by covering the tablets with a gastro-resistant coating/from granules/particles already covered with a gastro-resistant coating
Describe modified-release tablets.
- Coated or uncoated tablets that contain special excipients or are prepared by special procedures, or both, designed to modify the rate, the place or the time at which the drugs are released.
Describe the release the modified-release tablets.
- Prolonged-release - drug is released slowly at a constant rate
- Delayed-release - drug is released some time after administration
- Pulsatile-release - drug is released from the formulation in two or more pulses.
What are the three dispersible tablets?
- Dispersible
- Orodispersible
- Soluble
Describe dispensible tablets.
Can be coated or uncoated - intended to be dispersed in water before oral administration, giving a homogenous dispersion
Describe orodispersible tablets
Uncoated tablets - intended to be placed in the mouth where they disperse rapidly before being swallowed
Describe soluble tablets.
Can be uncoated or film-coated - intended to be dissolved in water before administration
Describe effervescent tablets.
Uncoated tablets intended to be dissolved or dispersed in water before administration.
What do effervescent tablets contain?
A weak acid and a carbonate/bicarbonate which react rapidly in the presence of water to release carbon dioxide.
What is the advantage of the high carbonate contents in effervescent tablets?
- Results in a buffer solution temporarily increases stomach pH
- Leads to fast emptying of stomach content
- Allows drugs tp enter the intestine faster for absorption.
- Provides a faster drug absorption and minimise stomach irritation.
Describe sublingual and buccal tablets.
Sublingual - placed under the tongue
Bacall - placed in the buccal cavity
- the side of the cheek
- High up between the inside of the upper lip and gum
They are often small and porous
Provide rapid drug release for systematic effect without first-pass liver metabolism
Describe lozenges and pastilles.
- They are solid, single-dose preparations
- Lozenges are hard whereas pastilles are soft/flexible
- Both intended to dissolve or disintegrate slowly in the mouth when sucked - for local effect in the oral cavity and the throat
What is the most common technique of tablet manufacturing?
Powder compression
Describe tablet manufacturing.
- Requires two punches and a die
- When force is applied, bonds are formed between particles during compression and a coherent compact is formed.
What are the three main stages in tablet formation?
- Die filling
- Tablet formation
- Tablet ejection
State the two main tablet presses.
- Single-punch press
- Rotary press
What are the properties of a powder mix that must be controlled for successful tablet formation?
- Homogeneity and segregation tendency: under-/over-mixing, segregation into different particle sizes.
- Flowability: filing of the die controlled by gravity
- Compression and compaction
- Friction and adhesive properties: can damage punch/die or tablet
Why are excipients included in a tablet?
To ensure tableting runs satisfactorily and tablets produced are of specified quality.
What are the commonly used excipients?
- Filler
- Disintegrant
- Binder
- Anti-adherent
- Lubricant
- Glidant
Describe filler.
- Tablets normally weigh >50mg for ease of handling
- Added to increase the bulk volume of the powder and hence the tablet size
State the advantages of lactose.
- Readily dissolved in water
- Pleasant taste
- Non-hygroscopic
- Good compactability
What is the most common tablet filler?
Lactose
What is the limitation of lactose filler?
Lactose intolerance
Describe disintegrant.
- Allows tablet to break up into small fragments when in contact with a liquid
- Promotes rapid drug dissolution thus bioavailability
What is the most commonly used disintegrant?
Starch
What is the advantage of using starch as the disintegrant?
- Swells in contact with water
- The swelling disrupts the tablet to provide larger surface area during dissolution
Describe binders.
Ensures granules and tablets can be formed with the required mechanical strength
What are the two ways binders can be added to a drug-filler mixture?
Powder - microcrystalline cellulose
Solution - starch, sucrose, gelatine and polymers
Describe glindants.
Improves powder flowability by reducing cohesion between particles
Which three glidants can be used?
Talc
Colloidal silica
Magnesium stereate
Which of the three glidants is more commonly used?
Sate the advantage of this glidant
Colloidal silica at ~0.2%
- particles are very small
- adhere to particle surface of other ingredients
- reduce inter-particulate friction thus improve flow
Describe lubricants.
- Lowers friction between the solid ingredients and the machine wall
- Improves tablet formation and ejection
- Added in almost all tablet formulations
Which lubricant is most widely used?
Magnesium stearate
Describe anti-adherent.
- Reduces adhesion between powder and the punch faces
- prevents particles sticking to the punches
- Particularly important if tablet punches have markings
