L51 - Solid dosage forms - role of excipients Flashcards
1
Q
What are reasons why we don’t administer pure drugs?
A
- dose
- taste
- physical properties (solubility, partitioning, bioava, stability)
- control rate of absorption
- allow administration via specific routes
- handling, transport, marketing
2
Q
why formulate to control dose?
A
- patient unlikely to measure amounts
- difficult to manufacture - blend uniformity
3
Q
What are issues with dose?
A
- high dose (low potency) problem to formulate
- poor flow/compressibility cannot make a tablet
4
Q
What are issues with taste?
A
- subjective, difficult to quantify
- many drugs are bitter
- mitigated by film-coating
5
Q
What do effervescent tablets contain that make them work?
A
sodium bicarbonate
6
Q
how do effervescent tablets work?
A
- increase rate of disintegration, dissolution, gastric emptying
- faster absorption = faster onset
7
Q
What is an excipient?
A
- all other components of a formulation other than active drug
- chemically and physiologically inert
8
Q
what are uses for excipients?
A
- aids processing of the system during manufacture
- protect, support, enhance stability, bioavab/acceptability
- assist in product identification
- enhance overall safety and effectiveness of drug during storage and use
9
Q
what are common pharmaceutical excipients?
A
- lactose, micro crystalline cellulose - diluent, compressive
- sodium bicarbonate - effervescent
- magnesium stearate - lubricant
- colloidal silicon dioxide
10
Q
what are roles of excipients on dissolution?
A
- rate of drug dissolution affected by choice of formulation additives
- tabletting lubricants is troublesome
- insoluble Mg stearate imparts hydrophobicity, inhibiting drug dissolution
- minimise % of lubricant in solid dosage form
11
Q
What are diluents?
A
- bulking agents
- make reasonable sized tablets
12
Q
what are examples of diluents?
A
- lactose - pleasant taste, dissolves rapidly in water, not hygroscopic
- dicalcium phosphate in wet granulation - insoluble in water, less hygroscopic
- starches as diluents and binding agents - moisture uptake
13
Q
What is microcrystalline cellulose?
A
- produced by partial hydrolysis of cellulose
- compressibility and high tablet strength from low compression forces
14
Q
what is microcrystalline cellulose like? (properties)
A
- lubricant
- disintegrating properties
- sensitive to lubricant - hinders strong bonds forming between layers
- moisture sensitive
15
Q
what are the various grades of MCC?
A
- particle size - 90, 200, 15 mcm
- low moisture grade - reduced compression
- higher bulk density - blending
- low bulk density - increase tablet strength
16
Q
what are lubricants used for?
A
- prevent adherence to punches and dies
- smooth ejection of tablet from die
17
Q
what are examples of lubricants?
A
- // talc and Mg stearate punch lubricants
- // stearic acid as die lubricant
18
Q
what is Mg stearate?
A
- lubricant
- incorporated w/ dry granules before compression
- self-lubricating properties
19
Q
what are disadvantages of Mg stearate?
A
- additional processing steps
- inc conc dec disintegration time, drug dissolution, weakens bonding force
- red due to hydrophobic nature
- incompatible with many drugs
20
Q
what are role of glidants?
A
- added to tablet formulations to improve flow properties of granules
- act by red inter-particulate friction
- // fumed silica, synthetic amorphous colloidal silicondioxide
21
Q
What does the reduction in contact area between granules reduce?
A
- inter-particulate cohesion/adhesion
- determines flowability
22
Q
What are disintegrants used for?
A
- promote break up of tablets in vivo
- important in dissolution of insoluble drugs (high dose)
- to rapidly disintegrate tablet to inc SA of formed deaggregates = rapid release
23
Q
What happens to the tablet as it goes through the GI tract?
A
- disintegration to granules
- deaggregation to primary drug particles
24
Q
what are mechanisms of disintegrant action?
A
- swelling
- porosity, capillary action
- deformation
- gas production
25
how does capillary action work?
draws liquid into capillary pathways, rupturing inter-particulate bonds
26
what are super disintegrants?
- modified starch (Na starch glycollate) - rapid and extensive swelling with minimal gelling
- chem treated starch - more effective in lower conc
- red issues like compressibility and flowability
- more hygroscopic
27
what do binding agents do?
- bind powders together in wet granulation process/granules during direct compression
- liquid additives removed before compression
- can affect dissolution rate
28
what 2 ways can binding agents be added?
- powder in formulation
- solution to mixed powders in wet granulation
29
what are examples of binding agents?
- starch mucilage and gelatin
- polyvinylpyrrolidone (PVP) - soluble in water, releases drug rapidly
- 2-10% in granulating fluids
30
What are adsorbents?
substances capable of holding quantities of fluids in apparently dry state
31
what are examples of adsorbents?
- liquid flavourings, fluid extracts, oils mixed with adsorbent = granulated and compressed into tablets
- fumed silica, MC cellulose, kaolin and Mg carbonate
