Science of Medicines Week 30 Flashcards
(115 cards)
1
Q
define capsule
A
the drug and excipients are contained in a gelatin ‘shell’
2
Q
define caplet
A
a compressed powder in the shape of a capsule
3
Q
What are 8 types of tablets available?
A
- uncoated
- sugar-coated, film-coated, press-coated
- controlled release
- effervescent
- soluble
- chewable
- sublingual
- lozengers
4
Q
What are some advantages of tablets?
A
- accurate dosing
- convenient
- better stability than liquid
- rate of drug release can be altered
- mass production
- simple and cost effective
- widely accepted by patients
5
Q
What are some disadvantages of tablets?
A
- swallowing
- low solubility drugs
- taste issues
- oxygen and moisture sensitivity - needs coating?
6
Q
What are the 6 most important properties of tablets?
A
- accurate and uniform dose
- same weight, appearance and size
- recognisable shape
- must withstand stress of manufacturing
- good dissolution rate
- moisture and temperature stability
7
Q
Which 3 properties do particles need to be formulated into a tablet?
A
- particles must be sufficiently free flowing
- particles must stick to form a tablet when applying force
- adhesion of the tablet must be AVOIDED
8
Q
What are the 8 steps of making a tablet?
A
- weighing
- dry mixing of API and excipients
- granulation - agglomerating fine powders
- tableting
- quality control check
- coating
- dissolution check
- quality assurance check
9
Q
When you apply force to a powder, which stages does the powder undergo?
A
stage 1 = rearrangement
stage 2 = deformation
stage 3 = bonding
10
Q
stage 1
A
rearrangement of the powder bed when applying stress
11
Q
stage 2
A
deformation of the powders due to applied force
12
Q
stage 3
A
binding of the compressed powders
13
Q
What happens in stage 1 (rearrangement)?
A
- when applying intial force, the powder bed undergoes densification and particles rearrange to minimise free space between them
- as pressure increases, particle movement is not possible, and deformation (stage 2) occurs
14
Q
What happens in stage 2 (deformation)?
A
when the particles are so closely packed that no filling of space can occur so further increase in force causes the powder to undergo deformation
15
Q
What are the 3 main types of deformations of particles?
A
- elastic deformation
- plastic deformation
- brittle deformation
16
Q
Which do we NOT want?
A
brittle deformation - the tablet will break up on removal of force
17
Q
What are examples of materials that undergo plastic deformation?
A
- MCC
- stearic acid
- starch
- sodium chloride
18
Q
What are examples of materials that undergo fragmentation?
A
- sucrose
- lactose
- calcium carbonate
19
Q
What happens in stage 3 (bonding)?
A
inter-particle bonding occurs resulting in the formation of a tablet
20
Q
What is the direct compression method?
A
a tablet manufacturing method where a powder blend of active ingredient and excipients is directly compressed into tablets without the need for granulation or other intermediate steps
21
Q
What are the 3 main steps of direct compression?
A
- size reduction
- dry mixing
- compression
22
Q
What happens in size reduction?
A
- the size of particles is decreased leading to a larger surface area, which allows better flowability and dissolution
- micronisation and milling can be used
23
Q
What happens in the dry mixing stage?
A
- powders are mixed to ensure uniformity throughout the drug
- all ingredient must be free of lumps
- sieving helps this
24
Q
What happens in the compression stage?
A
- a compressible vehicle is dry blended with API, also a lubricant, flow agent and disintegrant if needed
- blend is compressed
- must ensure we have the desired particle size of the API
25
What are examples of common compressible vehicles?
anhydrous lactose, MCC, starch, dicalcium phosphate
26
What are the 7 typical components of a direct compression tablet?
1. API
2. diluent
3. lubricant
4. disintegrant
5. glidant (flow agent)
6. flavours/colours
7. binding agent
27
define granulation
the process by which primary powder particles adhere to form larger particles called granules
28
Why is the granulation method used most of the time over direct compression?
granules are much easier to compress than powders - makes compression easier
29
How are bonds formed when making powders into granules?
either by compression or via a binding agent
30
What is the most popular type of granulation method used in industry?
wet granulation
31
What are the properties of granulated particles?
1. good flow properties
2. increased compressability
3. resistance to agglomeration
4. reduction in dusting
32
What are the steps of wet granulation?
1. grinding down the drug
2. mix drug with a binder and maybe intra-granular excipients
3. put mixture into mixer or granulator
4. pass through wet screen - forced into uniform granules
5. mixture dried in fluidised bed dryer
6. mixture is blended with excipients (extra-granular)
7. mixture undergoes compaction
33
define granulating solvent
a liquid, often water or an alcohol-based solution, used in wet granulation to bind powder particles together and form granules
34
What are the most common granulating solvents?
water, ethanol and isopropanol
35
Why are there only a few solvents available to be used in granulation?
we cannot eliminate all the solvent upon drying
36
What are the overall steps of wet granulation?
1. dry mixing
2. wet massing
3. size enlargement (produces granules)
4. drying
5. size fractionation (screen)
6. dry mixing
7. compression
37
What are the 2 types of excipients added during wet granulation?
1. intragranular excipients
2. extragranular excipients
38
define intragranular excipients
excipients that are added at the beginning of manufacture, before wet mixing and goes into the granules
39
define extragranular excipients
excipients added after wet mixing that go towards forming the overall tablet - outside the granules
40
What are examples of intragranular excipients?
1. active drug
2. filler
3. binder (usually aqueous polymeric solution)
4. disintegrant
41
What are examples of extragranular excipients?
1. lubricants
2. glidants
3. disintegrants again
42
What is another name for dry granulation?
slugging
43
When is dry granulation used?
when powder blends cannot be directly compressed due to poor flow or compression issues OR when heat or moisture-sensitive drugs are used (aspirin, vitamins)
44
What are the steps of dry granulation?
1. the formulation ingredients are mixed and pre-compressed on a tablet press at much higher pressure than usual
2. the slug that forms is then ground into uniform size granules
3. compressed into tablet
45
What are the advantages of dry granulation over wet granulation?
1. more economical
2. less equipment and space needed
3. no need for moisture or heat
4. can cope with wide range of materials
5. process easily scaled up
6. mechanical strength of the product will be uniform
46
define capsule
an edible shell filled with a formulation to produce a dose
47
What are the 2 broad categories of capsules?
1. regular capsules
2. controlled-release capsules
48
What are the 2 types of regular capsules?
1. hard gelatin or HPMC
2. soft gelatin or HPMC
49
What is HPMC?
hydroxypropylmethylcellulose
50
Why is HPMC often used to make capsules?
for patients who cannot have gelatin due to veganism or religion
51
What are the 2 types of controlled released capsules?
1. coated granules
2. coarse dispersion
52
When are capsules used over tablets?
if a drug is unable to be compressed
53
What is gelatin?
a protein substance commonly derived from collagen in the tendons, ligaments and tissues of animals
54
What are the 2 types of gelatin?
Type A and Type B
55
Why is gelatin good for capsules?
the films it makes are soluble in biological fluids at body temperature
56
define dipping
when stainless steel pins are dipped into a solution of gelatin at controlled temperature - to form capsule shell
57
Which 2 parts do hard gelatin capsules have?
a cap and a body - they fit inside each other
58
How are soft capsules different to hard capsules?
they are made and filled in one preparation - one part
59
What may be added to gelatin solution to make capsules soft and elastic?
a plasticiser such as glycerol, sorbitol
60
define dosator
a device used to fill capsules
61
How is the fill weight for a dosator adjusted?
by adjusting the powder bed height and dosator pin position
62
What does the uniform capsule filling depend on for hard gelatin capsules?
the flowability of the powder
63
What else is required in hard shell capsules for low-dose drugs?
diluents
64
What is used for hard shell capsules to decrease friction and improve flow into capsule shell?
glidants and lubricants
65
What are examples of non-powder fillings for hard gelatin capsules?
1. granules and pellets
2. multiparticulates
3. semisolids
4. non-aqueous liquids
66
What are the 4 potential issues with hard shell capsules?
1. crosslinking
2. embrittlement
3. sticking/solvation
4. leaking
67
What happens in crosslinking?
1. gelatin is made of proteins and sometimes the protein chains bond together more than they should
2. this makes the capsule tougher and can make it insoluble - drug can't dissolve
68
What happens in embrittlement?
1. the capsule loses water to either the drug or air and dries out
2. becomes brittle and can crack
69
What happens in sticking/solvation?
1. moisture gets onto capsule and it can absorb water
2. makes capsule sticky or partially dissolves it
70
What happens in leaking?
1. the body and cap may not seal properly or some drug gets caught in the seal
2. contents can leak out
71
What are vegetarian capsules (Vcaps) made from?
hydroxypropylmethylcellulose (HPMC), starch, pullulan or PVA
72
What is the structure of soft gelatin capsules?
made of a continuous gelatin shell surrounding a liquid or semi-solid matrix material
73
What are soft gelatin capsules good for?
compounds which are soluble or can be dispersed in oil, hydrophilic liquids or both
74
What are advantages of soft gelatin capsules?
1. no need to compress drug
2. no flow issues as drug is dispersed or dissolved in liquid
3. higher chemical stability of dispersed drugs due to oily vehicle protecting from water
4. drug formulations as self-emulsifying oils (SEDDS) increase oral bioavailability
75
What are drawbacks of soft gelatin capsules?
1. some drugs or excipients with high concentration of water cannot be incorportated - dissolve gelatin
2. emulsifiers used in emulsions can affect capsule sealing
3. emulsions may become unstable with water loss
76
What are the 3 main types of coatings used?
1. film coating
2. sugar coating
3. press coating
77
Why do we coat tablets?
1. taste masking
2. protect ingredients from environment
3. easier to swallow
4. identification
5. enteric or controlled-release or coat multi-particulates
78
What are the 6 steps of producing a sugar coating?
1. sealing
2. sub-coating
3. smoothing
4. colouring
5. polishing
6. printing
79
sealing
sealing the tablet core to prevent entry of water (usually using shellac)
80
sub-coating
adding calcium carbonate or talc in a sucrose solution to sub-coat the tablet to create a rounded shape
81
smoothing
applying sucrose syrup to smooth
82
polishing
using beeswax and carnauba wax to create a high gloss surface finish
83
printing
manufacturer's logo or code is printed on
84
How is film-coating done?
1. a thin film of polymer is deposited, usually by spraying, onto the tablet
2. the coating liquid (either solution or suspension) contains a polymer in a suitable liquid
3. drying allows removal of solvent
85
What are the 4 potentials issues with coating?
1. picking/chipping
2. roughness
3. sticking
4. film cracking/peeling
86
picking/chipping
small pieces of the coating flake off
87
roughness
bumpy feel to tablet - hard to swallow and unattractive
88
sticking
tablets stick together, damaging coatings
89
film cracking/peeling
the coating develops cracks or peels off, exposing the tablet core to the environment, reducing stability
90
define enteric coating
a coating the protects the tablet core from disintegration in the acid environment of the stomach
91
What are the 4 main reasons for enteric coating?
1. preventing acid attack on drugs
2. protects stomach from irritant drugs
3. absorption further down GI tract
4. taste masking
92
How must pH-sensitive polymers behave?
1. insoluble at low pH
2. rapid increase in solubility with increasing pH from a specific pH
93
Which ways can enteric-coating be done?
both sugar-coating and film-coating
94
How is sugar coating for enteric coatings done?
the first sealing layer is changed from the usual shellac to an enteric polymer
95
How is film coating for enteric coatings done?
enteric polymers are used as the film
96
What are examples of polymers used for enteric film coatings?
cellulose acetate phthalate (CAP), polyvinyl acetate phthalate (PVAP) or another acrylic derivative
97
How much more enteric polymer must be applied to ensure protection compared to a basic film coating?
2-3x more
98
How do delayed-release tablets work?
enteric coatings are used to ensure the drug stays inside the coating until reaching the small intestine - lag in onset time
99
What are the steps of dissolution of a delayed-release tablet?
1. drug core coated with delayed release membrane
2. exposed to pH of the small intestine causes the coating to dissolve at higher pH
3. the drug core is now exposed and undergoes dissolution
100
What are the 3 key properties of enteric coating polymers?
1. free carboxylic acid groups
2. insoluble at low pH
3. have a sharp increase in solubility at a specific pH
101
Why do enteric coating polymers need free carboxylic acid groups?
stay dissolved at low pH, and ionise at higher pH
102
define multi-particulates
tiny spherical particles of drug and each acts like a mini-tablet and are coated individually to control drug release
103
How are multi-particulates used for controlled-release medicines?
the multiparticulates are coated individually and can be filled into a sachet, capsule or compressed into a tablet
104
How do multi-particulates allow better drug distribution?
there are many drug particles, not just one big mass of tablet in one area
105
What are benefits of multiparticulate coatings?
1. better flow in GI transit as broken into tiny particles
106
What are drawbacks of multi-particulate coatings?
1. hard to control the coating completely with uniformity
2. difficult to retain in upper GI tract
107
How are spheronised granulates made?
the drug granulate is forced through a mesh under pressure to form small particles for spheronisation
108
What are the 3 types of drug release mechanisms from multi-particulates?
1. diffusion
2. osmosis
3. erosion
109
diffusion release
water in the GI tract enters the particle by diffusion and the drug dissolves inside the pellet and diffuses through its coating
110
osmosis release
water enters the pellet, and osmotic pressure builds up, forcing the drug out
111
erosion release
coating degrades naturally with time
112
Why shouldn't you take enteric-coating tablets or capsules with an antacid?
these cause the pH of the stomach to rise, causing drug release in the stomach
113
define multiple-unit pellet system (MUPS)
when enteric-coated multiparticulates are compressed into a tablet
114
Why are MUPS absorbed much faster than normal enteric-coating capsules?
as the tablets disintegrates into many small pellets and the smaller particles move faster through the stomach into the intestine
115
