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Lab 2 > Tablets and Coating > Flashcards

Tablets and Coating Flashcards

week:

1
Q

Describe the main excipients used in tablet manufacture, added to API:

5 names

A 
filler/diluent
disintegrant/ release modifier
binder (adhesive)
glidant
lubricant

colour/flavour

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2
Q

what excipient used to bulk up powder volume and give 3 examples?

A

filler/diluent

lactose
mannitol
cellulose

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3
Q

what excipient is used to aid disintegration and dissolution and give 3 examples

A

disintegrant

starch
sofium starch glycollate
crosslinked PVP

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4
Q

what excipient used in formation of granules and tabs with right mechanical strength

give some examples for wet and dry gran?

A

binder (adhesive)

wet gra

  • gelatin
  • PVP
  • Sucrose
  • starch
  • HPMC

dry gra

  • cellulose
  • methyl cellulose
  • PVP
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5
Q

what excipient used to improve flow properties, give 2 examples

A

glidant

colloidal silica 0.2%
talc 1-2%

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6
Q

what excipient used to ensure successful tab formation and ejection, and give 2 examples?

A

lubricant

magnesium stearate
stearic acid

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7
Q

what are the three main methods used in the manufacture of compressed tablets?

A

Direct compression/compaction
Wet granulation
Dry granulation

and melt granulation

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8
Q

what is added to the drug Independently of the method of compressed tab manufacturing chosen?

A

excipients

type and timing may change depending on method

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9
Q

what is step 1 of manufacture of compressed tabs:

direct compression?

A

blending with good flowing excipients

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10
Q

3 parts in direct compression

A

grind drug (PSR)
mixing (w excipients)
compression (tablet press)

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11
Q

difference between wet and dry granulation?

A

wet: high sheer blening/fluidisation/conti w binding liquid; drying and milling
dry: light compression of blend and milling e.g. roller compaction;slugging

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12
Q

Why use granulation in tablet manufacture?
(rationale/ benefits)
what can Granulation impact?

A
  • flow properties
  • mixing quality
  • compactability
  • dissolution
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13
Q

how can granulation impact dissolution?

A

if particles are hydrophobic/poorly soluble, dissolution is improved by mixing with hydrophilic filler and binder

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14
Q

granulation affect on:

a) flow
b) mixing

A

a) = decreases influence of cohesive forces (like), powder floww better :)
b) PSR used to ensure homogenous mixing + limit risk of demixing so = better mixing success :)

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15
Q

wet granulation steps to produce tablets (7)

A
  1. PSR of drug- direct compression
  2. mix w intragranular excipients
  3. mix powder blend w GF, binder
  4. Wet screen: sieve the wet mass produced
  5. Dry screen: dry grans- remove liquid
  6. mix w extragranualr excipients
  7. gran +excipient blend put through tablet press. compaction

final product tablets

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16
Q

why are granules passed through dry screen to remove liquid inw et granulation process of manufacture?

A

better control over granule size

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17
Q

what mixtures used in/ process of low shear- wet granulation

A

Low speed planetary mixers are used

Wet mass dried in a tray drier

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18
Q

low shear wet granulation

3 disads

A

(-) Manual transfer of materials required
(-) Long drying times
(-) Mixing issues due to tray drying

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19
Q

high shear granulation 4 ads?

A

(+) Lower amounts of water used vs. low shear granulation
(+) Short processing times
(+) End-point of granulation can be monitored
(+) Closed vessel and possible transfer to fluid bed drier

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20
Q

high shear granulation disad?

A

High shear mixer granulators are used.
Examples: Diosna, Colette Gral

Risk of overgranulation

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21
Q

Fluidised bed granulation process

A

Drug + excipients loaded into a fluid bed processor and fluidised with air
GF sprayed onto bed (from above) with a continuous stream of hot air

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22
Q

Fluidised bed granulation 2 ads?

A

(+) All steps completed in the same equipment

(+) Easy for the optimised process to be automated

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23
Q

Fluidised bed granulation 2 disads?

A

(-) Initial upfront cost to purchase equipment
(-) Extensive development work needed to optimise process
- Unlikely to have a one-size-fits-all solution that applies to all formulations

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24
Q

equipment used in Fluidised bed granulation can also be used in…

A

Fluidised bed mixing
Wet granulation
Fluidised bed drying

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25
Q

How can a spray-drier be used for granulation?

A

Dry granules obtained from a suspension or solution

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26
Q

Spray-driers for granulation

one ad and one disad?

A

(+) Produces free-flowing, hollow, spherical particles with good compaction properties

(-) Can = significant changes in material properties
- hard elastic materials can be made more ductile.

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27
Q

EXAMPLES OF INTRAGRANULAR EXCIPIENTS

used in wet granulation (3)

A
  1. Filler/diluent
    MCC: med diameter 50 microns
    good compactability
    lactose: fine grade= sufficient binding
  2. Binder (2-10% by weight)
  3. Disintegrant
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28
Q

EXAMPLES OF EXTRAGRANULAR EXCIPIENTS

used in wet granulation (2)

A

Disintegrant

Lubricant

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29
Q

role of binder added during wet granualtion?

A

Binder (2-10% by weight)
added as a dry powder to drug + filler
- water added during granulation

added pre-dissolved in water
- water content = 20-50% of the dry powder weight

need to balance tablet hardness vs. drug release

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30
Q

How does dry granulation work? what 3 processes

A

Granules formed under high pressure through

slugging (work hardening)
roller compaction
milling and sieving (same as wet gran)

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31
Q

Dry granulation

5 benefits of roller compaction over slugging method?

A 
(+) Cost effective
(+) Versatile method
(+) Easy to scale-up
(+) Uniform mechanical strength
(+) Gentler than slugging
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32
Q

process of dry granulation: 6 steps?

A
  1. grind drug (no GF used, particles aggregate under high pressure force = granule)
  2. mix grinded drug w intragran excipients
  3. no drying step. Roller compaction
  4. PSR: grind/screen/sieve
  5. mix w extragran excipeints
  6. Compress into tabs
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33
Q

how is PSR done in dry granulation? step4 after roller compaction

A

grind/screen/sieve

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34
Q

describe the process of roller compaction (dry granulation)

A

thin powder sheets formed, milled, passed through screen to reduce size

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35
Q

describe the process of slugging (dry granulation)

A

dry powder blend formed into big tablet, milled to reduce PS, sieved to form individual tabs

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36
Q

in both RC and slugging, the final step it milling and sieving to form granules/ individual tabs but for each, what is milled/sieved?

A

RC: compacts (flakes)
slugging: slugs (big tabs)

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37
Q

whys dry gran preferred?

A

water can interact w drug and excipients

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38
Q

2 examples of filler as excipient used in dry gran?

A

anhydrous lactose: recompaction possible

MCC for RC

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39
Q

examples of a (dry) binder used in dry gran?

A

pregelatnised starch
cross linked PVP..
…

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40
Q

what excipient added to powder blend in melt granulation and give 3 examples?

A

hot-melt BINDER.

  • semi-solid hydrophilic polymer
  • solif hydrophilic polymer
  • hydrophobic wax
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41
Q

when is binder added in melt granulation?

A

added ot powder blend (drug+excips)

at room temp: melted in process/ melted before addition then sprayed onto powder

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42
Q

role of binder in melt granulation?

i.e. process of melt granulation, how do the granules form

A

coats individual granules, promoted aggregation through coalescence

prep cools, liquid bridges -> solid bridges (of binder), grnaules form

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43
Q

3 stages in manufacture of compressed tabs?

A

die filling
compression+compaction
tablet ejection

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44
Q

at what stage of tablet formation(1/3) are flow properties crucial?

A
  1. die filling

die cavities filled by VOLUME by shopper shoe when posiitoned over die

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45
Q

what does volume of powder filled into die during manufacture depend on?

A

heigh of die cavity
diameter of hole
flow properties
… in turn depends on position of lower punch

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46
Q

what of the 3 stages of tab manufacture impact on tab appearance?

A
  1. compression and compaction
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47
Q

2 types of press used in manufacture of compressed tabs?

A

single punch press

rotary press

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48
Q

what does tablet appearance depend on (during manufacture)?

A 
shape of die: oval, circ, oblong
distance between punches
configuration of punch tips:
- flat/convex+bevelled edges
score marks
markings:debossed/ embossed
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49
Q

Manufacture of moulded tablets how are they prepared?

A

by moulding rather than compression in a tablet press

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50
Q

Manufacture of moulded tablets

1 ad and 1 disad?

A

(+) very soft and disintegrate quickly

(-) small in size, limiting their use to drugs active at low doses

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51
Q

the 3 steps in Manufacture of moulded tablets

A
  1. drug mixed with a diluent
  2. A liquid is added to the powder to wet the powder and allow moulding- alcohol-water mixtures are commonly used for that purpose
  3. Tablet generated after evaporation under vacuum
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52
Q

considerations/ preferred diluent to be use din moulded tabs manufacture?
4 examples

and what to check for?

A

Water-soluble diluent
(e.g. lactose, dextrose, sucrose, mannitol)

Lactose + 10-20% sucrose allows the manufacture of tablets with good mechanical strength

Check for incompatibilites of the drug with sugars

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53
Q

moulded tablets example

A

glyceryl trinitrate sublingual tablets

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54
Q

Manufacture of lyophilised tablets

4 steps in process?

A
  1. drug mixed w gelatin and sugar(s)
  2. filling of blister
  3. freezing
  4. freeze drying and sealing
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55
Q

whats characteristic about lyophilised tablets?

A

rapidly disintegrating.

fall apart quick in small amount water

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56
Q

2 ads of lyophilised tablets?

A

(+) fast disintegration

(+) suitable for patients with difficulty swallowing

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57
Q

2 disads of lyophilised tablets?

A

(-) taste and feel may be an issue (organoleptic properties)

-) tablets are soft and will break if forced through the blister (need to peel the seal

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58
Q

lyophilised tabs manufacture: whys dru mixed with gelatin in step 1?

A

affects disoslution profile and how quickly they fall apart

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59
Q

lyophilised tabs manufacture: what ‘sugar(s)’ may the drug be mixed with in step 1?

A

mannitol

to help dissolution process further, and organoleptic properties

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60
Q

what does step 3 of lyophilised tabs manufacture: freezing rate affect?

A

size of ice crystals thus pores in tablet

want strong enough to not break apart but poroud enough so water can enter and disintegrate quick

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61
Q

purpose of freeze drying in almost final step of lyophilised tabs?

A

remove moisture (drying). allw ater removes, pores where ice crystals were

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62
Q

where can disintegration of lyophilised tabs occur?

A

porous so anywhere w small amount water

  • saliva in mouth
  • on tongue- v quick so organoleptic prop important!
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63
Q

Section 2. Formulation of compressed tablets

basic set up for a tablet press has? (2)

A
  • Two punches (cyclinder)
    will come into the die during the compression/compaction to form the tablet
  • One die (flatter circle)
    contains a cavity that will be filled with the powder/granule formulation
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64
Q

3 main types of tablet presses?

A
  • Single-punch press (eccentric press)
    R&D
    Low output (130-200 tablet per minute)
  • Rotary press
    10,000 tabs/minute
    Large scale production
  • Compaction simulator
    for optimisation of compression settings
    Predict potential compression issues
    Mimic production process
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65
Q

What excipients help the tabletting process stage 1: Die filling?

role and when added?

A

powder properties as filled w gravitational flow, so how to improve powder flow:

  • glidants: decrease cohesion, added before compression
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66
Q

Talc (1-2%)
Colloidal silicon dioxide (0.2%)
Starch
Magnesium stearate (<1%)

are all examples of XXX added during die filling, just before compression

A

glidants

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67
Q

Talc (1-2%) is a glidant, what does it also work as and impact on?

A

Also works as an antiadherent

Hydrophobic, impact on wetting/dissolution

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68
Q

how does Colloidal silicon dioxide (0.2%) work as a glidant?

A

Efficient glidant
Small spherical particles (10 nm)
Particles “glide” over each other under pressure
Can be hydrophilic or hydrophobic

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69
Q

Starch is commonly used as what 2 types of excipient?

A

Large quantities may be required
Can also help disintegration
Commonly used as a binder or diluent

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70
Q

Magnesium stearate (<1%) is a glidant, also used as?

A

Commonly used as a lubricant

Can promote flow at low concentrations

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71
Q

what excipient added during b) Compression and compaction stage of tabletting process and why?

A

binder (adhesive)

help promote the formation of interparticular bonds. (gran)

Binders tends to be ductile (undergo plastic deformation) this will be important for the compression process).

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72
Q

how can binder be added for For tablets prepared by direct compression? as in what form?

2 examples

A

as a dry powder (e.g. microcrystalline cellulose, PVP), although binders may be more effective when added as solutions during granulation.

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73
Q

3 examples of types of binders (adhesives) to add during Compression and compaction?

A
  • Starch (5-25%), Sucrose, Gelatin, Gums
  • Polyvinylpyrrolidone (PVP) (2-8%)
  • Cellulose derivatives: HPMC (2-8%), Methylcellulose (1-5%)
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74
Q

What other excipients affect compression-compaction? (3)

and role of each

A

Glidants: help during initial phases of compression (particle re-arrangement)

Lubricants: lower friction between powder+die wall.

Antiadherents: prevent adhesion (sticking/picking) of powder/ granules to die wall/punch tips, especially if the tips bear markings.

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75
Q

As covered in week 1, XXX can promote adhesive forces and make the powder stick to the punches.

A

a high moisture content

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76
Q

2 Examples of antiadherents

A

talc, starch

magnesium stearate

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77
Q

What excipients help the tabletting process step C) Tablet ejection?

A

lubricants reduce friction

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78
Q

consequence of not having lubricant during tablet ejection/ if friction is high?

A

tablets may fracture during the ejection process (capping or fragmentation).

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79
Q

whats the 2 types of Mechanism of action for lubricants?

A 
Fluid lubrication(die-wall lubricants)
Boundary lubrication
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80
Q

describe fluid lubrication (die-wall lubricants)

mechanism of action of lubricants,1
give example

A
  • Formation of a fluid layer between solid surfaces
  • Minimise friction between tablet and die wall during ejection
  • Not used for tablet formulation

Examples: mineral/vegetable oil
Can make tablet surface tacky and mottled

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81
Q

describe Boundary lubrication

mechanism of action of lubricants,2

A
  • Solid surfaces separated by a thin film of the solid lubricant
  • Tends to be fine particulate solids
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82
Q

give the 2 most effective agents in boundary lubrication.

A

Most effective agents (<1%):
Stearic acid
Stearic acid salts
Magensium stearate

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83
Q

downside of using lubricants in:
tabletting process step C) Tablet ejection
and how to overcome these

(2)

A

can interfere with:

bonding during compression-compaction
- impact of lubricant on tablet strength can be assessed

dissolution due to hydrophobicity

  • use hydrophilic (but less effective) lubricants e.g. polyethylene glycol
  • added after disintegrant to avoid generating lubricant-coated disintegrant praticles
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84
Q

3 types of lubricants.

i.e. what 2 excipients are covered by the general term?

A 
all excipients that 
improve flow (glidants), 
decrease friction (lubricants) or 
decrease adhesion (anti-adherents).
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85
Q

What do we need to consider for tablet formulation?(2)

A

Optimisation in terms of the manufacturing process (technical feasibility)
AND
performance (bioavailability).

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86
Q

tablets can be manufactured by… processes? (2)

A

direct compression of a powder blend

compression of granules (to which extra-granular excipients were added).

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87
Q

role of glidants (how do they improve flow)

A

decrease cohesive forces

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88
Q

4 common glidants

A

talc 1-2%
colloidal silicon dioxide 0.2%
starch
mg stearate <1%

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89
Q

starch is commonly used as?(2)

A

binder/diluent

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90
Q

Magnesium stearate is commonly used as….

and when will it promote flow?

A

lubricant.

can promote flow at LOW CONCS

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91
Q

role of diluent/filler in tablets?

A

If drug content is low, diluent/filler determines properties of the powder formulation.

help bulk up powder volume to ease processing and handling.

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92
Q

Ideally, the diluent should have what 5 properties?

A 
Inert
Hydrophilic
Non-hygroscopic
Biocompatible
Cost effective

filler should also have good flow properties (especially for direct compression) and good compactability

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93
Q

what are the 6 issues/tests of tablet manufacture?

A 
uniformity of weight
"" content
mechanical strength
capping/lamination
adhesion to punch
friction during ejection
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94
Q

4 examples of diluent/filler?

A

lactose
sucrose
glucose
MCC

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95
Q

how is diluent/ filler selected?

A

depends on:
processing method (direct compression)
plasticity of other materials in fomrulation (brittle/plastic)

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96
Q

what diluent properties are needed for

a) direct compression
b) brittle material
c) plastic material

A

a) good flow and compactibilty
b) plastic
c) brittle

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97
Q

why does diluent need good flow and compactibilty for direct compression?

A

as no gran step.

if did have that, gran would also affect flow and so will other excips

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98
Q

6 examples of diluents

A 
spray dried lactose
anhydrous lactose
dextrates
starch
dicalcium phosphate
MCC
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99
Q

what 3 diluents have best flowability?

A

spray dried lactose
dextrates
dicalcium phosphate

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100
Q

what diluent has best lubricity?

A

MCC

then starch

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101
Q

what diluent has the best hygroscopicity?

A

anhydrous lactose

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102
Q

what 3 diluents have best solubiliity?

A

dextrates

spray dried lactose
anhydrous lactose

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103
Q

what 2 diluents have best compactabil?

A

dextrates

MCC

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104
Q

what 2 diluents have good disintegration?

A

anhydrous lactose

starch

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105
Q

whats important to remember when choosing excipients?

6 considerations

A

compatible with drug formulating

flowability
lubricity: cohesion,adhesion
hygroscopicity
solubility in water
compactibility
disintegration: break apart to release drug
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106
Q

direct compression/ compaction: how quick is the process?

A

fast as no granulation. only 3 steps

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107
Q

what steps are in direct compression/ compaction?

A

PSR
mixing
tablet press

(no granulation!)

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108
Q

in direct C/C, what is required that may increase production costs but will give the powder the right properties to allow the manufacture of quality tablets?

A

Specific excipients

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109
Q

Direct compression possible issue?

A

increased risk of segregation caused by wide size distribution/ large PS

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110
Q

manufacture of compressed tabs: direct compression/ compaction is good for..?

A
  • rel soluble drugs with good compactibility

- potent drugs

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111
Q

why is direct compression/ compaction good? benefit of manufacture of compressed tabs?

A

might get faster disintegration and drug dissolution as

tablet –> fine powder particles

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112
Q

why wouldnt you add certain excipients (LUBRICANT) before tabletting process? (compressed tabs)

A

may coat other excipients and alter efficacy of disintegrant.

mixing time too long: lubricant may affect strength of whole prep- add late as possible and as close to tabs process as possible

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113
Q

Compression vs compaction

difference?

A

Compression = reduction of bulk volume under applied force

Compaction = formation of a solid with defined geometry and strength. Here, compaction allows the tablet to be formed.

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114
Q

3 stages of compression and compaction?

what will powder blend/ granules go through?

A

re-arrangement
deformation
bonding

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115
Q

what do all of the 3 stages of comp/comp ultimately do? role?

A

decrease bulk vol significantly instead of die cavity, form tabs to be ejected

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116
Q

what happens in step 1. re-arrangement of C/C?

A

powders parts/ granules re organised under applied force

low pressure: parts organise in bed = bulk vol, porosity decrease, particle packing change

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117
Q

what does packing of particles depend on? (2)

A

shape
size distribution

wide size dist = possibility smaller parts through void = decrease in porosity (sometimes seen at compression low pressure)

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118
Q

in C/C, cant always fully rely on reorganisation of powder parts, how can deformataion instead be triggered?

A

through applying pressure

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119
Q

what type of bonds produced in finall stage of C/C?

A

interparticular bonds through parts coming close…

generation of tablets

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120
Q

4 substages of deformation (step 2 in C/C)?

A

deformation
densification
fragmentation
attrition

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121
Q

3 types of deformation?

A

elastic
plastic
fragmentation

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122
Q

5 things yield point is affected by

A 
polymorphism
salt form
moisture content
particle size
compression rate
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123
Q

whats yield stress on strain/stress graph?

A

when region of elastic deformation changes to plastic

from elastic to plastic

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124
Q

whats the difference in elastic/ plastic change (deformation)?

in terms of cohesion?

A

elastic: pressure removed, parts return to shape, cohesive forces formed during compression lost
plastic: permanent. if pressure removed, parts dont return. cohesive forces formed in process retained

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125
Q

when will fragmentation occur in powders during deformation (and not elastic/plastic deformation)?

how will they behave?(same/diff)

A

if compressed further.
particle breaks down, smaller parts formed

fragments have diff behaviour!

will still have some big parts- undergo fragmentation

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126
Q

how are fragments formed during deformation different to the powder?

A

smaller, can sift through void spaces
change packing
new surface created: undergo fragment again:
deformation undergo: plastic/elastic

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127
Q

Granules I: what can compression lead to for granules?(2)

A

changes in physical properties of the PRIMARY POWDER PARTS/ GRANULES

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128
Q

what happens during compression of granules will depend on what 2 factors?

A

properties of primary particles/ granules

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129
Q

what 2 changes can occur to granules during compression? processes

A

rearrangement: limited impact for grans
deformation: elastic/plastic densification

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130
Q

whats consequence of mainly dealing with coarse particles, during compression?

A

limited possibiliities for rearrangement inside a granule bed

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131
Q

how do powder parts change during compression? i.e. what changes?

A

change in INTRA-granular porosity.

initially spread out, come closer and pores close

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132
Q

fragmentation possible during deformation but not as common as..?
describe this phenomenon

A

attrition/erosion-

fragment removal from granule surface through granules colliding w each other/ walls of cavity/ friction.

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133
Q

attrition/erosion more likely if?

A

granules have a rough surface

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134
Q

what 2 things can be used to assess compressibility?

A

looking at:

  • properties of ejected tabs
  • compression/decompression events
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135
Q

how can looking at properties of ejected tabs be used to assess compressibility?(2)

A
  • scanning electron microscopy: study fragmentation and deformation
  • size+size dist of deaggregated tabs
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136
Q

how can looking at compression/decompression events be used to assess compressibility? (3, ‘vs’)

A

tab volume vs upper punch pressure
tab porosity vs upper punch pressure
upper punch pressure vs lower punch pressure

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137
Q

what does tablet (mechanical) strength depend on and what is this promoted by?

A

inter-particular bonding (the number and strength of the bonds), promoted by compression

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138
Q

what does bonding mainly result from for dry powders? (3)

A

solid bridges
adsorption bonding
mechanical interlocking

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139
Q

what is solid bridges?

powder deformation- bonding

A

mixing at interface between solid, forming a continuous solid phase

140
Q

solid bridges: what type of tabs (3) is it most likely for?

powder deformation- bonding

A

tabs with

  • amorphous/MP ingredients present
  • low porosity
  • made form granules in presence of binder
141
Q

adsorption bonding is bonding as a result of what?

powder deformation bonding

A

reduced inter particular distances

142
Q

adsorption bonding more likely
for tabs made from granules in presence of binder, including (3) bonds?

(powder deformation bonding)

A

binder-binder bonds
binder-substrate bonds (drug+excip)
substrate-substrate bonds

main mechanism for tabs with 5-30% porosity

143
Q

whats mechanical interlocking?

powder deformation bonding

A

interparticular locking of irregularly shaped rough particles

144
Q

high compactibility leads to tablets with..(2)?

A

good resistance to fracture

low tendency to cap/laminate

145
Q

what cap/laminate and what tabs is it most liekly in?

A

capping: partial/total fracture of top/bottom layer in tab
lamination: separation of tabs into layers

likely if tabs have poor compactibilty

146
Q

how is compactibility measured? what test

whats measures and units

A

hardness test: tensile fracture (kg) measured

147
Q

how does compression affect compactibility for solid particles? (3)

A

fragm+ plastic deformation associated to increased tab strength
elastic deformation: - impact
impact of size

148
Q

how does fragmentation help solid particles compactibility? (C and C)

A

formation of smaller parts + decreased porosity

149
Q

how does plastic deformation help solid particles compactibility? (C and C)

A

increase area of contact between partcs

150
Q

why does elastic deofrmation have neg impact on solid particles compactibility? (C and C)

A

low tablet strength

higher capping/lamination propensity

151
Q

impact of size: smaller particles thought to lead to XXX tablet strength (but might be more relevant for micronised powders

more studies needed

A

Increased

152
Q

how does compression affect compactibility for granules? (4)

A

impact of props of primary powder parts
impact of granulation process on granule (shape,size,por,strength)
imp on granule composition
presence of binder

153
Q

what may binders help (2) for granules in C/C?

A 
granule deformation (increased)
bond strength
154
Q

Reduction in bulk volume (i.e. COMPRESSION) can be obtained through (3)?

and how does pressure compare in each process

A

Re-arrangement - LOW pressure

Deformation/ densification - MODERATE pressure

Fragmentation - HIGH pressure
creates new surfaces that may behave differently

155
Q

The compression phase is followed by COMPACTION, where inter-particular bonds are created that will allow….

A

formation of the final tablet with acceptable mechanical strength.

156
Q

why must Care be taken not to “over-compress” tablets? 2 processes/points

A

can lead to the fracture of the tablet through capping or lamination.

157
Q

The compressibility of a material can be measured by (2)

A

Testing the resulting tablets

Testing compression/decompression events

158
Q

The compactability of a formulation can be measured by

A

Testing tablet hardness

159
Q

what can have an impact on the efficacy of the compaction phase.? (2)

A
  • Events that occur during compression phase (re-arrangement, deformation)
  • properties of the materials
    This includes the impact of the binder.

Also, it should now be easier for you to see which lubricants can affect tablet strength! Hint: think about how lubricants (incl. glidants and anti-adherents work and why we use them!)

160
Q

what is the definition of an excipient?

A

any substance other than active drug/ prodrug which has been appropriately evaluated for saftey and is included in drug delivery system

161
Q

4 possible roles of excipient?

A
  • aid processing of system during manufac
  • protect, support or enhance stability, bioavailability or patient acceptability,
  • assist in product identification
  • enhance any other attribute of overall safety + effectiveness of drug product during storage / use
162
Q

9 essential properties of a good tablet?

A
  1. acceptable to the patient
  2. contain right drug +drug content
  3. pleasing appearance: no cracks, chips, mottling, etc.
  4. consistent weight, size, shape, general appearance
  5. release drug in reproducible and predictable manner
  6. good chemical, physical and microbiological stability
  7. suitable packaging: to maintain integrity through lifetime
  8. strength: keep shape during manufacture, processing, packaging, shipping and use
  9. exempt of toxicity causing excipients/ contaminants
163
Q

Why is tablet testing required?

and where are tablet tests found?

A

ensure the quality of the final product.

Some tests are described in the BP (both in general and specific monographs), while others are not.

164
Q

name of Tests that are not described in the BP?

A

non-phamacopoeial or non-compendial tests, but still provide useful information on tablet quality.

165
Q

Problems during the manufacturing process can lead to issues in ..(3)?

give examples of each problem

A

content uniformity
e.g. issues during mixing

uniformity of weight
e.g. issue with flow

changes in appearance
e.g. capping, lamination, chipping

166
Q

7 tests typically performed on tablets?

A 
Appearance
Thickness and diameter
Uniformity of weight
Uniformity of content
Hardness and friability
Disintegration
Dissolution
167
Q

how are tablets tested for appearance?

A

ensure they are devoid of cracks, chipped edges and that colour is uniform.

168
Q

Information on tablet thickness and diameter will be useful when?

A

during packaging.

169
Q

At fixed compression forces, tablet thickness will depend on (4)?

A

Die filling
Tablet weight
Particle size and distribution
Packing during compression

170
Q

Tablet thickness and diameter:

what will tablet thickness depend on if the die fill volume is fixed?

A

compression force

171
Q

hows tablet thickness measured? name of equipment

and what range should it be within?

A

calipers

variation should not exceed 5% of the mean thickness.

172
Q

what will tablet diameter be affected by?

A

the configuration of the die cavity and punches.

173
Q

suitable range for tablet diameter test?

A

Diameter can vary by

3% for tablets with a diameter 12.5 mm and above
5% for tablets with a diameter less than 12.5 mm

174
Q

Uniformity of dosage form is a pharmacopoeial test used for what 2 types?

A

uniformity of:

  • weight/mass
  • content
175
Q

The test used for uniformity of dosage form will depend on ? (2)

A

the drug content and tablet type

176
Q

difference between the two types of uniformity of dosage form tests in terms of what tablets they can do?

A

Uniformity of mass:

  • uncoated
  • film coated tabs

Uniformity of content: all other tabs

177
Q

uniformity of weight/mass is linked to?(2)

A

powder flow and uniform die cavity filling

178
Q

Excessive variation in uniformity of weight/mass test is linked to issues with? (3)

A
  • Formulation
  • Process development
  • Equipment maintenance
179
Q

hows uniformity of content test done?

A

Analytical method and use calibration curve

UV, HPLC, spectrometry

180
Q

For uniformity of weight, the deviation allowed depends on what?

A

average mass of the tablet

IF API content is
• ≥ 25 mg or
• contributes to ≥ 25 wt%

181
Q

Pass/fail specification can be found in the BP under what for:

a) new products
b) commercialised dosage forms

A

a) the general tablet monograph- for new products

b) the product monograph- for commercialised dosage forms

182
Q

tablet testing: mechanical strength/hardness- how is it done?

A

(Not a pharmacopoeial test)

Diametral crushing is the most common test
Hardness= force required to break a tablet

183
Q

problems with tablet being

a) too hard
b) too soft?

A

a) may not disintegrate.

b) will not sustain further processing, including coating/ shipping.

184
Q

what type of method is friability?

and what does it measure?

A

Attrition method- measures tendency to powder, chip or fragment during handling

185
Q

how is friability test done and what should mass loss not exceed?

A

Pre-weighted tablets are placed in a friabilator, dropped and rotated
Mass loss should not exceed 1%

186
Q

What is disintegration?

A

break-down of a compressed tablets into smaller fragments after administration.

187
Q

Disintegration requires?

in terms of force

A

destruction of bonds formed during compaction process.

I.e. need a force strong enough generated that overcomes the inter-particular forces keeping the tablet together.

188
Q

Why is disintegration important for tablets?

A

Tablets that are manufactured by compression, need to break-down in order for the drug to be released and absorbed.

189
Q

How do disintegrants work? (3)

A

work by

  • Enabling water entry (wicking)
  • Swelling
  • Releasing gaseous materials
190
Q

what is meant by 3rd step of disintegrants - work by ‘Releasing gaseous materials’?

A

acid-base reaction = release of CO2

this is the mechanism through which effervescent tablets will disintegrate

191
Q

why do we need strict control of the environment during tabletting for effervescent tabs for example?

A

Releasing gaseous materials
acid-base reaction = release of CO2

strict control of the environment required during tabletting for these humidity-sensitive formulation

192
Q

3 steps of tab disintegration

A

tablet wetted
fluid enters pores
tab disintegrates

193
Q

disintegration mechanism 1: wicking (water entry) efficacy depends on what 4 factors?

A
  • Wettability: Surfactants
  • Pore size distribution
  • Disintegrant addition: intra vs extragranular
  • Compression force
194
Q

most disintegrants work through what mechanism?

and what impact this

A

swelling

impact of porosity

195
Q

in regard to grnaulation, when are the following disintegrants added?

  • Intragranular:
  • Extragranular:
  • Combination:
A
  • Intragranular: Before granulation
  • Extragranular: After granulation
  • Combination: Both before/after :)
196
Q

for optimum performance, what % of disintegrants are extragranular?

A

20-50% of extragranular
disintegrant
added After granulation

197
Q

what disintegrants aid disintegration of tablet in aq media -> granules?

A

extra-gran

198
Q

what disintegrants aid disintegration of granules -> fine partcs?

A

intra grnaular

199
Q

drug in what state will have slowest-> fastest rate od dissolution?

A

slow: tab in aq media
moderate: granules
fast: fine partcs (high SA)

then goes into bloodstream

200
Q

benefit of not having middle/ extragran/ granules step in disintegration?

A

tab in aq media –> fine partcs.

break down directly, faster :)

201
Q

what affects dissolution rate?

and how does this impact granule dissolution

A

size and SA

granules bigger = slow drug release rate smaller SA

202
Q

physicochemical properties to consider in disintegration? (3)

A
  • Small particle size = high SA
  • Hygroscopic material (water penetration imp, consider in moisture sensitive drugs!)
  • Gas-liberating (effervescent tablets) CO2 release
203
Q

example of Conventional disintegrant and how does it work?

A 
Starch (potato, corn)
• Up to 10% in formulation
Works by 
• wicking/swelling
• particle-particle repulsion
204
Q

2 examples of Superdisintegrants and how do they work?

A
  • Modified starch
  • Modified cellulose
  • Work be swelling +++++++
  • Hygroscopicity +++++
205
Q

how do Conventional disintegrant and Superdisintegrant compare?

(in terms of conc needed)

A

Conventional disintegrant
• Up to 10% in formulation

Superdisintegrant
• Effective at low conc (1-5%)
• more hygroscopic

206
Q

5 possible Disintegrants and which 2 provide rapid swelling?

A

Starch
Microcrystalline cellulose
Crospovidone

Rapid swelling:
Sodium starch glycolate
Croscarmellose

207
Q

what is Dissolution testing used to determine?
and whats the target range

(diff process to disintegration)

A

Determination of drug release rate
• Linked to in vivo performance
• Target for IR: >80-85% drug release within 30 min

208
Q

in disintegration test. how does range compare for:

a) Conventional tablets
b) Sublingual tablets-

A
  • Conventional tablets- disintegration within 5-30 min

* Sublingual tablets- 3 min

209
Q

disintegration test Performance affected by (3)?

A
  • Disintegration media used
  • Temperature during the test
  • Formulation factors
210
Q

what factors affect dissolution test and therefore must be standardized? (3)

A

Factors affecting drug solubility
• Composition, pH, temperature of dissolution medium
• Agitation speed

Factors affecting dissolution
• Conc of dissolved substances: Sink vs non-sink conditions
• Fluid flow inside diss chamber
• Choice of apparatuses

Factors affecting quantification
• Analytical method choice

211
Q

Factors affecting

disintegration/dissolution (5)

A

•Solubility/hygroscopicity of powder formulation
•Type + quantity of disintegrant
•Type + quantity of binder
•Adding lubricant
•Manufacture process
- Granulation- How compact were the granules?
- Mixing- adding lubricants/ antiadherents
- Compression- what force used?

212
Q

generally: how does quantity of disintegrant used affect Disintegration time?

A

higher quantity = lower Disintegration time

213
Q

generally: how does Compression force used affect Disintegration time?

A

higher force (after trough) = higher Disintegration time

214
Q

what is likely the rate-limiting step and why?
(Factors affecting
disintegration/dissolution)

A

Dissolution because drug needs to be in solution to be absorbed

215
Q

Dissolution rates for BCS II drugs can be improved by? (4)

A
  • Using polymorph, salt, amorphous form
  • PSR: must account for impact on flowability and cohesion!
  • Using a matrix former
  • E.g. water-soluble polymer like polyethylene glycol / lipid
  • Drug dissolved/ finely suspended in matrix

• Using a dissolution enhancer

216
Q

whats the first step in tablet disintegration

A

Water penetration

217
Q

describe: disintegrants can work either by… (2)?

A

wicking- facilitation penetration of water/fluids within the solid mass

swelling- increase in particle size induce by water-/fluid absorption

218
Q

What are the main differences between glidants, antiadherents and lubricants?

A

Glidants: improve powder flow. work by decreasing cohesive forces, added just before compression.

Lubricants: lower friction between powder + die wall.

Antiadherents: prevent adhesion (sticking or picking) of powder/ granules to the die wall or punch tips, especially if the tips bear markings.

219
Q

Which excipients will have the most influence on powder flow during die filling?

A

glidant

220
Q

TRUE or FALSE, the choice of diluent can affect powder flow? Justify your answer

A

This will definitely be true for direct compression.

221
Q

2 main advantages of direct compression?

A

Faster disintegration and drug dissolution.

222
Q

4 reasons for using granulation in tablet manufacture

A

To improve flow properties

To improve mixing quality

To improve compactability

To optimise dissolution process

223
Q

How can spray-dried granules improve the compactability of a powder?

A

By changing the properties of the material (e.g. increasing ductility).

224
Q

What excipients MUST be added to the powder before granulations? Briefly justify your answer

A

Diluent/filler and binder + some of the disintegrant.

225
Q

What excipients MUST be added to the dried granules before compression? Briefly justify your answer

A

Lubricants, at least some of the disintegrant, glidant if needed.

226
Q

TRUE or FALSE, binders are added during the wet granulation process ONLY. Briefly justify your answer

A

Binders are also added for dry granulation and direct compression

227
Q

Why is ductility important for a binder during the compression/compaction process?

A

Ductile material undergo a significant amount of plastic deformation before breaking. Plastic deformation is permanent, even when the stress is removed. Plastic deformation can lead to stronger tablets.

228
Q

Why is direct compression better suited to the formulation of potent drugs?

A

Excipients will be the main component of the powder formulation. This will allow selection of excipients with the right properties for direct compression.

229
Q

TRUE or FALSE elastic deformation increases the risk of lamination

A

Risk of lamination as stress is removed due to relaxation and attempt to return to the original shape.

230
Q

bonds involved in the formation of a tablet (3)

A

Solid bridges

Adsorption bonding

Mechanical Interlocking

231
Q

What are chewable tablets? (4)

where does disintegration, drug dissolution happen?

A
  • usually compressed tabs
  • disintegrate in the mouth with/ without chewing
  • no water needed-easier to swallow
  • intended for drug absorption in GI
    (where dissolution happens)
232
Q

Who are chewable tablets useful for?

A
  • Paediatric patients
  • Vet use: excipient safety should be confirmed, flavouring tailored
  • Adult patients with swallowing difficulties
233
Q

Why don’t chewable tablets typically contain disintegrants?

A

chewing causes disintegration

234
Q

What excipient is included and preferred in chewable tablet formulation?

A

Diluents: sorbitol, mannitol preferred; can act as sweeteners

235
Q

What properties need careful consideration with chewable tablets?

A

Organoleptic properties:

Texture, mouthfeel, taste, aftertaste

236
Q

Chewable tablets have the same criteria as conventional _ tablets in terms of f_, c_, ad_/fr_, etc.

A

Same criteria as conventional compressed tablets in terms of flow, compactability, adhesion/friction, etc.

237
Q

For chewable tablets, hardness adjusted to prevent what while chewing? (3)

A
  • Damage to teeth
  • Damage to dentures
  • Pain to mandibular joints
238
Q

Name 4 examples of chewable tablets that aren’t vitamins.

A

Raltegravir
Atorvastatin
Montelukast
Sildenafil

239
Q

What are oromucosal tablets?

A

Tablets that disintegrate in the oral cavity and are dissolved and absorbed here too

240
Q

What are 2 categories of oromucosal tablets?

A
  • Buccal + sublingual tablets

- Compressed lozenges

241
Q

What are the characteristics of buccal + sublingual tablets and why are they useful?

A
  • Smaller + more porous = enable disintegration in oral cavity and small volume of fluid
  • Small size also reduces patient discomfort, esp w mucoadhesive preparations needing to take in place for 1-2 hours
242
Q

What excipient is excluded from compressed lozenges?

A

disintegrants

similar composition to compressed tabs

243
Q

How do compressed lozenges behave? (dissolution)

A

Dissolve slowly in mouth, release some of drug into saliva

244
Q

Why type of diluents/binders are pressed w compressed lozenges?
example

A

Water-soluble diluents + binders w nice taste should be preferred e.g. dextrates

245
Q

What forces used to prepare compressed lozenges - what do they limit but increase?

A

high compression forces, which limit porosity but increase mechanical strength

246
Q

What specifications should oro-mucosal tablets meet?

and wb buccal+sublingual specifically?

A

follow the definition of tablets, in accordance with the BP.

Buccal + sublingual tabs: of suitable mechanical strength to allow processing and handling without breaking down.

247
Q

What are multiple compression tablets and why are they useful (3)?

A

Tablets made from successive compression cycles, offering the means to:

  • Separate 2+ incompatible APIs
  • Allow APIs to be mixed at diff rates
  • Address mixing issues where uniform distribution of APIs cannot be guaranteed
248
Q

What are the 3 configurations of multiple compression tablets?

A

(A) 2 API-containing layers separated by a drug-free layer to keep APIs separated (sandwich)

(B) Two API-containing layers with each layer providing different release profiles, for example (empty sandwich)

(C) Tablet-in-a-tablet

249
Q

How are multiple compression configuration B tablets prepared? empty sandwich

A

first powder is compacted by compression, then 2nd (and/or 3rd) added to die and compressed

250
Q

How are multiple compression configuration C tablets prepared? (3)

Tablets-in-tablet

A

compression coating

  • Core tablet made 1st, then moved to slightly larger die which contains 2nd powder as coating
  • Interface created between 2 powders = stability issues w incompatibility cases
251
Q

What are orodispersible tablets (ODTs)?

and how quick do they break down

A
  • Quickly disintegrating/dissolving tablets

- Breakdown within 3 minutes, often through seconds before being swallowed

252
Q

Why are orodispersible tablets useful in paediatric/geriatric patients and patients with dysphagia?

A

no liquid is required

253
Q

What are the advantages of orodispersible tablets? (4)

A
  • Quick drug release
  • Good patient acceptability
  • Convenient
  • Improved bioavailability IF buccal absorption
254
Q

What are the disadvantages of orodispersible tablets? (4)

A

× High hygroscopicity
× Low mechanical strength
× Taste masking required
× Stability issues

255
Q

What are 4 processes that can be used to be prepare orodispersible tablets?

A

moulding
spray-drying
compression/compaction
lyophilisation

256
Q

What 3 excipients are used in orodispersible tablets?

A
  • Rapidly dispersing/dissolving fillers
  • Flavouring/sweetening agents
  • Superdisintegrants
257
Q

What 2 quality tests are performed on orodispersible tablets and what do they tell us?

(W_ T_ and M_ U_ T_)

A
  • Wetting time – related to porosity + hydrophilicity; shorter wetting time = faster disintegration
  • Moisture-uptake test – information on the stability of the tablets when exposed to humidity
258
Q

What are scored tablets?

role of score?

A

Compressed tablets manufactured with a score or scoring lines to facilitate tablet splitting

259
Q

What can scoring tablets affect about its properties? (3)

A
  • uniformity of dosing, if API not homogeneously distributed throughout tab
  • disintegration/ dissolution of drug from tablet fragments
  • stability as API + excipients become exposed to environment
260
Q

What authority has a test on the subdivision of scored tablets?

A

The International Pharmacopoeia

261
Q

What is coating?

A

application of an outer layer to the surface of a solid dosage form

262
Q

Why do we coat tablets and other solid dosage forms?

  1. to protect…
  2. to mask…
  3. to make large…
  4. to control where…
  5. to control or sustain…
  6. to standardise…
  7. to allow..
  8. to reduce risk of…
A
  1. To protect the API from light + moisture
  2. To mask a bad taste (e.g. bitter taste)
  3. To make large tablets/capsules easier to swallow
  4. To control where the drug is released (e.g. enteric coating)
  5. To control or sustain drug release
  6. To standardise appearance and aid branding
  7. To allow quick identification of a product
  8. To reduce the risk of dusting and contamination
263
Q

What are 4 types of coating?

A
  • Sugar coating
  • Film coating
  • Spray coating
  • Compression coating
264
Q

What is sugar coating?

A

traditional coating method also used for candy; limited to tablets in drug formulation

265
Q

What are the advantages of sugar coating? (5)

A
  • Low upfront material cost
  • Fairly simple process
  • Visually pleasing tablet appearance
  • Taste masking
  • Makes tablets easier to swallow
266
Q

What are the disadvantages of sugar coating?

A
  • Trained personnel needed
  • Multiple steps needed
  • Time consuming
  • Harder to add markings on the tablet
  • Increases tablet weight and size
  • Intra- and inter-batch variability
267
Q

What are the 6 steps of the sugar coating process?

A
  • sealing of tablet cores
  • subcoating
  • smoothing
  • colouring
  • polishing
  • printing
268
Q

What occurs in the 1. sealing of tablet cores step of sugar coating?

A

Tablets are rendered waterproof to:

  • prevent water from penetrating the tablet
  • prevent stability issues

Sealing prevents the core from breaking down during the coating process

269
Q

What are examples of excipients used as 1. sealing coats in sugar coating? (5)

A
  • alcoholic shellac solutions
  • cellulose acetate phthalate
  • polyvinyl acetate phthalate
  • hydroxylpropylcellulose
  • insoluble polymer for enteric coating
270
Q

What occurs in the 2. subcoating step of sugar coating?

A

Subcoating is applied to smooth edges and round off the tablets
• Tablets are dried in between coats
• Tablet weight typically increases by 30-50% at this stage
Requires addition of bulking agents, antiadherents and binders

271
Q

What occurs in the 3. smoothing step of sugar coating?

A
  • Application of a sucrose coating
  • Completes the rounding of the tablet
  • Facilitates the colouring process
272
Q

What occurs in the 4. colouring step in the process of sugar coating?

A

Sucrose and colouring agents are applied

273
Q

What are 2 examples of colouring agents used in sugar coating?

A

Water-soluble dye

Water insoluble pigments

274
Q

What occurs in the 5. polishing step in the process of sugar coating?

A

After colouring, tablets have a dull appearance so it provides glossy finish

275
Q

What are the excipients used in the polishing step of sugar coating?

A

Waxes as fine powders, suspensions/solutions (in an organic solvent)
• beeswax, carnauba wax. candelilla wax

276
Q

What occurs in the 6. printing step in the process of sugar coating?

A

identification and branding

277
Q

What are the excipients used in the 6. printing step of sugar coating?

A

edible inks

278
Q

what 2 stages of sugar coating process do not use excipients?

A

step 2: subcoating

step 3: smoothing

279
Q

Excipients used in Sugar Coating Preparations

A 
sucrose
binders
fillers
colouring agents
antiadherents, lubricants, glidants
flavouring agents
stabilisers
280
Q

role of binders as excipients in sugar coating preps?

A

make coating stronger and more elastic

reduce brittleness

281
Q

examples of binders as excipients in sugar coating preps?

A 
PVP
acacia
gelatin
starch
cellulose
ethers
282
Q

role of fillers as excipients in sugar coating preps?

A

bulk up coating e.g. calcium carbonate

283
Q

role of talc as excipients in sugar coating preps?

A

example of lubricant…

reduce friction between tabs in coating pan

284
Q

2 examples of stabilisers as excipients in sugar coating preps?

A

surfactants

thickening agents

285
Q

why may you need alternatives for sucrose as excipients in sugar coating preps?

A

diabetics, preserve dental health.

50-60%

286
Q

What are 6 common issues w/ sugar coating?

A
  • Chips in the sugar coating
  • Cracks in the sugar coating
  • Coating does not dry
  • Surface not uniform in colour
  • Sweating
  • Marbled colour
287
Q

How can you resolve chips in a sugar coating? (2)

A
  • Ensure enough polymer is added to the coating preparation

* Check fillers used

288
Q

How can you resolve cracks in a sugar coating? (2)

A
  • Apply sealing coat: prevent moisture-induced tablet expansion
  • Wait longer between compression + coating to allow tablet to recover from stress of compression
289
Q

What causes the sugar coating to not dry?

and how to prevent?

A

an excess of invert sugar

  • Avoid heating sucrose under low pH conditions
290
Q

How can you resolve sugar-coated tablet surfaces not being uniform in colour? (3)

A
  • Ensure enough coating is used and that the preparation is mixed well
  • Limit the risk of colour migration during the drying steps
  • Ensure that surface is smooth before applying the coloured coating
291
Q

How can you resolve sugar-coated tablets sweating?

A

Optimise the drying steps to control moisture levels

292
Q

What causes tablets to sweat?

A

excess moisture in coating

293
Q

What causes a marbled colour on sugar-coated tablets?

A

an uneven coating surface

294
Q

How can you resolve sugar-coated tablets being a marbled colour?

A

coating should be smooth before waxes are applied

295
Q

How does film coating compare to sugar coating in terms of duration?

A

quicker needing only 1 step and lasting only 1-2 hours

296
Q

How are tablets film-coated?

A
  • Tablets in pan under constant rotation as polymer solution/dispersion is either sprayed onto tablet, or aerosol used to deliver coating onto tablet surface
  • Tablets then collected and dried to remove solvent used to prepare polymer solution/dispersion
297
Q

What differs about the appearance and weight of film-coated tablets compared to sugar-coating tablets and why?

A
  • edges still visible in film, (in sugar-coated: all edges filled and tablet rounded off)
  • film: duller, sugar: glossing process gives tablet shiny surface
  • film: minimal weight change of 2-3% compared to sugar: 30-50%
298
Q

What are the 2 main types of film coating?

A

immediate release and modified release

299
Q

What are immediate-release film coatings?

A

those with no expected impact on biopharmaceutical properties

300
Q

Are immediate-release film coatings soluble or insoluble?

How do they behave in contact w GI fluids?

A

water-soluble, quickly dissolving in contact w GI fluids

301
Q

What are 3 types of ingredients immediate-release film coatings can be made from?

A
  • cellulose derivatives
  • vinyl derivatives
  • aminoalkyl methacrylates
302
Q

What are the characteristics of cellulose derivatives used in immediate-release film coatings?
(water soluble? good or bad film properties? easy to apply? can it be used with a colouring agent?)

A 
HPMC:
• Water-soluble
• Good film properties, especially mechanical
• Easy to apply to tablets
• can be used+/- colouring agent
303
Q

What are the characteristics of vinyl derivatives used in immediate-release film coatings?
(2 examples? good or bad film properties? barrier to what?)

A
  • Copovidone
  • Polyvinyl alcohol (PVA)
  • Good film properties
  • PVA = good barrier to gases and moisture if excipients sensitive to any of these
304
Q

What are the characteristics of aminoalkyl methacrylates used in immediate-release film coatings?
(soluble at…? organoleptic property? options for coating preparation?)

A
  • Soluble at acidic pH (amine group ionised)
  • Taste-masking

preparation options:
• Organic solution
• Aqueous dispersion

305
Q

What are modified-release film coatings?

A

Delayed or extended release, including gastro-resistant coating

306
Q

Is modified-release coating water soluble/ insoluble and pH dependent?

A

either water-insoluble or its solubility depends on pH (allowing us to have GI resistant coatings)

307
Q

What are the 4 main ingredients that can be used in modified-release film coatings?

A
  • cellulose derivatives
  • methyl methacrylate
  • methacrylic acid copolymers
  • phthalate esters
308
Q

modified release coating: cellulose derivatives

give 1 example

A

ethyl cellulose

309
Q

modified release coating: cellulose derivatives

give 3 properties

A

e. g. ethyl cellulose
- water insoluble
- organic soln
- aq dispersion

310
Q

modified release coating: methyl methacrylate

give 3 properties

A

water insoluble
permeability: extended release
aq dispersions

311
Q

modified release coating: methacrylic acid copolymers

give 3 properties

A

gastroresistant coating
insoluble at low pH
aq dispersions

312
Q

modified release coating: phthalate esters

give 4 properties

A

delayed release
phthalate acid substitution
organ soln
aq dispersions

313
Q

4 parameters to consider in film coating polymers

A

sol
viscosity
permeab
mechanical props

314
Q

what to consider for 1. solubility of film coating polymers?

A

immediate release (water soluble) or modified (water insoluble, pH dependant)?

solvent selection: aq/organic

315
Q

why consider for 2. viscosity of film coating polymers?

A

will affect application of film coating onto tabs

how easy to apply soln/dis[ersion

low= harder to handle

316
Q

what to consider for 3. permeability of film coating polymers?

A

of drug
taste masking
gases
moisture

317
Q

what to consider for 4. mechanical props of film coating polymers?

A

strong
flexible
adhesive

no cracks/ breakage/peeling

318
Q

film coating formulations are polymer + what 4 things?

A

plasticiser
colouring agents
solvents
others

319
Q

role of plasticiser in film coating formulations?

A

reduce brittleness

increase film flexibility

320
Q

plasticiser examples?

A

• Polyethylene or polypropylene
glycol
• Triethyl acetate
• Oils/glycerides

321
Q

examples and role of Colouring agents in film coating formulations?

A

• Water-soluble dyes
mottling

• Water-insoluble 
pigments
Opacity
Coverage
physical Protection from light
322
Q

(organic) Solvents examples in film coating formulations? (3)

A

Volatile

  • Acetone
  • Methanol
  • dichloromethane
323
Q

(organic) Solvents in film coating formulations: Issues with (4)

A
  • Environment
  • Safety
  • Cost
  • Traces- remove so amount left in coating is minimal
324
Q

4 other excips used in film coating formulations

A
  • Surfactants: Spreadability
  • Flavour
  • Sweetener
  • Glossant
325
Q

Quality attributes of film-coated tablets (3)

A

•Uniform coverage and colour
Intra- and inter-batch
•Meet required specifications
•No defects

326
Q

Quality attributes of film-coated tablets: visual?

a) Due to coating process
b) Due to formulation

A

Due to coating process
• Overwetting
• Overdrying

Due to formulation
• Issues with mechanical strength
• Tablet: Breakage and erosion
• Coating: Cracking, chipping, peeling

327
Q

Quality attributes of film-coated tablets: functional?

A

Impact on

Biopharmaceutical properties

328
Q

which type of coating is FASTER? describe

A

Film-coating is much faster vs. sugar-coating

  • Limited increase in weight
  • Polymer film on tablet surface
329
Q

Film-coating can be used for (3)

A

immediate release tablets
- water-soluble polymer coating

immediate release + taste masking
- soluble in acidic pH only

delayed/ extended release

  • water-insoluble coating
  • pH-dependent coating. insoluble at acidic pH
330
Q

Plasticizers can be added to coating why?

A

to optimise mechanical properties

331
Q

Spray coating is also known as ?

A

fluidised bed coating.

332
Q

3 SPRAY COATING METHODS?

A

Top spray
Bottom spray
Tangential spray

333
Q

3 characteristics of Top spray tablet coating?

A

taste masking
gastro resistant coating
barrier films

334
Q

2 characteristics of bottom spray tablet coating?

A

sustained release

gastro resistant coating

335
Q

3 characteristics of tangential spray tablet coating?

A

layered coating
sustained release
gastro resitant coating

336
Q

potential issues with splitting or crushing a tablet

A
  • Stability issues- increased exposure to humidity and air
  • Uniformity of content- impact of nonuniform distribution of API/excipients (mostly an issue if
    part of the tablet will be used)
  • Toxicity and aerosolization of the powder
  • Impact on release/bioavailability
  • Impact on taste

i.e.
Drug instability
Change in pharmacokinetics and bioavailabilit

337
Q

when tablet splitting or crushing may be required…

A
  • Dose adjustment needed: smaller dose required than that present in one whole tablet.
  • Dealing with hard to swallow tablets for elderly patient e.g. Drug contents may need to be mixed with food/drink to make swallowing easier.
338
Q

considerations with tab splitting/crushing

A
  • Sugar/film coating: crushing will make tablets taste unpleasant, and harder to swallow
  • Enteric coating: should never be crushed, used as protection from acid environment, protect the stomach from the drug or deliver the drug to the site of action.
  • Modified release: should never be crushed. If damaged, whole dose can be released too quickly in the body, receive very high dose, side effects likely
339
Q

what 2 types of tab coating = never to be cruhsed?

A

enetric and MR

340
Q

Potential risks: of tab crushing/splitting?

A
  • If product has carcinogenic/teratogenic properties, may expose to health risks by powder aerosolization
  • Products containing hormones (oral contraceptives, HRT) and corticosteroids – similar risks
  • Several drugs cause irritation if powder aeroled and inhaled/ contact with eyes, skin, mucous membranes. Lead to toxicity
341
Q

can omeprazole gastro-resistant tablets?

reason?

A

no.
Omeprazole is not stable at acidic pH
and crushing the tablet would reduce its bioavailability.

consider alt formulation- Oral suspension,
Enteric coated pellets/granules encapsulated in capsules

342
Q

levothyroxine 50 mcg daily for the past 5 years.- likely indication?

A

Primary hypothyroidism

343
Q

Which tablet properties will impact how easy it is to split a tablet?

A

Size, mechanical strength, shape mostly!
May be issue if narrow therapeutic index drug (NTI).

try to justify- for exams

344
Q

NTI drugs- meaning and therefore need to od what?

A

only a small difference between the minimum effective concentrations and the minimum toxic concentrations in the blood.

  • Need to be careful at the start, when titrating the dose
  • Monitoring will be required
345
Q

Which tablet test do you think will be affected

by tablet splitting?

A

Think of the main tablets tests and which ones will be affected by performing the test on half of the tablet!

Friability test
Uniformity of content
Disintegration

346
Q

advice for splitting levothyroxine?

A

May be better to take one every other day, taking half tablet, not enough for therapeutic effect on liver

Long term effect: more about half life of med: check emc/ BP
7 days half life = may not have effect if just missed one dose.

Lab 2 (12 decks)

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