Tablet Testing

Question 1

What are properties of an ideal tablet?

Answer 1

• should be acceptable to patient
• contain right drug content
• pleasing appearance
• consistent weight, size and shape
• release drug in reproducible and predictable manner
• good chemical, physical and microbiological stability
• suitable packaging
• strong enough to keep shape during manufacture, processing, packaging, shipping and use
• exempt of contaminants

Question 2

What tests are performed on tablets?

Answer 2

• appearance; devoid of cracks, chipped edges and that colour is uniform
• thickness and diameter; should not exceed 5% of mean thickness
  
  • diameter can vary by 3% for tablets with diameter above 12.5mm and 5% for tablets with diameters less than 12.5mm
• uniformity of weight
• uniformity of content
• hardness and friability
• disintegration
• dissolution

Question 3

How is uniformity of dosage form measured?

Answer 3

• uniformity of mass
  
  • uncoated, film-coated tablets if API content is over 25mg or contributes to over 25 wt%
• uniformity of content
  
  • all others

Question 4

What can excessive variation in mass be a result of?

Answer 4

• formulation
• process development
• equipment maintenance

Question 5

Paracetamol tablets have been made in the following proportion:

• Paracetamol: 21
• Lactose: 37
• HPMC: 8
• Starch: 5

The weight of granules after drying was 80g. Moisture content of the dried granules was 8%.

5% w/w starch and 0.5% w/w magnesium stearate was added.

Calculate the fill weight (mg) to produce tablets containing 500mg paracetamol.

Answer 5

1. work out % API

21/71*100 = 29.6% of dry powder mix is paracetamol

2. work out w/w addition calculations

4g starch and 0.4g MgSt

84. 4g material
85. using moisture content, work out how much of granule mass is powder
86. 6g of powder
87. work out how much of this is API
88. 6 x 21/71 = 21.77g
89. do amount of API/total tablet mix as a ratio to work out fill weight
90. 77g drug/84.4g tablet mix = 0.5g drug/answer

answer = 1938mg

Question 6

What is wrong with a tablet that is too hard or soft?

Answer 6

too hard = may not disintegrate

too soft = will not sustain further processing, such as coating or shipping

Question 7

What does friability measure and what is the requirement?

Answer 7

• attrition method measures tendency to chip or fragment
• mass loss should not exceed 1%

Question 8

How do disintegrants work?

Answer 8

• enabling water entry (wicking)
• swelling
• releasing gaseous material
  
  • effervescent tablets

Question 9

Describe wicking in comparison to swelling.

Answer 9

wicking

• water uptake depends on
  
  • wettability (surfactants help)
  • pore size distribution
  • disintegrant addition
  • compression forces

swelling

• impact of porosity
• fluid absorbed, disintegrant size increased

Question 10

What is intergranular and extragranular disintegrant addition?

Answer 10

intergranular - before granulation

extra - after granulation ; 20-50% wt/wt of disintegrant added

Question 11

Why would there be a slow rate of drug dissolution?

Answer 11

no disintegrant used or conc too low

Question 12

What are properties of disintegrants?

Answer 12

• small particle size for high SA
• hygroscopic material as water absorption is important
• gas liberating for effervescent tablets

Question 13

Give exmaples of convential disintegrants and superdisintegrants

Answer 13

conventional

• starch 5-10%
  
  • poorly compressible
  • higher amount needed
  • wicking low
• microcrystalline cellulose 5-10%
  
  • wicking activity

superdisintegrants

• sodium starch glycolate 2-8%
  
  • free flowing
  • rapid swelling
• croscarmelose 1-5%
  
  • rapid swelling
  • wicking
• crospovidone 1-5%
  
  • wicking activity high

Question 14

What is dissolution testing?

Answer 14

determination of drug release rate

Question 15

What is preformance of tablets disintegration test affected by?

Answer 15

• disintegration media used
• temp during the test
• formulation factors

Question 16

What factors must be standardised in a dissolution test?

Answer 16

• factors affecting drug solubility
  
  • composition, pH and temp of dissolution medium
  • agitation speed
• factors affecting dissolution
  
  • conc of dissolved substances - sink vs non sink conditions
  • fluid flow in dissolution chamber
• factors affecting quantification
  
  • analytical method choice - sensitive enough to detect drug

Question 17

What factors affect disintegration/dissolution?

Answer 17

• solubility/hygroscopicity of powder formulation
• type and quantity of disintegrant used
• type and quantity of binder used
• addition of lubricant
• manufacture process selected
  
  • how compact were granules
  • addition of lubricants and antiadherents
  • what compression force was used - if it was too low the pores are too big for water to be trigerring disintegration

Question 18

Why is dissolution important and how can you improve it?

Answer 18

rate limiting step as drug needs to be in solution to be absorbed

• using a polymorph, salt or amorphous form
• particle size reduction
• matrix formed
  
  • drug dissolved or finely suspended in matrix
• dissolution enhancer