L134- Specification

Question 1

what is quality assurance?

Answer 1

wide ranging concept which covers all matters which collectively or individually influence the quality of a product. It is the sum total of the organised arrangements made with the object of ensuring the medicinal products are of the quality required for their intended use.”

Question 2

what are the documents for specification?

Answer 2

raw materials spec- describes the necessary chemical and physical properties of a raw material
finished product spec- describes the necessary chemical and physical
properties of a raw material

Question 3

what must a specification be like?

Answer 3

• clear and unambiguous
• reviewed regularly
• approved by an appropriate person

Question 4

what is a specification?

Answer 4

is a statement about an attribute with which the product must comply to be approved for use. Each attribute will have a separate specification.

Question 5

what needs to happen for a batch of pharmaceutical products to pass?

Answer 5

the batch needs to pass ALL specification tests.

Question 6

what are non-pharmacopoeial specifications?

Answer 6

specification thats are specific to individual product

Question 7

what are the different types of tablet specifications?

Answer 7

1) weight uniformity -official
2) Content -unofficial
3) Content uniformity -official
4) Disintegration time- official
5) Dissolution profile -official
6) Hardness- unofficial
7) Friability -official
8) Thickness- unofficial
9) Loss of drying -unofficial/official

Question 8

what is the weight uniformity specification?

Answer 8

• it ensures that all tablets contain the same amount of drug
• ensure that the patient gets a reproducible dose of the drug

Question 9

what is the method for weight uniformity?

Answer 9

• weigh individually 20 tablets from the same batch
• calculate mean weight
• batch passes if it complies with the following specification:
  1) no more than 2 tablets deviate from the mean by <80mg is 10%, 8-250mg is 7.5%, >250mg is 5%

Question 10

what is the content spec?

Answer 10

• To ensure that the average drug content of the tablets in a batch
is as stated (within limits)
 to ensure that the patient gets a reproducible dose of drug
• Used for activities such as stability studies

Question 11

what is the method for content spec?

Answer 11

• assay 10 tablets from the same batch as a “composite”
• calculate average content
• batch passes if the result is within 90 to 110 % of stated value
  • During development, use a specification of 95 to 105 % of stated

Question 12

what is the content uniformity spec?

Answer 12

• Applies to all tablets eg uncoated, coated, effervescent, chewable
• To ensure that all individual tablets of a batch contain the stated
amount of drug (within limits)
 to ensure that the patient gets a reproducible dose of drug

Question 13

what is the method of the content uniformity spec?

Answer 13

• step one
  -assay (test) individually 10 tablets from the same batch
• calculate mean drug content
• batch passes if all tablets are within 85 and 115 % of the mean - batch fails if more than one tablet is outside these limits
• batch fails if one tablet is outside 75 to 125 % of the mean
  step two
• if one tablet from stage 1 was outside 85 to 115 % of the mean
  but within 75 to 125 % of the mean
• assay (test) individually 20 more tablets from the same batch
• calculate mean drug content of the 30 tablets
• batch passes if not more than one tablet is outside 85 to 115 %
  of the mean and none is outside 75 to 125 % of the mean

Question 14

what is the disintegration time spec?

Answer 14

• Applies to all tablets eg uncoated, coated, effervescent, chewable
• To ensure that all tablets disintegrate within a specific time
 to ensure that the biological effect is reproducible
• Test equipment and conditions specified in BP (water, 37°C)

Question 15

what is the specification for disintegration time?

Answer 15

uncoated tablets 15 minutes, coated tablets 30
minutes, effervescent tablets 5 minutes, soluble tablets 3 minutes
• Most immediate-release tablets disintegrate in 5 minutes
• Enteric-coated tablets must remain intact in 0.1 M HCl for 2
hours and disintegrate in phosphate buffer pH 6.8 within 1 hour

Question 16

what is the dissolution profile spec?

Answer 16

• To ensure that the dissolution profile of the drug from the tablet is reproducible
 to ensure that the biological effect is reproducible

Question 17

what is the method for the dissolution profile spec?

Answer 17

• Test equipment specified in BP
• Test conditions reflect the stomach conditions: 0.1 M HCl
• Immediate-release tablets
- “standard” is 80 % dissolved within 15 minutes
• Sustained-release tablets
- individual specifications

Question 18

what is the hardness spec?

Answer 18

• To ensure that the tablet can withstand handling
• To ensure that the disintegration time and dissolution profile
remain within specifications

Question 19

what is the friability spec?

Answer 19

• To ensure that the tablet can withstand handling
 to ensure that the patient receives a reproducible dose of drug
• Test equipment specified in BP

Question 20

what is the method for the friability spec?

Answer 20

• weigh 20 tablets (up to 650 mg) or 10 tablets (> 650 mg) - place tablets in a drum and rotate for 100 revolutions
• weigh tablets and calculate weight loss
  • BP specification = 1 % weight loss - this is very high!!!!!
  • In development, use 0.2 % weight loss as the limit

Question 21

what is the thickness spec?

Answer 21

• Used as an in-process test during compression

* Does not vary substantially throughout a batch of tablets

Question 22

what is the loss of drying

Answer 22

• Used as an in-process test during granulation
• Refers to the granule after drying
• Generally 1 to 2 % w/w
• Expose granule to 105°C for 15 minutes and measure weight loss

Question 23

what are the types of capsule specifications?

Answer 23

1) weight uniformity

Question 24

what is the method for weight uniformity for capsules?

Answer 24

<300mg allowed 10%, >300mg allowed 7.5% deviation

Question 25

what is content uniformity method for capsules?

Answer 25

stage 1-
- assay (test) individually 10 capsules from the same batch
- calculate mean drug content
- batch passes if not more than one individual capsule is outside
85 to 115 % of mean and none is outside 75 to 125 % of mean
- batch fails if more than three individual capsules are outside 85 to 115 % of mean or if one or more capsules are outside
75 to 125 % of mean
stage 2-
if two or three capsules from stage 1 were outside 85 to 115 % of
the mean but within 75 to 125 % of the mean
- assay (test) individually 20 more capsules from the same batch
- calculate mean drug content of the 30 capsules
- batch passes if not more than three capsules are outside 85 to
115 % of the mean and none is outside 75 to 125 % of the mean

Question 26

what is the disintegration time for capsules?

Answer 26

30minutes
- shells take about 3 to 5 minutes to disintegrate
- most fills disintegrate by 10 minutes
• Enteric-coated capsules must remain intact in 0.1 M HCl for 2 hours and disintegrate in phosphate buffer pH 6.8 within 1 hour