Stability of excipients

Question 1

What is the importance of stability in extemporaneous preparation (3)

Answer 1

1. The stability of a medicine will determine it’s shelf life
2. The pharmacist must assign a shelf life to every product manufactured
3. For some products the BP/BPC specifies the shelf life

Question 2

what is the official BP/BPC formula for stability (3)

Answer 2

1. No comment - as stock stable for 12 months, decreases for 3 months once opened - after issued to patient stable for 4 weeks
2. Recently prepared - as stock stable for 2 weeks - after issued to patient stable for 2 weeks
3. Freshly prepared - prepared no more than 24 hrs before issue - after issued to patient stable for 2 weeks

Question 3

How is shelf life assigned for unofficial (not in BP/BPC) products (4)

Answer 3

1. For most unofficial (not in BP/BPC) products there will be no such information
2. It is usual to give unofficial products a shelf life of 2 weeks and not to prepare them more then 24 hours before supply
3. An understanding of this and the previous table is usually sufficient
4. In practice pharmacists must fully research the formula before assigning the shelf life

Question 4

What information & clues are there to the degradation pathways of a drug (5)

Answer 4

1. Reference texts such as Martindale/BP/BPC give information and clues as to the degradation pathways of the drug
2. Store in airtight containers-oxidation
3. Protect form moisture-hydrolysis
4. Protect from light-oxidation/hydrolysis
5. The manufacturers can be contacted for information about stability

Question 5

What affects the stability of a product (5)

Answer 5

1. Oxidation
2. Hydrolysis
3. Microbial growth
4. Formulation
5. Storage

Question 6

How can oxidation be reduced (5)

Answer 6

1. Storage in airtight containers
2. Adding antioxidants- which are oxidised in preference to the drug e.g. ascorbic acid
3. Boiling the water to remove any dissolved oxygen
4. Using a sequestering agent to remove any metal ions which catalyse oxidation reactions e.g. citric acid
5. Using purified water- no metal ions present

Question 7

How can hydrolysis be reduced (2)

Answer 7

1. If for internal use- formulate the product as a powder or capsule, or reduce the shelf life
2. If for external use- formulate the product with an ointment, oily or IMS base

Question 8

How can microbial growth be reduced (8)

Answer 8

1. Preservatives
2. Chloroform- active concentration 0.25%
3. Chloroform BP (100%)
4. Concentrated Chloroform Water (10%)
5. Chloroform Spirit (5%)
6. Chloroform Water Double Strength (0.5%)
7. Chloroform Water BP (0.25%)
8. Main disadvantage- Volatile

Question 9

What are p-hydroxybenzoates (4)

Answer 9

1. p-hydroxybenzoates widely used in cosmetics and pharmaceuticals-both internal and external
2. Methyl Parahydroxybenzoate is most water soluble-used to preserve aqueous phase
3. Butyl Parahydroxybenzoate is more oil soluble
4. If the patient does not wish to have a preservative included in the medicine- give the medicine a 7-day shelf life

Question 10

How does formulation affect shelf-life (3)

Answer 10

1. Very important-can either increase or decrease shelf life
2. Antioxidants/preservatives increase shelf life (see above)
3. If excipients are incompatible with drug -decrease shelf life

Question 11

what is the importance of potassium permanganate (2)

Answer 11

1. Potassium permanganate is a strong oxidising agent-will burn in contact with glycerol
2. Recommend using water as a base

Question 12

What are the incompatibilities with shelf life (2)

Answer 12

1. redox reactions
2. Acid-base reactions

Question 13

What are the factors of euganol extemporaneous preparations (6)

Answer 13

1. BP - store in airtight Containers
2. Martindale- Susceptible to oxidation in aqueous solutions
3. Oxidation increases with increase in pH
4. Studies show it is stable for 5-30 days
5. Studies show increase in shelf life at 5C
6. 2% Solution has a pH of 2-2.6

Question 14

What are the factors of aspirin extemporaneous preparations (3)

Answer 14

1. “Aspirin is stable in dry air but gradually hydrolyses in contact with moisture to acetic and salicylic acids”
2. Suggest, Best option-offer powders
3. Solution with a shelf life of 7 days or less and labelled store in a fridge

Question 15

What are the factors of simvastatin extemporaneous preparations (7)

Answer 15

1. Store in airtight containers, under nitrogen, permits the addition of an antioxidant to the drug
2. Compendium of Data Sheets - The tablets contain citric and ascorbic acids
3. Manufacturer - Stable for three days at pH 7
4. Very susceptible to oxidation
5. Tablets contain citric/ascorbic acid-cannot crush and add to water
6. ↓pH and therefore ↓ shelf life
7. Only option is to crush tablets before use or offer powders with a 7 day shelf life