Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

PHARM 125 - Pharmaceutics > Stability > Flashcards

Stability Flashcards

1
Q

Define stability

A

the extent to which a dosage form retains within specific limits, and throughout its period of storage and use, the same properties and characteristics that is possessed at the time of its manufacture

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are some factors affecting drug stability?

A

Environmental factors:

  • temperature
  • light
  • humidity
  • oxygen
  • carbon dioxide

Dosage form factors:

  • particle size
  • pH
  • solvent system composition
  • compatibility of anions and cations
  • primary container
  • additives
  • molecular binding
  • diffusion of drugs and excipients
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the four reasons you should be concerned about drug stability?

A
  1. Ensure that the patient receives the intended drug and dose
  2. Prevent appearance of contaminants or toxic compounds
  3. Exclude any decrease in bioavailability as a result of chemical or physical changes in the product
  4. Eliminate possibility of poor compliance as a result of appearance change to the product
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Define shelf-life

A

The period of time which, if stored correctly, the product is expected to retain acceptable chemical, physical, and microbiological stability

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Define expiry/expiration date

A

The date given on the product packaging which represents the end of the shelf life (expressed as month/year on packaging)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the condition for expiration?

A

On the day of expiry the drug must still retain 90% of its labeled potency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How many expiry dates are given for dry products meant to be reconsituted?

A

2 → expiration date assigned to both the reconstituted and dry product

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the different types of stability?

A

Physical → viscosity, appearance, odour, colour, suspend-ability

Chemical → pH, drug content

Microbiological → sterility, microbial load, preservative effectiveness

Therapeutic → activity, potency

Toxicological → identification of degradation products

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are signs of physical instability for solutions, suspensions, emulsions/creams, ointments, transdermal patches, and nasal aerosols?

A

Solutions → precipitation of drug or degradation products

Suspensions → caking of sediment, particle reduction

Emulsions/creams → creaming, cracking, reduction in viscosity

ointments → separation of liquid onto surface

Patches → change in drug release rate, change in adhesive characteristics

Nasal aerosols → change in particle size distribution

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is primary evidence of instability in capsules?

A

Hardening or softening

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are some things that would show evidence of instability of tablets?

A

Powdering, chipping, mottling, discolouration, and fusion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are some evidences of instability for powders and granules?

A
  • caking
  • colour change
  • swelling dur to premature effervescent reaction
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are some evidences of instabilities for lozenges and troches?

A
  • clumping
  • tackiness
  • discolouration
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the signs of instability for liquid dosage forms in general and more specifically emulsions and suspensions?

A

Generally → clarity, precipitation, mold/bacteria growth, odour, and loss of volume

Emulsions → odour, colour change, creaming, coalescence, phase separation and mold/bacteria growth

Suspensions → non-uniformity, settling, caking, crystal growth, mold/bacteria growth, odour, loss of volume

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are some of the ways you can enhance stability of emulsions?

A
  • decrease droplet size (ideally <5um)
  • Obtain optimal ratio of oil to water (40-60% product volume)
  • increase viscosity of external phase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Which is more susceptible to chemical degradation; solution or suspension?

A

Solution

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are the pharmacist’s responsibilities according to USP 1191?

A
  • dispense oldest stock first
  • store products under recommended conditions
  • watch products for evidence of instability
  • properly treat and label products that are repackaged, diluted or mixed with other products
  • dispense products in proper container closure system
  • inform and educate patients concerning proper storage and use of products → how to dispose of expired prescriptions
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is the aim of microbiological stability?

A

Prevent the presence and growth of pathogenic microorganisms which can spoil product

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is meant by CFU?

A

Colony-forming unit

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are sources of microbial contamination?

A
  • raw materials, including water
  • manufacturing environment
  • manufacturing personnel
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are the two means of preventing microbial contamination?

A
  1. Sterilization
  2. Adding preservatives
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What are the general considerations regarding preservative selection? (4)

A
  • should be effective against broad spectrum (Gram positive and negative)
  • must be soluble at needed concentration
  • must not affect safety or efficacy of the product
  • must be stable and compatible with other excipient and packing materials
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is usually the most critical parameter for determining shelf life?

A

Chemical stability → drug content of 90% of theoretical value is the MAXIMUM allowable reduction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is an overage and when is it possible?

A

Overage = combating the 10% reduction of theoretical value by adding more drug than required

Only possible where degradation products are non-toxic and dose is not critical

25
Q

What are the types of degradation reactions? (6)

A
  • hydrolysis
  • oxidation
  • isomerization
  • polymerization
  • photo-degradation
  • chemical incompatibilities
26
Q

What are the chemical groups susceptible to hydrolysis? (4)

A
  • esters (aspirin, benzocaine, procaine, atropine, scopolamine)
  • amides (lidocaine, acetaminophen)
  • lactams (penicillin, cephalosporin)
  • lactones (simvastatin)
27
Q

What are the factors effecting hydrolysis?

A
  • pH
  • buffer salts
  • ionic strength
  • presence of co-solvents
  • complexing agents
  • surfactants
28
Q

What is often included in oxidation and what can prevent it?

A

Oxidation often includes a chain reaction of free radicals

Antioxidants can prevent initiation OR propagation (by forcing termination)

29
Q

What are the important isomerization processes?

A

Racemization

Epimerization

30
Q

How can you help stabilize solvents?

A
  • replacing aqueous solvent with non-aqueous
  • solid dosage forms are usually more stable than liquids (dry powder for reconstitution, suspensions)
31
Q

How can you protect dosage forms from oxygen?

A
  • reduce the size of containers, use single use containers
  • add antioxidants (ascorbic acid, BHA, vitamin E)
  • Add chelating agents (EDTA or citric acid)
  • Sealing container with inert gas
32
Q

Give 3 examples of chemical incompatibilities

A
  1. Transesterfication of methylparaben and sorbitol to form a mixture of esters
  2. Transesterfication of aspirin with phenylephrine HCl, acetaminophen or with polyethylene glycol
  3. Lactose and amine drugs can form a glycosyl amine to form a 1-amino-2-keto sugar (Maillard reaction)
33
Q

Define reaction rate and give the formula

A

The velocity with which a reactant or reactants undergo chemical change → describes the change in concentration of a drug as a function of time

rate = +/- d[A]/dt

34
Q

What is the rate of degradation?

A

Describes a decrease in concentration, rate expression has a negative sign

35
Q

How can you figure out what the order of reaction is?

A

order is given by the sum of the powers of the concentration term(s) in the rate expression

36
Q

What is the relationship between decomposition and concentration in a zero order reaction?

A

Decomposition or loss of the drug is independent of the concentration of any reactants

d[A]/dt = -k0

37
Q

What are the units used in a zero order?

A

Units of mass or concentration/time

38
Q

What is the difference between the equations for half-life and shelf-life for zero order reactions?

A

Half-life → t0.5 = 0.5[A0]/k0

Shelf-life → t90% = 0.1[A0]/k0

39
Q

A drug suspension (125mg/mL) decays according to zero order kinetics with a reaction rate constant of 0.5mg/mL/h.

What is the concentration remaining after 3 days?

What is the half life?

A

3 days → 89 mg/mL

Half-life → 125 hours

40
Q

What is the relationship between concentration and decomposition in a first order reaction?

Which units are used?

A

Decomposition or loss of drug is directly proportional to the concentration of the reacting substance

units: 1/time or inverted time

41
Q

What is the between the reactions for half-life and shelf-life in first order reactions?

A

Half life → t0.5 = -ln0.5/k1 = 0.693/k1

Shelf-life → t0.9 = -ln0.9/k1 = 0.105/k1

42
Q

An ophthalmic solution of a drug, present at 5 mg/mL exhibits first order degradation with a rate constant of 0.0005/day.

How much drug remains after 120 days?

What is the half life?

A

after 120 days → 4.71 mg/mL

Half-life → 1386 days

43
Q

What is a pseudo-zero order reaction and how is this acheived?

A

Suspensions often display kinetics that appear to be zero order but are actually first order

Solid suspended in drug has zero order

When the drug starts to dissolve, the solution degrades by first order

44
Q

What happens when drug concentration exceeds solubility?

A

you have a zero order reaction

45
Q

An aqueous solution of drug X contains 200mg of drug per 5mL. The solubility of drug at 25 degrees is 1g/350mL in water and the first order rate constant for degradation at that temperature is 3.9 x 10-6 sec-1.

What is the zero order rate constant?

What is the shelf-life of the suspension?

A

Rate constant → 1.11 x 10^(-8) g/mL sec-1

Shelf-life → 4.2 days

46
Q

What is the Arrhenius equation and what is it used for?

A

Allows for the calculation or rate constants at various temperatures based on the activation energy for the reaction

k = Ae-Ea/RT

47
Q

A new cancer drug exhibits 1st order degradation kinetics with a rate constant of 0.0001/hr at 60 degrees and 0.0009 at 80 degrees.

What is it’s activation energy?

A

25.6 Kcal/mol

48
Q

What is the Q10 shelf-life estimation and what can it be used for?

A

Based upon activation energy rather than reaction order

Q10 = (kT + 10)/ kT

49
Q

What are the Q10 values and their activation energy corresponding to possible, likely and conservative?

A

Possible → Q10 = 2, Ea = 12.2

Likely → Q10 = 3, Ea = 19.4

Conservative → Q10 = 4, Ea = 24.5

50
Q

How do we estimate shelf-life decreases at different temperatures?

A

t90 (T2) = (t90 x T1)/ Q10(delta T)/10

51
Q

An antibiotic has a shelf life of 48 hours at 5 degrees.

What is the estimated shelf life at room temperature of 25 degrees? (set Q10 = 3)

A

5.33 hours

52
Q

What is the purpose of stability testing?

A

Provide evidence on how the quality of a drug substance/product varies with time under the influence of a variety of environmental factors like temperature, light and humidity

AND to establish a retest period for the drug substance or shelf-life and recommended storage conditions

53
Q

What is the statement from the International Conference on Harmonization on stability testing?

A

Establishes the sent of criterial including methods of assessment that a drug substance/product must conform to in order to be acceptable for use

54
Q

What is involved in stability testing during product development phase?

A

Formulator designs the stability studies to predict or establish the shelf-life and storage conditions for future batches

55
Q

What is involved in step 1 of stability testing?

A

Step 1: stability of drug SUBSTANCE

  • analytical and/or biological method development for accessing stability
    • determination or degradation products
    • mechanism of drug breakdown and conditions under which it breaks down
56
Q

What is involved in step 2 of stability testing?

A

Step 2: Stability of drug PRODUCT

  • design long-term stability studies based on drug substance stability data
  • storage of product at normal and accelerated conditions
  • preparation of lab scale batches
  • storage in proposed packaging
  • compatibility studies with excipients
  • elimination of excipients that could induce degradation
57
Q

What is involved in step 3 of stability testing?

A

Step 3: Stability of LARGE SCALE batches

  • development of stability protocol
  • large scale batch is representative of 1/10th of a commercial scale batch
  • batches are prepared in a similar fashion using similar excipients, methods and equipment
  • tested using well established analytical or biological methods to pre-determine specifications
  • detailed statistical analysis performed on each batch to determine shelf life and degree of variability between batches
58
Q

What is involved in step 4 of stability testing?

A

Step 4: Stability of COMMERCIAL batches

  • AIM: determine that each unit dose/package from every batch should remain within specification limits during shelf-life
  • stability program is designed and implemented based on information obtained during stability testing
  • frequency of testing of commercial scale batches over their shelf-life is usually less than for large scale batches used to determine shelf-life
59
Q

What are the considerations when assigning a beyond-use date?

A
  • nature of the drug and it’s degradation mechanism
  • dosage form and it’s components
  • potential for microbial proliferation
  • container it’s packaged in
  • expected storage conditions
  • intended duration of therapy

PHARM 125 - Pharmaceutics (5 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions