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Pharmaceutics Year 2 > Section 1 - Drug Stability > Flashcards

Section 1 - Drug Stability Flashcards

1
Q

What is drug stability?

A

The extent to which a product retains the same properties and characteristics it possessed at the time of manufacture

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2
Q

What does drug stability refer to?

A

Shelf life

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3
Q

What are the 3 areas of concern with drug stability?

A

1) Chemical - active ingredients retain chemical integrity and potency
2) Physical - dissolution and appearance are retained
3) Microbiological - sterility or resistance to microbial growth are retained

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4
Q

What can chemical degradation of active ingredients lead to?

A
  • Inaccuracy in dosing

- Possible therapeutic failure

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5
Q

What is the allowed amount of degradation?

A

2-10%, but tighter control if the degradants are toxic

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6
Q

What can physical degradation lead to?

A
  • Reduced bioavailability

- Reduced efficacy

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7
Q

What can cause physical degradation?

A

Physicochemical changes to active or excipient ingredients

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8
Q

What are some examples of physicochemical changes that can cause physical degradation?

A
  • Production of polymorphs
  • Loss of volatiles
  • Dissolution changes from aging
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9
Q

What are some examples of physicochemical changes that don’t affect efficacy, but affect elegance?

A
  • Mottling of tablets
  • Caking of suspensions
  • Colour changes of solutions
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10
Q

How can products resist microbial growth?

A

Preservatives, which must retain efficacy over the entire shelf-life

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11
Q

What is hydrolysis?

A

Decomposition of a drug through a reaction with water

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12
Q

In a hydrolysis reaction, water acts as a _____ and attacks _____

A
  • Nucleophilic agent

- Attacks electrophilic sites of a drug molecule

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13
Q

What are the most common functional groups involved in hydrolysis reactions?

A

Carboxyl derivatives

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14
Q

Why are penicillins susceptible to hydrolysis?

A

Because of the steric strain on their 4 membered beta-lactam ring

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15
Q

Oxidation reactions are often mediated through _____

A

Atmospheric oxygen

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16
Q

What is different about the products of oxidative processes?

A

They are usually electronically more conjugated, so their colour and scent change

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17
Q

In what types of solutions can oxidation reactions occur?

A
  • Aqueous
  • Non-aqueous
  • Solid state
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18
Q

Can oxidation reactions cause products to become unfit?

A

Yes

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19
Q

What are the 3 types of oxidation reactions?

A
  • Loss of electrons
  • Loss of hydrogen
  • Gain of oxygen
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20
Q

Since oxidation is the loss of electrons, what generally goes along with the loss of electrons?

A

Change in structure and transfer of protons

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21
Q

What is an autoxidative reaction?

A

An oxidation reaction that requires a free-radical and occurs spontaneously

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22
Q

What are the 3 steps of an autoxidative reaction and what occurs in each step?

A

1) Initiation - generation of a free radical
2) Propagation - further release of free radicals
3) Termination - free radicals come together to form a non-radical

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23
Q

What is photolysis?

A

When light provides the energy for initiation of an oxidative process (although not always oxidative)

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24
Q

What may happen when electromagnetic radiation is absorbed by a molecule?

A

1) Molecule decomposes with release of free radical
2) Energy is retained, causing a chemical change
3) Energy is converted to heat and no reaction occurs
4) Absorbing molecules emit light of a different wavelength

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25
Q

What are 2 examples of dehydration reactions?

A

1) Tetracycline -> epidehydrotetracycline

2) Prostaglandin E2 -> prostaglandin A2

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26
Q

Is dehydration a chemical change?

A

No, it changes the crystal habit of the drug which may result in solubility changes

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27
Q

What can dehydration produce?

A

Pseudopolymorphs

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28
Q

What are the 5 types of chemical degradation reactions?

A

1) Hydrolysis
2) Oxidation
3) Photolysis
4) Dehydration
5) Racemization

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29
Q

Polymorphs differ in ______

A

Crystal structure and crystal energies

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30
Q

Can polymorphs cause a product to be unusable?

A

Yes, sometimes

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31
Q

What is needed for a drug to be lost through vaporization?

A

The drug needs a high vapor pressure

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32
Q

What is an example of physical degradation that occurs in tablets?

A

Hardening or softening, which alters disintegration and bioavailability

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33
Q

What are 4 types of physical degradations?

A

1) Polymorphism
2) Vaporization
3) Aging
4) Adsorption

34
Q

What occurs in adsorption?

A

Drug is lost to packaging materials

35
Q

Which drug delivery method is most prone to adsorption?

A

IV

36
Q

How can adsorption be avoided?

A

Careful selection of the container

37
Q

What is t90?

A
  • Shelf life

- The time it takes the initial concentration of the active ingredient to be decreased by 10%

38
Q

What does the order of the reaction determine?

A

The shape of the concentration-time profile

39
Q

What determines the slope of the concentration-time profile?

A

The rate constant

40
Q

Which orders of reactions are most common in drug stability?

A

Zero, first, and second

41
Q

What is a zero order reaction?

A

A constant amount of drug is eliminated per unit time; independent of concentration

42
Q

What is a first order reaction?

A

The rate of decrease of substrate molecules is proportional to the concentration of substrate molecules remaining

43
Q

What is a second order reaction?

A

The overall order of the reaction is the sum of the exponents of the concentration terms

44
Q

Is it important to make a distinction between the orders of reactions?

A

No

45
Q

Which order of kinetics are expiration dates usually based on?

A

Zero or first

46
Q

What is the unit for a first order rate constant?

A

t^-1

47
Q

What will the slope be of a plot of log[D] vs. time?

A

-k1 / 2.303

48
Q

What is constant in a first order reaction?

A

Half life

49
Q

What is the shelf life of a zero order reaction equal to?

A

0.1 [D]o / Ko

50
Q

What is plotted on the graph for a zero order reaction?

A

[D] vs. time

51
Q

What is plotted on the graph for a second order reaction?

A

1/[D] vs. time

52
Q

What are 5 factors affecting reaction rate?

A

1) Temperature
2) Catalysis
3) pH effects
4) Solvent
5) Solubility

53
Q

What are reaction rates proportional to?

A

The number of collisions between particles

54
Q

What will the slope be of a plot of log k against the inverse of absolute temperature?

A

Slope = -Ea/2.303R

55
Q

What is the typical range for Ea for drug decomposition reactions?

A

12-24 Kcal/mol

56
Q

What are 2 common catalysts of oxidation reactions?

A

Iron and copper

57
Q

How can you prevent iron and copper from catalyzing oxidation reactions?

A

Add something that kelates with them

58
Q

Reaction rates in aqueous solutions are often dependent on _____

A

The pH of the solution

59
Q

What can you learn from studying the pH effects on reaction rates?

A
  • The mechanism

- The stability of the drug

60
Q

What is plotted on a pH-rate profile?

A

Rate constant (log k for first order or k for zero order) against pH

61
Q

When would a V-shaped pH-rate profile be expected?

A

When the substrate is non-ionizable and is subject to hydrolysis

62
Q

When would a sigmoid shaped pH-rate profile be expected?

A

When the drug molecule undergoes an acid/base dissociation (an ionizable substrate)

63
Q

Do chemically-related compounds generally have similar pH-rate profiles?

A

Yes

64
Q

What are the most common solvents used to solubilize a drug?

A
  • Alcohol
  • Propylene glycol
  • Glycerol
  • Polymeric alcohols
65
Q

Do solvents have a small or large impact on stability?

A

Large

66
Q

What impact does solvent polarity have on reaction rate?

A
  • As solvent polarity increases, the rate will increase when there is a charge is developed in the activated complex
  • Rate will decrease when there is less charge in the activated complex than the starting materials
  • Rate will be unaffected when there is little or no difference in charge between reactants and activated complex
67
Q

How can solvents change pKa?

A

By shifting the dissociation equilibrium

68
Q

How can a drug be stabilized using solubility?

A

It can be made into an insoluble salt and formulated into a suspension

69
Q

What does reduced solubility in a suspension mean?

A

It decreases the amount of drug available for reaction

70
Q

What is the typical order of reaction for a drug in a solution?

A

First

71
Q

What is the typical order of reaction for a drug in suspension?

A

Zero

72
Q

What are 2 stabilization strategies?

A

1) Hydrolysis

2) Oxidation

73
Q

What is needed for hydrolysis to occur and why?

A
  • Drug must be in solution

- Exclusion of water will slow the rate

74
Q

How can hydrolysis be achieved?

A

By formulating the product as a solid dose form (tablet, capsule)

75
Q

Is total exclusion of water possible?

A

Not usually

76
Q

What can allow for control over hydrolysis rate?

A

Control of pH

77
Q

Can every drug be frozen?

A

No, only the ones that show no deleterious effect

78
Q

What can freezing do to a drug?

A
  • For some, it can increase product stability

- For others, it can increase the rate of degradation (ex: ampicillin)

79
Q

How can drugs be protected from light?

A
  • Tinted glass

- Opaque plastics

80
Q

How can oxygen be removed and what is this used for?

A
  • Oxygen is purged with inert gas (usually nitrogen) and sealed
  • Used for parenterals

Pharmaceutics Year 2 (17 decks)

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