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UNI: FUN- D. Pharmaceutics > D12. Stability: physical processes > Flashcards

D12. Stability: physical processes Flashcards

1
Q

why is stability important?

A

Stability is an essential factor in the safety, efficacy and quality of a medicine- requires chemical and physical stability

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2
Q

what 3 different states are drugs and excipients found in?

A

crystalline solid, liquid/solution, gas

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3
Q

equilibrium between phases is dependent on?

A

temperature and pressure

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4
Q

medicines are at atmospheric pressure with the exception of what?

A

aerosols

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5
Q

Describe a metered dose inhaler

A

In head space, gases liquefied in a closed container in equilibria
with gas phase (high vapour pressure)
ONE NOTE

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6
Q

Describe solid- liquid transition

A

Atoms in solid state oscillate in fixed positions-> increase in temperature -> disrupt ordered nature of lattice

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7
Q

most drugs and excipients with high melting points are stable at what temp?

A

room temp

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8
Q

Describe liquid-solid transition

A

Freezing water in a liquid medicine creates crystals of ice that interfere with physical stability of suspensions and emulsions

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9
Q

Describe solid- gas transition

A

-Iodine can sublime directly to gas (high vapour pressure-more later)
-Freeze drying
-Drug frozen in water-> dried by a sublimation process (reduction pressure/temperature)

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10
Q

Describe liquid to gas transition

A

Cytotoxics: High vapour pressure (for example carmustine) and if spilt can volatilise to a gas (hazard when working with cytotoxics)

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11
Q

what is evaporation?

A

Change of liquid into a vapour at a temperature below the boiling point

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12
Q

What is sublimation?

A

Change of solid into a vapour at a temperature below the triple point in the phase diagram (direct transition from solid to gas)

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13
Q

what is vapour pressure?

A

Pressure exerted by the vapour at equilibrium is the vapour pressure (constant temperature). The condensed phase (liquid/solid) placed in closed container.

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14
Q

Describe evaporation

A

Evaporation takes place at the surface of a liquid, where molecules with highest kinetic energy escape

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15
Q

Describe the equilibrium in a closed container?

A

Equilibrium between evaporation & condensation in closed container at constant temperature

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16
Q

why is the vapour pressure of solids much lower than liquids?

A

due to stronger inter-molecular forces in solids. In solids, evaporation is more common than sublimation

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17
Q

how can evaporation occur with pharmaceutical liquids?

A

Pharmaceutical liquids (suspensions, emulsions, solutions)- aqueous vehiclecan evaporate if the lid left off on the bottle. The non-volatile drugs/ low vapour pressures do not escape which can increase concentration of drug in suspension/ solution

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18
Q

Describe gas adsorption

A

water vapour in the atmosphere can adsorb onto drugs and excipients and form a thin water layer. This could cause chemical degradation (hydrolysis) and also impact the flow and cohesive properties of drug particles

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19
Q

Describe physical adsorption process (no chemical bonds)

A

-Mono/multi-layers on the surface
-Adsorption-desorption reversible
-Capillary condensation into pores on the surface of the material

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20
Q

What is gas adsorption dependent on?

A

-Dependant on temperature, pressure & amount of water vapour in the atmosphere (humidity)
-Decreases with increase in temperature
-Increases with increases in water vapour at constant temp

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21
Q

what is a hygroscopic solid?

A

describes a solid that adsorbs water

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22
Q

what is a hygroscopic solid dependent on?

A

Dependant on the surface area and surface energy of the drug particle (greater the polar component more water absorbed )

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23
Q

what is equilibrium (or Thermodynamic) Solubility?

A

the concentration of drug in a saturated solution when excess solid is present, and solution and solid are at equilibrium
ONE NOTE

24
Q

what is supersaturation/nucleation?

A

solid drug ppt out

25
Q

what can happen to a drug in solution if not stored as labelled i.e at lower temperatures ?

A

Potential for ppt of drugs but concentration remains the same

26
Q

solubility of solute (drug) decreases with what change in temperature?

A

decreases in temperature

27
Q

what is a crystalline structure?

A

a solid in which the constituent molecules are packed in a regularly ordered, repeating pattern extending in all three spatial dimensions; held together by non-covalent interactions

28
Q

what is a amorphous structure?

A

Materials with no apparent crystalline form, i.e. no long range order

29
Q

surface amorphous content are induced by?

A

processing e.g milling/micronising)

30
Q

Describe the physical form of a drug?

A

-Most drugs (organic molecules) are crystalline and designed to be inherently stable by medicinal chemists
-High melting points so that they are stable at room temperature and during processing
-The most stable polymorph/hydrate is used

31
Q

Describe the stability of amorphous materials

A

Amorphous materials generally less stable (physical and chemical stability) than corresponding crystalline form.

32
Q

Describe the chemical stability of amorphous materials

A

Water lowers the glass transition temperature (Tg) -> material more plastic-> increases the molecular mobility and ↑ chemical reactivity (more prone to chemical degradation than corresponding crystalline form)

33
Q

Describe the physical stability of amorphous materials

A

amorphous phases can crystallise with exposure to moisture

34
Q

what is polymorphism?

A

When two crystals have the same chemical composition but different molecular packing they are polymorphs

35
Q

what is polymorphism?

A

When two crystals have the same chemical composition but different molecular packing they are polymorphs

36
Q

Describe polymorphs

A

-Polymorphs have different physical & chemical properties
-Melting point, density, solubility, bioavailability, processing properties
-The more stable the polymorph the lower the solubility

37
Q

What is a metastable polymorph

A

-A metastable polymorph is a form of a substance that is stable under certain conditions but is not the most energetically favorable, and may eventually transform into a more stable form.
-A metastable form can convert to more stable form in both solid and liquids (tablets and suspensions)

38
Q

Describe a meta stable polymorph

A

it has a high solubility so is therefore absorbed in the GIT. It has a high drug plasma concentration.

39
Q

Describe what can happen to a meta stable polymorph during storage?

A

-it can convert to the most stable polymorph which has a low solubility
-It will be absorbed in GIT with a lower drug plasma concentration= potential for reduced pharmacological effect. Therefore solution is to start with the most stable polymorph and no changes on storage

40
Q

what are hydrates?

A

-polymorphs with the presence of water molecules as an integral part of crystal structure
-these in turn influence: solubility, stability, dissolution rate, bioavailability

41
Q

Describe packaging

A

-protection of the medicine during transportation, storage and use
-it can be made of glass (not permeable), plastics and rubber

42
Q

why are plastics and rubbers commonly used (semi permeable barrier) as packaging?

A

-can be permeable to oxygen, water vapour, carbon dioxide
-components of the medicine can also permeate through the packaging e.g parabens/antibacterials, flavorants, water vapour and oils
-Permeation through plastic barrier depends on area, thickness of the barrier, time, differences in partial vapour pressure across the barrier
-Occurs by diffusion

43
Q

Permeation is described by what?

A

Fick’s first law (rate of diffusion)

44
Q

what is fick’s first law?

A

dm/ dt = -DA (dC/ dx)
where:
dm= mass of substance diffusing in time dt across aea A under the influence of a concentration gradient dC/ dx
-(minus sign denotes the diffusion taking place from an area of high concentration to a low concentration), D is the diffusion coefficient of the permeant
ONE NOTE

45
Q

What is total water vapour ingress?

A

total process of water moving into packaging from all separate components, for example, lid, bottle, outer protective pouch (leakage through microscopic cracks and pinholes)

46
Q

Describe water vapour loss

A

-IV solutions in flexible plastic packaging- shelf life of the medicine is limited
-Can be controlled with foil overwrap

47
Q

What are OTHER packaging problems?

A

-Problems can arise from leachables, discolouration, absorption or adsorption from the medicine (either solid or solution). These are all dependent on temperature, humidity and storage time.
-higher temperatures and humidity increase the likelihood

48
Q

Leachables definition from FDA?

A

-”Organic and inorganic chemical species that can be released from the surfaces of components used in storage of drug products (medicine) under conditions of normal use”.

49
Q

what influences the accumulation of leachables in a medicine (solution)?

A

-Initial amt of leachable in the container
-Solubility limit of the leachable in solution
-Partitioning of the leachable between the container and the solution
-Migration of the leachable from the container into solution

50
Q

Describe the packaging problem of adsorption (drug/ excipient) from solution to container surface

A

Adsorption of solute (drug/excipient) to surface (packaging/container) occurs when chemical groups present that allow interaction

51
Q

what factors affect the extent of adsorption?

A

-Solute concentration
-pH –extent of ionisation – unionised more likely to be adsorbed
-Temperature-exothermic -> lower temp more adsorbed
-Surface area

52
Q

what are the types of glass container materials?

A

-Type I (borosilicate)- chemically resistant and low leachables, primarily used for parenteral medicines
-Types II and III (soda lime)- Type II suitable for buffered solutions, Type III used only for dry medicines (tablets/powders)
ONE NOTE

53
Q

Compare the compatibility of plastic container materials

A

ONE NOTE

54
Q

Describe PVC plastic container material

A

PVC –high potential for leachables, permeation and adsorption of insulin and other proteins, vitamin A and warfarin adsorbed (drugs present as additives)

55
Q

compare the compatibility of rubber container materials

A

ONE NOTE

UNI: FUN- D. Pharmaceutics (10 decks)

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