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Science of medicine > crystalline vs armorphous > Flashcards

crystalline vs armorphous Flashcards

1
Q

why do we not just take the drug why do we need to put it in another form

A

poor physical and chemical properties, need to control dosage for patient requirements

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2
Q

what is a crystal

A

regular, geometric, ordered

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3
Q

what is a amorphous

A

non-crystalline, un-orgnaised, not ordered, glass

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4
Q

what is it called when a crystal goes from solid to liquid

A

melting point (Tm), has lattice energy

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5
Q

what is it called when an amorphous goes from solid to liquid

A

glass transition (Tg) , has no lattice energy

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6
Q

what does it mean to be stable

A

lowest free energy state, cant spontaneously change

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7
Q

what does meta-stable mean

A

not lowest free energy state, can potentially spontaneously change, all amorphous material are meta-stable

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8
Q

why are crystals preferred in formulation

A

amorphous material has higher solubility and dissolution rate, more unstable and more likely to recrystallise, changes in medicine is bad

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9
Q

which type of material is preferred in formulations

A

crystals

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10
Q

what does lattice mean

A

array of points, identical surroundings

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11
Q

what does motif mean

A

atoms associated with lattice point

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12
Q

what is lattice energy

A

large energy input required to change state from solid to liquid (melting enthalpy)

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13
Q

what is translational symmetry

A

repeating patterns of the crystal structure

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14
Q

how does lattice energy form

A

lattice interactions over long distances

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15
Q

what is a polymorph

A

different forms of the same compound
-same composition, can have different chemical properties

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16
Q

give some examples of multicomponent solids

A

co-crytals, salts, hydrates, salts

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17
Q

difference between cocrystals and salt

A

salt- proton transfer, 2 separate ions hold lattice together, can be crystalline, amorphous, polymorphs

cocrystals- hydrogen bonding, charge separation, unionised, crystalline, polymorphs

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18
Q

what are the purposes of using multicomponent solids

A

modify drugs

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19
Q

why use salts

A

improves properties
eg. improves solubility, powder flow, chemical/physical stability

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20
Q

how to make a salt of an API/drug

A

use the counterion

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21
Q

what do acidic drugs form and what counterions can be used to make salts of it

A

-forms anions
-aluminium, calcium, diethanolamine

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22
Q

what do basic drugs form and what counterions can be used to make salts of it

A

-cations
-acetate, benzoate, chloride

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23
Q

why cant all APIs form salt from the drug

A

some dont have ionisable groups, can make cocrystals instead

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24
Q

how to distinguish between polymorphs

A

melting point

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25
Q

what are hydrates

A

crystals that contain a water molecule in the lattice

26
Q

what are solvates

A

crystals that contain a solvent

27
Q

are hydrates and solvates stable and why

A

they are unstable due to solvent loss, if solvent is lost into the drug molecule then the physical properties of the solid form will change

28
Q

example of a hydrate

A

ampicillin trihydrate (antibiotic)

29
Q

example of a solvate

A

darunavir ethanolate (AIDS treatment)

30
Q

what does colligative mean

A

physical changes that result from adding a solute to solvent, only dependent on the concentration of solute, detects concentration of impurity

31
Q

how to see presence of impurities in a substance

A

measure the melting point of a pure substance and the sample to compare, presence of impurities will lower the melting point

32
Q

how will the presence of impurities affect melting point of a substance

A

impurites will decrease the melting point

33
Q

describe the presence of impurities in solid crystals

A

crystals are closely packed, cant fit impurities, can only have impurities in sample but not inside the crystal, insoluble impurities

34
Q

describe the presence of impurities in liquid crystals

A

molecules not closely packed, impurities soluble in liquid state, mixed together

35
Q

what are the effects of impurities in melted crystals (liquid)

A

impurities are soluble, entropy of mixing, free energy is lowered, liquid stabilised, melting point lowered

36
Q

what happens as you add impurities

A

greater stabilisation, greater entropy of mixing in liquid state, greater depression of melting point, entropy of solid to liquid increases, melting point decreases

37
Q

melting point equation at equilibrium

A

Tm =∆H (solid−liquid)/
∆S (solid−liquid)

38
Q

free energy equation at equilibrium

A

∆G = ∆H (solid−liquid) −Tm ∆S (solid−liquid) = 0

39
Q

what happens to ∆H and ∆S when impurities are added

A

∆H- unaffected
∆S- increases, melting point decreases

40
Q

schroder-van laar equation

A

1/ = 1/ - Rlnx/
Tm T0 ∆H

Tm=melting point of mixture
T0=melting point of pure substance
R=ideal gas constant
x=mole fraction of solute
∆H=enthalpy of melting of the solute

41
Q

summary of melting point

A

impurities can enter liquids but not solids due to close packing, impurities increase entropy of liquids but not solids, free energy also lowered, liquid stabilised so mp decreases

42
Q

what properties can you test to determine whether a material is crystalline or amorphous

A

lattice energy- yes=crystal
translational symmetry- yes=crystal
optical
order/disorder
ability to exclude/include other molecules- crystals exclude impurities

43
Q

what techniques can be used to analyse solids

A

x ray powder diffraction (XRPD), calorimetry, optical microscopy

44
Q

how does XRPD work

A

works due to the interferences between waves coming into a sample

45
Q

how to read a XRPD graph to determine if a material is crystalline or amorphous

A

peaks= crystalline
broad halo= amorphous
-whole pattern is important
-measures spacing between atoms (x axis) and location of atoms (y axis)

46
Q

what is constructive interference

A

when two waves are in the same direction and same phase, their amplitude gets added together and a resultant wave is obtained
-resultant wave will be higher than the original

47
Q

what does in phase mean

A

peaks line up

48
Q

what is destructive interference

A

waves cancel each other out, sum of waves is zero

49
Q

how does a wave change phase

A

changes the path length

50
Q

what happens when the wavelength of light is bigger than the object

A

no interaction

51
Q

what happens when the wavelength of light is smaller than the object

A

shadow forms

52
Q

what happens when the wavelength of light is the same as the object

A

diffraction

53
Q

how to describe a XRPD graph for polymorphs

A

-graph will have more than one line
-crystalline/amorphous and state if it is the same structure or not

54
Q

what does DSC stand for

A

differential scanning calorimetry

55
Q

what does calorimetry measure

A

changes in heat input/output when heating a material, exo/endothermic stuff

56
Q

how does DSC work

A

-sample pan and reference pan
-measure the heat required to heat the pans up and any changes in heat input is related to the sample

57
Q

why is doing DSC with a reference pan good

A

allows us to exclude changes caused by fluctuations in room temperature

58
Q

describe the 2 methods to do DSC

A
  1. same energy input, measure temperature difference
  2. maintain same heating rate for both and measure energy required
59
Q

describe the DSC graph (exothermic up) for amorphous and crystals

A

amorphous- decreases
crystal- dips down, decreases then increases

60
Q

describe a more complex DSC graph (exothermic down) for a crystal

A

big peak=melt
small dip=crystallisation
melt peak points up so it is endothermic

61
Q

how to distinguish between crystal and amorphous using optical microsopy

A

crystals- birefringence if not cubic (most pharma crystals arent cubic), light shows through crossed polars
amorphous- no birefringence

62
Q

what does optical microscopy use to distinguish crystals and amorphous materials

A

polarised light

Science of medicine (7 decks)

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