crystalline vs armorphous Flashcards
why do we not just take the drug why do we need to put it in another form
poor physical and chemical properties, need to control dosage for patient requirements
what is a crystal
regular, geometric, ordered
what is a amorphous
non-crystalline, un-orgnaised, not ordered, glass
what is it called when a crystal goes from solid to liquid
melting point (Tm), has lattice energy
what is it called when an amorphous goes from solid to liquid
glass transition (Tg) , has no lattice energy
what does it mean to be stable
lowest free energy state, cant spontaneously change
what does meta-stable mean
not lowest free energy state, can potentially spontaneously change, all amorphous material are meta-stable
why are crystals preferred in formulation
amorphous material has higher solubility and dissolution rate, more unstable and more likely to recrystallise, changes in medicine is bad
which type of material is preferred in formulations
crystals
what does lattice mean
array of points, identical surroundings
what does motif mean
atoms associated with lattice point
what is lattice energy
large energy input required to change state from solid to liquid (melting enthalpy)
what is translational symmetry
repeating patterns of the crystal structure
how does lattice energy form
lattice interactions over long distances
what is a polymorph
different forms of the same compound
-same composition, can have different chemical properties
give some examples of multicomponent solids
co-crytals, salts, hydrates, salts
difference between cocrystals and salt
salt- proton transfer, 2 separate ions hold lattice together, can be crystalline, amorphous, polymorphs
cocrystals- hydrogen bonding, charge separation, unionised, crystalline, polymorphs
what are the purposes of using multicomponent solids
modify drugs
why use salts
improves properties
eg. improves solubility, powder flow, chemical/physical stability
how to make a salt of an API/drug
use the counterion
what do acidic drugs form and what counterions can be used to make salts of it
-forms anions
-aluminium, calcium, diethanolamine
what do basic drugs form and what counterions can be used to make salts of it
-cations
-acetate, benzoate, chloride
why cant all APIs form salt from the drug
some dont have ionisable groups, can make cocrystals instead
how to distinguish between polymorphs
melting point
what are hydrates
crystals that contain a water molecule in the lattice
what are solvates
crystals that contain a solvent
are hydrates and solvates stable and why
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
example of a hydrate
ampicillin trihydrate (antibiotic)
example of a solvate
darunavir ethanolate (AIDS treatment)
what does colligative mean
physical changes that result from adding a solute to solvent, only dependent on the concentration of solute, detects concentration of impurity
how to see presence of impurities in a substance
measure the melting point of a pure substance and the sample to compare, presence of impurities will lower the melting point
how will the presence of impurities affect melting point of a substance
impurites will decrease the melting point
describe the presence of impurities in solid crystals
crystals are closely packed, cant fit impurities, can only have impurities in sample but not inside the crystal, insoluble impurities
describe the presence of impurities in liquid crystals
molecules not closely packed, impurities soluble in liquid state, mixed together
what are the effects of impurities in melted crystals (liquid)
impurities are soluble, entropy of mixing, free energy is lowered, liquid stabilised, melting point lowered
what happens as you add impurities
greater stabilisation, greater entropy of mixing in liquid state, greater depression of melting point, entropy of solid to liquid increases, melting point decreases
melting point equation at equilibrium
Tm =∆H (solid−liquid)/
∆S (solid−liquid)
free energy equation at equilibrium
∆G = ∆H (solid−liquid) −Tm ∆S (solid−liquid) = 0
what happens to ∆H and ∆S when impurities are added
∆H- unaffected
∆S- increases, melting point decreases
schroder-van laar equation
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
summary of melting point
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
what properties can you test to determine whether a material is crystalline or amorphous
lattice energy- yes=crystal
translational symmetry- yes=crystal
optical
order/disorder
ability to exclude/include other molecules- crystals exclude impurities
what techniques can be used to analyse solids
x ray powder diffraction (XRPD), calorimetry, optical microscopy
how does XRPD work
works due to the interferences between waves coming into a sample
how to read a XRPD graph to determine if a material is crystalline or amorphous
peaks= crystalline
broad halo= amorphous
-whole pattern is important
-measures spacing between atoms (x axis) and location of atoms (y axis)
what is constructive interference
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
what does in phase mean
peaks line up
what is destructive interference
waves cancel each other out, sum of waves is zero
how does a wave change phase
changes the path length
what happens when the wavelength of light is bigger than the object
no interaction
what happens when the wavelength of light is smaller than the object
shadow forms
what happens when the wavelength of light is the same as the object
diffraction
how to describe a XRPD graph for polymorphs
-graph will have more than one line
-crystalline/amorphous and state if it is the same structure or not
what does DSC stand for
differential scanning calorimetry
what does calorimetry measure
changes in heat input/output when heating a material, exo/endothermic stuff
how does DSC work
-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
why is doing DSC with a reference pan good
allows us to exclude changes caused by fluctuations in room temperature
describe the 2 methods to do DSC
- same energy input, measure temperature difference
- maintain same heating rate for both and measure energy required
describe the DSC graph (exothermic up) for amorphous and crystals
amorphous- decreases
crystal- dips down, decreases then increases
describe a more complex DSC graph (exothermic down) for a crystal
big peak=melt
small dip=crystallisation
melt peak points up so it is endothermic
how to distinguish between crystal and amorphous using optical microsopy
crystals- birefringence if not cubic (most pharma crystals arent cubic), light shows through crossed polars
amorphous- no birefringence
what does optical microscopy use to distinguish crystals and amorphous materials
polarised light
