material sciences

define medicine

formulated drug product that contains active drug substance

define ‘solid particle’

solid drug particles contain many drug molecules

drug molecules pack together to make particles

what 2 structures can solids take

• amorphous

• crystaline

what is the difference between amorphous and crystalline solids

• amorphous means having no definite form or distinct shape - lacks structure

• crystalline means solid has rigid, repeating structure

what are the characteristics of amorphous solids

• fast dissolution

• dissolves in any temp

• stable without water

• collapses in presence of water

• has critical formation temp

what are the characteristics of crystalline solids

• slow dissolution

• in higher temps, it will dissolve faster

• stable with or without water

• has melting point

• different arrangements

define crystalline solid

where molecules are arranged in repeating pattern aligned with each other

in crystalline structure, what is the name given to the smallest arrangement of molecules that repeats

unit cell

in crystalline structures, what is a ‘habit’

habit is the shape of the crystal

• same unit cell can grow into different habits

how many habits exist

6

why is habit (shape) important for crystalline structures

because shape affects powder flow, compaction and dissolution

for a crystalline solid, this graph shows what happens to energy as temp increases - the crystal will melt at specific temp.

why are molecules with the lowest energy or volume the most stable

because:

• the molecules are in the closest packed arrangement 

• it will have the highest crystal lattice energy which means it has the strongest bonds so the most energy is required to break the bonds

• when creating these bonds, the most energy is required to form these bonds again - system loses the most energy

what makes a material polymorphic

polymorphism is when the molecules can arrange in more than one pattern

polymorphism true or false:

• different molecule, same unit cell

• strength of bonds between molecules are same

• will affect melting point, enthalpy of fusion, dissolution rate, solubility and habit

• false - same molecule, different unit cell

• false - strength of bonds between molecules are different

• true

how to determine which polymorphic form will be the most stable

form with the strongest intermolecular bonds and is the lowest energy form

true or false: each polymorph has different thermodynamic stability

true

polymorphic graph

note that Tm means melting point temp

why are metastable crystalline solids at a higher energy/volume

because this form has weaker bonds and eventually will convert to stable form

why does metastable crystalline solid have higher bioavailability compared to stable crystalline solid (use graph in previous flashcard)

if you cool structure down too quickly, then the structure will not form as strongly packed structure so it is easier to dissolve

characteristics of polymorphs

• each form has own melting point

• each form has own enthalpy of fusion

if molecules are tightly packed together, bioavailability will be [lower/higher] because it is [easier/harder] to overcome bonds and dissolve

if molecules are tightly packed together, bioavailability will be [lower/higher] because it is [easier/harder] to overcome bonds and dissolve

there is a second component in unit cells which can either be solvents or water.

• what is hydrate

• what is solvate

• if second component is water, material is hydrate

• if second component is solvent, material is solvate

how to determine what type of hydrate material is (ie. monohydrate, dihydrate, hemihydrate)

dependent on drug: water ratio

why is it harder to dissolve a hydrate and what impact does this have on bioavailability

because water forms strong hydrogen bonds to drug which can make it harder to dissolve. this results is lower bioavailability than anhydrous materials

cyrstalline materials have no water

in simple terms, what is a amorphous material 

material with molecular structure of liquid but viscosity of solid

• high viscosity liquid - acts like a solid but particles are randomly arranged

e.g. glass - molecules are randomly arranged so some light goes through and it appears transparent or translucent vs crystalline structure has regular arrangement of molecules

what happens to a material if it is allowed to cool slowly

particles have time to arrange into regular structure so forms crystalised structure 

viscosity is low when temp is high but upon cooling down, this thickens the material

what is the glass transition temp

temp at which viscosity has become so high that it wont flow and behaves like a solid

true or false: amorphous materials will not melt on heating

true

why do amorphous materials have fast dissolution rates

because there is no crystal lattice energy to overcome

true or false: amorphous materials have higher solubilities

true

what is the disadvantage of having faster dissolution rates

material is more unstable

true or false: for amorphous materials, there is no melting point

true