physical stability Flashcards
3 different states of medicines and excipients
-crystaline solid
-liquid/solution
-gas
whats the exception to medicines being at atmospheric pressure
- metered dose inhalers
solid liquid transition
-in solid atoms oscillate in fixed positions this means increase temperature disrupts the ordered nature of the lattice
-however they a crystaline solids they have a super high melting point
exception to having a melting point
suppository bases that melt at room temperature
liquid to solid
-feezing that creates crystals of ice which interferes with the physical stability
solid to gas
iodine can sublime.
-also freeze drying freeze water and sublime it
liquid to gas
cytoxics high vapour pressure if they spill they go into a toxic gas
evaporation
change of liquid to a vapour at a temperature below the boiling point
sublimation
solid to vapour at a tempreture below the triple point in the phase diagram
vapour pressure
-solid or liquid placed into a container and exerts a pressure at equilibrium its called a vapour pressure its always at constant pressure.
only eliquilbrium in closed system
significance of vapour pressure
-vapour pressure in solids much lower than in liquids
-if lid left off bottle water has a higher vapour pressure than drugs so it will evaporate making the concentration of the medicine increased
gas adsorption
form water layer on tablets because water vapour adsorbs on to the surface of the drug and evaporates at an equilibrium, the drug can dissolve in thus layer and can hydrolyse. also impacts flow of drug particles. depends on temp and water content in atmosphere its also reversible. can also get capillary condensation in pores.
hygroscopic
solid that adsorbs water depends on SA and Senergy more polar means more water is absorbed.
solubility changes
more than saturated the drug will crystallise out. cool makes more saturated the drug could precipitate out.
crystalline drug definition
-a solid in which the constituent molecules are packed in a regularly odered, repeating pattern extending in all three spatial dimensions, they atoms are held together by non-covalent interactions. uniform form held by electrostatic interaction or hydrogen bonding.
crystaline is most common most stable and high melting point. Physically and chemically stable
amorphous drug
no long range pattern. some amorphous material in crystaline drugs on surface. Amorphous material is less stable, this is because water lowers glass transition temperature so this makes material more plastic and more mobile which increases chemical reactivity which means chemical degradation.
why amorphous less chemically stable
Amorphous material is less stable, this is because water lowers glass transition temperature so this makes material more plastic and more mobile which increases chemical reactivity which means chemical degradation.
amorphous less physically stable
-can crystallise back out with moisture
polymorphs
same molecules with different molecular packing. they have diff chemical properties like diff solubilities and diff bioavailability’s
why choose most stable polymorphs
so there is no changes to drug in storage
hydrates
are polymorphs of drugs but have water molecules as part of the crystal structural they also have diff soluabilities .
why we need packaging
protect drug in transport, storage and use
what three materials can packaging be made out of
glass- not permeable no molecules can pass through
plastics and rubber which is semi permeable so some molecules can diffuse through
semi permeability depends on
-SA
-thickness
-time
-differences in partial vapour pressure
permeation law
Ficks first law
examples of permeations
-water vapour: coming in and out
-o2
-co2
leachables
something coming out packaging into medicines.
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”.
What influences the accumulation of leachables in a medicine (solution)?
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
adsorption
Adsorption of solute (drug/excipient) to surface (packaging/container) occurs when chemical grps present that allow interaction
Factors that affect extent of adsorption:
Solute concentration
pH –extent of ionisation – unionised more likely to be adsorbed
Temperature-exothermic lower temp more adsorbed
Surface area
weak acid ionisation
Weak acids (e.g., aspirin) will tend to ionize (lose a proton) more in higher pH (more basic) conditions, whereas weak bases (e.g., morphine) will ionize more in lower pH (more acidic) conditions.
adsorption vs absorption
ad on surface
ab inside
rubber
-old and natural high leachable some new have less
-all have adsorption and permeation
plastics
-placticers and antioxidants are common leachable
-all permeation
-all adsorption
most is pic
