Polymorphic Forms

Question 1

what are the properties of crystals?

Answer 1

• atoms + mol packed in high degree of order
• crystals -> heat -> sharp transition from solid into liquid state (melting)

e.g. NaCl, ibuprofen

Question 2

what are the properties of amorphous materials?

Answer 2

• atoms + mol arranged in random order
• amorphous substance -> heat -> softening + formation of highly viscous liq

e.g. glass, spray dried lactose monohydrate

Question 3

what is a crystallographic structure?

and what causes them

Answer 3

3D lattice where unit cell = repeating unit

due to high degree of order in crystals, periodic recurrence of atoms + mol can take place in all 3 dimensions in space

Question 4

what is a unit cell?

Answer 4

building block of crystal

described by 3 dimensions

Question 5

what are the 3 dimensions describing a unit cell?

Answer 5

a, b and c = lengths of axes

alpha, beta, gamma = angles between axes

Question 6

what are the classifications of crystal systems?

Answer 6

• 7 poss unit cells (basic crystal systems)
• give possible degrees of order of atoms + mol being only at corner of unit cell
• advanced crystallography -> 14 systems (bravais-lattice)
• consider possibility of presence of centre atoms in unit cell/edges of faces of unit cell

Question 7

how may crystal habits be modified?

Answer 7

by adding impurities

e. g. presence of surfactant in sol
- change habit by adsorbing onto crystal faces during growth

Question 8

anionic surfactant results in…

Answer 8

thin long needle

Question 9

cationic surfactant results in…

Answer 9

thin flaky plates

Question 10

what can polymorphs form crystal forms with?

Answer 10

different order of molecules or atoms

Question 11

what are the properties of polymorphs?

Answer 11

• have diff thermodynamic stability
• have diff free energies
• have diff fundamental physical prop: mp, vapour pressure, solubility

THIS AFFECTS

• have effect on manufacture of dosage forms
• have effect on pharmacological activity of dosage forms
• have effect on bioavailability

Question 12

what is enantropic transition?

Answer 12

transition between all forms

Question 13

what is monotropic transition?

Answer 13

transition from one form to another

e.g. transition from metastable form into stable form

Question 14

metastable forms are …

Answer 14

higher energy polymorphs

Question 15

what will a stable polymorph have?

Answer 15

• lowest free energy
• highest mp
• lowest solubility

Question 16

in drug delivery, why is it better to have metastable forms?

Answer 16

have better solubility

give better dissolution + bioavailability

Question 17

testosterone

Answer 17

polymorphic form I: stable form mp = 155 degrees

polymorphic forms II-IV: metastable forms (MP = 148, 144, 143)

Question 18

crystal solvates

Answer 18

crystals with solvent of crystallisation

Question 19

crystal hydrates

Answer 19

water = solvent of crystallisation

Question 20

anhydrates

Answer 20

crystals with no water of crystallisation

Question 21

what is a polymorphic solvate?

Answer 21

solvent interacts with crystal structure

when crystals lose solvent, new crystal form produced

Question 22

pseudopolymorphic solvate

Answer 22

no interaction between solvent + crystal bonding

when crystal solvate loses solvent, crystal lattice not destroyed

Question 23

what is the difference between crystal hydrates and anhydrates?

Answer 23

hydrates = less soluble + thermodynamically more stable

Question 24

what are crystal defects due to?

Answer 24

• missing atom

- impurity replacing original atom