Solid State Flashcards
1
Q
What are solids ?
A
- Physical state of matter.
• Rigid structure.
• Resistance to changes in shape and volume.
2
Q
Importance of solids in pharmacy ?
A
- better patient compliance and product stability of solid-state systems, when compared to liquid-based
products.
3
Q
What are the physical characteristics of solids ?
A
- solubility
- mechanical properties, which determine drug release profile.
4
Q
What things do Solid properties influence decisions of ?
A
- crystallisation methods, particle size reduction.
5
Q
What are the 2 types of solid components ?
A
- amorphous
- crystalline
6
Q
2 types of crystalline forms ?
A
- single component
- multi- component
7
Q
Types of multi-component forms ?
A
- co-crystals
- hydrates
- solvates
- salts
8
Q
Degrees of order experienced in pharmaceutical solids
A
- on slide 8
9
Q
What are crystalline solids ?
A
- solid in which the atoms or molecules are arranged in a pattern that repeats periodically in 3 dimensions to an infinite extent
10
Q
3 features of crystalline solids ?
A
- Defined geometric shape with flat faces (habit).
• Sharp melting point.
• Thermodynamically stable.
11
Q
What are crystalline solids described in terms of ?
A
- unit cells (the smallest repeating unit of a lattice)
12
Q
What 3 things can crystals consist of ?
A
- atoms, molecules, or ions.
13
Q
Difference between salts and cocrystals ?
A
- Salts are composed of ions
- cocrystals of neutral molecules
14
Q
What happens if proton transfer has not occurred ?
A
- it is a cocrystal
15
Q
What happens if the proton resides on the base ?
A
- then proton transfer has occurred
- the crystalline acid−base complex is a salt
16
Q
How are cocrystals formed ?
A
- by hydrogen bonds between drug and another molecule (coformer)
17
Q
4 reasons to use cocrystals ?
A
- Improve drug physicochemical properties
(solubility, stability, mechanical properties)
• Are patentable
• Can be made for non-ionizable drugs
• Modulate drug solubility
18
Q
Technological innovation of cocrystals
A
- Design of crystals with multiple components, i.e. drug-drug cocrystals
– Develop large number of cocrystals for a given drug
19
Q
Motivation for cocrystal discovery
A
- Enhanced product performance, controlled delivery
– IP protection
20
Q
Customize material properties of cocrystals
A
– Solubility
– Dissolution
– Bioavailability
21
Q
Why use salts ?
A
- improved physicochemical properties are possible. (solubility, stability)
• Salts are often more soluble than the free acid or free base.
• Salts of acids are often: Na+, K+, Ca+2
• Salts of bases are often: HCl, phosphate, citrate
• Melting point is often higher.
22
Q
What are hydrates ?
A
- solvent is water
23
Q
What are solvates ?
A
- solvent is other solvents
24
Q
Common organic solvents in solvates
A
- Methanol, ethanol, IPA
o Acetone
o Acetonitrile
25
Why do organic compounds frequently form hydrates in presence of water ?
- Small molecular size of water
- The multidirectional hydrogen bonding capability of water
26
Is they hydrate less or more soluble that anhydrous form ?
- less soluble than anhydrous form
- Need to understand humidity at which anhydrous to hydrate conversion occurs.
27
What is polymorphism ?
- Crystalline forms with the same chemical composition but different internal structures (packing, conformation)
28
What % of pharmaceutical solids exhibit polymorphs ?
- More than 80%
29
What is a metastable polymorph ?
- more soluble but less stable
30
How are polymorphs analysed ?
- x ray diffraction
- thermal behaviour
- thermodynamic stability
31
What does x ray diffraction analyse ?
- crystal structure
32
What 2 things does thermal behaviour analyse ?
- melting point
• heat of fusion
33
Thermodynamic stability (3)
- free energy
• solubility
• the more soluble polymorph is the less stable
34
Polymorphism of Chloramphenicol ?
• β-polymorph more water- soluble than α-polymorph.
• β-polymorph better absorbed orally
35
Ritonavir
- HIV-protease inhibitor
- found new crystal form 1998
- new form affected dissolution rates
36
What are amorphous solids ?
- solid that does not posses the long-range order (periodicity) characteristic of a crystal.
37
How is solubility of amorphous solids improved ?
- improved by disarranging its crystalline lattice to produce a higher energy state of amorphous form.
38
5 Properties of amorphous solids ?
- No long range order (have short range order )
- Exhibit a “halo" in X-ray powder diffraction patterns (compared to crystalline peaks).
- Have a glass transition temperature (Tg).
- Less physically + chemically stable than crystalline materials.
- Faster dissolution than crystalline materials.
39
What is glass transition ?
- physical change from a glassy state to a rubbery
state upon heating
40
How can glass transition temperature be determined ?
- using differential scanning calorimetry (DSC).
41
What does the physical instability of amorphous drugs lead to ?
- leads to crystallisation during storage
- due to high energy of the amorphous compared to crystalline
42
What happens to stability as solubility decreases ?
- stability increases
43
Gibbs free energy equation
△G = △ H - T △S
44
If ΔG < 0
- products favoured to react
45
ΔG > 0
- disfavoured
