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S1 Pharmaceutics > Solid State > Flashcards

Solid State Flashcards

1
Q

What are solids ?

A
  • Physical state of matter.
    • Rigid structure.
    • Resistance to changes in shape and volume.
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2
Q

Importance of solids in pharmacy ?

A
  • better patient compliance and product stability of solid-state systems, when compared to liquid-based
    products.
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3
Q

What are the physical characteristics of solids ?

A
  • solubility
  • mechanical properties, which determine drug release profile.
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4
Q

What things do Solid properties influence decisions of ?

A
  • crystallisation methods, particle size reduction.
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5
Q

What are the 2 types of solid components ?

A
  • amorphous
  • crystalline
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6
Q

2 types of crystalline forms ?

A
  • single component
  • multi- component
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7
Q

Types of multi-component forms ?

A
  • co-crystals
  • hydrates
  • solvates
  • salts
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8
Q

Degrees of order experienced in pharmaceutical solids

A
  • on slide 8
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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
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10
Q

3 features of crystalline solids ?

A
  • Defined geometric shape with flat faces (habit).
    • Sharp melting point.
    • Thermodynamically stable.
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11
Q

What are crystalline solids described in terms of ?

A
  • unit cells (the smallest repeating unit of a lattice)
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12
Q

What 3 things can crystals consist of ?

A
  • atoms, molecules, or ions.
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13
Q

Difference between salts and cocrystals ?

A
  • Salts are composed of ions
  • cocrystals of neutral molecules
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14
Q

What happens if proton transfer has not occurred ?

A
  • it is a cocrystal
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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
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16
Q

How are cocrystals formed ?

A
  • by hydrogen bonds between drug and another molecule (coformer)
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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
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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
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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
Q

Why do organic compounds frequently form hydrates in presence of water ?

A
  • Small molecular size of water
  • The multidirectional hydrogen bonding capability of water
26
Q

Is they hydrate less or more soluble that anhydrous form ?

A
  • less soluble than anhydrous form
  • Need to understand humidity at which anhydrous to hydrate conversion occurs.
27
Q

What is polymorphism ?

A
  • Crystalline forms with the same chemical composition but different internal structures (packing, conformation)
28
Q

What % of pharmaceutical solids exhibit polymorphs ?

A
  • More than 80%
29
Q

What is a metastable polymorph ?

A
  • more soluble but less stable
30
Q

How are polymorphs analysed ?

A
  • x ray diffraction
  • thermal behaviour
  • thermodynamic stability
31
Q

What does x ray diffraction analyse ?

A
  • crystal structure
32
Q

What 2 things does thermal behaviour analyse ?

A
  • melting point
    • heat of fusion
33
Q

Thermodynamic stability (3)

A
  • free energy
    • solubility
    • the more soluble polymorph is the less stable
34
Q

Polymorphism of Chloramphenicol ?

A

• β-polymorph more water- soluble than α-polymorph.
• β-polymorph better absorbed orally

35
Q

Ritonavir

A
  • HIV-protease inhibitor
  • found new crystal form 1998
  • new form affected dissolution rates
36
Q

What are amorphous solids ?

A
  • solid that does not posses the long-range order (periodicity) characteristic of a crystal.
37
Q

How is solubility of amorphous solids improved ?

A
  • improved by disarranging its crystalline lattice to produce a higher energy state of amorphous form.
38
Q

5 Properties of amorphous solids ?

A
  • 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
Q

What is glass transition ?

A
  • physical change from a glassy state to a rubbery
    state upon heating
40
Q

How can glass transition temperature be determined ?

A
  • using differential scanning calorimetry (DSC).
41
Q

What does the physical instability of amorphous drugs lead to ?

A
  • leads to crystallisation during storage
  • due to high energy of the amorphous compared to crystalline
42
Q

What happens to stability as solubility decreases ?

A
  • stability increases
43
Q

Gibbs free energy equation

A

△G = △ H - T △S

44
Q

If ΔG < 0

A
  • products favoured to react
45
Q

ΔG > 0

A
  • disfavoured

S1 Pharmaceutics (11 decks)

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