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MPharm 2 - PH2107 > PH2107 - Solutions > Flashcards

PH2107 - Solutions Flashcards

1
Q

What is a solution?

A

Homogenous distribution of individual molecules of a substance dispersed in a solvent

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2
Q

What is a solution comprised of?

A
  • solvent or solvents

- solute

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3
Q

What is a solvent?

A

that phase in which the distribution occurs

if liquid, referred to as the vehicle solid or semi solid: base

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4
Q

What is a solute?

A

The component which is dissolved as discrete molecules or ions in the solvent

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5
Q

What appearance may a disperse system have?

A

The appearance of a solution

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6
Q

What are the two components in a disperse system?

A

one component is present as small particles or droplets (disperse phase)
the other forms the continuous phase or dispersant

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7
Q

Give examples of solution preparations

A

IV injection
Infusion liquid solution molecules in a solvent (water or buffer)
Numerous OTC products (cough syrup)

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8
Q

Give examples of disperse preparations

A 
Lotion - calamine lotion
Suspension - Calpol
Mixture - kaolin and morphine
Inhaler - Evohaler
Total Parenteral Nutrition (TPN)
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9
Q

What is dissolution?

A

The process whereby a molecule at the exterior particulate interface is no longer bound (or associated) to other molecules in the particle

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10
Q

What is dissolution characterised by?

A

Dissolution is a kinetic process, characterised by a dissolution rate

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11
Q

What factors is the dissolution rate determined by?

A
  • association constant (Ka)
  • temperature
  • free energy of solvation
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12
Q

What increases the tendency to dissolve?

A

The more similar the solute and the solvent are in polarity, the greater the tendency to dissolve

LIKE DISSOLVES LIKE

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13
Q

What are batches of synthetic drug produced as?

A

Large solid structures

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14
Q

Describe a crystalline structure

A

Has a defined structure, arranged in a regular, periodic manner

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15
Q

Describe an amorphous structure

A

Lacks any defined structure

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16
Q

What does post synthesis milling reduce solid drug structures down to?

A

A finely powdered particles

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17
Q

What is a particulate?

A

Particles in the range < 1um

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18
Q

What are forces that bind two adjacent molecules together overcome by?

A

Attractive forces between molecules of solvent

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19
Q

What happens when a solute molecule is freed from its crystal or other particle?

A

It becomes solvated within a solvation shell

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20
Q

How do solvent molecules orientate themselves around a solute?

A

In a complementary manner

- solvent delta- towards delta+ of solute

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21
Q

What happens to a solvation shell when more solvent is added to a solution?

A

A less strong, outer shell is formed

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22
Q

Eventually, how will the solute and solvation shells exist?

A

In a ‘sea’ of free/bulk solvent molecules

23
Q

What is caused when the association of solvent molecules is very strong?

A

Permanently bound water

24
Q

How is permanently bound water removed?

A

Cannot be removed without breaking down molecule

25
Q

What is a dissociation constant, Kd?

A

A specific type of equilibrium constant that measures the propensity of a larger object to separate (dissociate) reversibly into smaller components, as when a complex falls apart into its component molecules, or when a salt separates into its component ions

26
Q

What is the equation for Kd in a pure crystal?

A

AA A + A

27
Q

What is the equation for Kd in a non pure crystal (e.g. salt or formulation)?

A

AxBy xA + yB

28
Q

How can dissolution be accelerated?

A

Heat input: Higher temperature increases Brownian
motion causing greater collision between solvent
molecules and molecules at crystal surface

High shear: vortex mixing increases
Interaction between solvent molecules
and crystal

Ultrasonication: ultrasonic waves pass
through crystal, transmitted through water,
physically causes them to shake apart and
interact with solvent faster

29
Q

How does heat input accelerate dissolution?

A

Higher temperatures increases Brownian motion causing greater collision between solvent molecules and molecules at crystal surface

30
Q

How does high shear accelerate dissolution?

A

Vortex mixing increases interaction between solvent molecules and crystal

31
Q

How does ultrasonification accelerate dissolution?

A

Ultrasonic waves pass through the crystal, transmitted through water, physically causes them to shake apart and interact with the solvent faster

32
Q

What is solubility?

A

The amount of a substance (mass or moles) that will dissolve in a specific volume of solvent, Csol

33
Q

How is solubility determined?

A
  1. Excess solid drug added to solvent until no more dissolves, at a specific temperature
  2. Separate excess (centrifugation)
  3. Analyse supernatant (UV or HPLC)
  4. Often, very large dilution of supernatant necessary (e.g. x 1000)
  5. Replication > x3
  6. Typical data form
    - mg/mL
    - mol/L
  7. For precision purposes, always accompanied by SD or SEM
34
Q

What does ‘high solubility’ or ‘poor solubility’ mean?

A

Not much! It depends on your frame of reference

35
Q

Which factor is solubility highly dependent?

A

Temperature
- higher temperature = higher solubility

Solubility should have associated temperature

36
Q

What is a saturated solution?

A

The point at which the solution has reached the solubility point

  • immediately prior to drug precipitation
  • at which no more drug can be solvated
37
Q

Why is solubility important?

A

The first step in preparing a formulation is to dissolve the drug in an appropriate solvent
- drugs in solid phase cannot penetrate biological membranes

38
Q

What state must a drug be in before transport and absorption?

A

The drug substance must be in solution

39
Q

The higher the concentration, the higher the . . .

A
  • dose, hence pharmacological effect

- chemical potential (tendency to migrate from high to low concentration)

40
Q

What factor affects the rate of migration?

A

The higher the difference in chemical potential, the greater the concentration gradient

41
Q

What is solvent polarity determined by?

A

Dielectric constant

42
Q

What features of a drug affect its solubility?

A

Molecular features (moieties) broadly described as polar or non-polar

43
Q

What are the features of alkyl regions?

A

Don’t ionise
Non-polar
Lipophilic

44
Q

What is the relationship between alkyl regions and lipophilicity?

A

The greater the extent of alkyl regions, the greater the lipophilicity

45
Q

What do functional groups introduce into the molecule?

A

Varying levels of polarity and LogP values

46
Q

What effect does the ionic state of ionisable functional groups have?

A

The molecule’s hydrophilicity or lipophilicity

47
Q

How do charged drugs exist?

A

They cannot exist on their own - they must exist as salts

48
Q

Which drugs need to be lipophilic to be effective?

A

Drugs for topical delivery to the skin

49
Q

What is a salt?

A

An ion and a counterion

50
Q

What effect can the counterion have?

A
  • ion pair association constant (not too strong)
  • toxicity levels of counterion in formulation
  • counterion interaction with excipients / packaging (e.g. Cl- is corrosive)
  • lability of drug to acid used to make the salt
51
Q

What is crystallisation?

A

The converse of solubilisation

- crystal purity desired

52
Q

What is a polymorphic structure?

A

When more than 1 crystal lattice forms simultaneously

53
Q

What effect does shear force in milling have?

A

Can alter crystal purity

MPharm 2 - PH2107 (26 decks)

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