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SL12102 - the science of medicines > L16 - drug solubility & dissolution rate 1 > Flashcards

L16 - drug solubility & dissolution rate 1 Flashcards

1
Q

drugs function as what in body?

A

solution (drugs have to be dissolved before being absorbed)

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2
Q

what tends to happen to poorly soluble drugs in the GI tract?

A

eliminated in gi tract before dissolution

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3
Q

what is bioavailability?

A

rate and extent of absorption

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4
Q

what happens if there is low aqueous solubility?

A

poor BA

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5
Q

define solution

A

molecular dispersion formed by 2+ components which form a “one phase” homogenous system. solute + solvent = solution

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6
Q

deine miscibility

A

solution can be solid, liquid or gas

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7
Q

define solvent

A

compound that determines phase of solution

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8
Q

solute

A

other components of solution dispersed as molecules/ions throughout solvent, dissolved in the solvent

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9
Q

saturated solutions

A

solvent is in equilibrium with solid phase (solute), no more solute will dissolve in it

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10
Q

define solubility (quant terms)

A

concentration of solute in a saturated solution at a certain temp (max mass of solute that will dissolve in given ass of solvent at a certain temp)

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11
Q

define solubility (qual way)

A

spontaneous interaction of 2+ substances to form a homogenous molecular dispersion

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12
Q

unsaturated or sub saturated solution

A

conc of dissolved solute is below necessary conc for complete saturation at definite temp

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13
Q

supersaturated solution

A

contains more of the dissolved solute that it would normally contain at a definite temp (dissolution in large amounts at higher temp)

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14
Q

what amount of solute is not consisted soluble at all?

A

1mg/ml

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15
Q

ppm

A

parts per million

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16
Q

ppb

A

parts per billion

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17
Q

% w/w

A

number of grams of solute in 100g of total solution

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18
Q

% w/v

A

number of grams of solute in 100ml of solution

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19
Q

molarity

A

moles per LITRE

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20
Q

molality

A

number of moles of compound associated with 1kg of solvent

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21
Q

normality

A

number of protons in a compound

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22
Q

mole fraction

A

the known moles of the known compound over the total moles of the system

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23
Q

class I drugs

A

high permeability, high solubility

24
Q

class 2 drugs

A

low solubility, high permeability

25
Q

class 3 drugs

A

low permeability, high solubility

26
Q

class 4 drugs

A

poor permeability and poor solubility

27
Q

what does the BCS use to decide what category to classify drugs into?

A
  • solubility across intestinal pH range
  • permeability across GI mucosa
28
Q

dispersion systems

A

emulsions & suspensions

29
Q

colloidal dispersions

A

2 phases

30
Q

what are solutions of marcomolecular material?

A

polymer material

31
Q

micelles

A

association colloids

32
Q

microemulsions

A

1 phase, isotropic, both homogenous + heterogeneous, 1nm to 1um

33
Q

dissolution rate

A

how much drug particles are dissolved overtime in gi tract and how much is permeable to pass gi barrier to absorbed into blood

34
Q

describe how drug passes gi barrier into blood

A
  1. diffusion layer forms during drug dissolution, drug molecules in surface layer dissolve to form a saturated solution around particles
  2. so conc of drug particles is higher at start
  3. then after a while these particles diffuse as they are now liquid to the bulk of gi volume content
  4. dissolved drug molecules pass throughout dissolving fluid to contact absorbing mucosa + are absorbed
  5. replenished of diffusing layer by further drug dissolution so absorption continues
35
Q

explain how solute molecules are released from drug particle

A
  1. release of solute molecules from solid phase
  2. so molecules of solid solute become molecules of solid in solvent
  3. solution in contact with the solid becomes saturated Cs
  4. solute molecules migrate through diffusion layer
  5. solute molecules migrate through diffusion layer (from solid-liquid interface to bulk of solution, C)
36
Q

what is rate of dissolution determined by?

A

slower step (diffusion of solute through static boundary layer)

37
Q

ficks law

A

J = DKA changeinC / h

D= diffusion coefficient
A = diffusional SA
changeinC= Cs - C
h = thickness of boundary layer
K = partition coefficient

38
Q

rate of mass transfer of solute molecules/ions through diffusion layer is?

A
  1. directly proportional to the area available for migration and the change in C across the boundary layer
  2. inversely proportional to the thickness of the diffusion layer
39
Q

what can drug dissolution be increased by?

A
  1. increases SA of drug by decreasing particle size
  2. increased drug solubility in diffusing layer
  3. increased dissolution rate constant, k
40
Q

noyes Whitney equation describing dissolution rate of a drug

A

dm/dt = k A (Cs - C)
dm/dt= DR
k = dissolution rate constant
A = SA of dissolving drug
Cs = conc of drug in saturated diffusing layer
C = conc of drug in dissolution medium

41
Q

dissolution rate constant equation

A

k = D/Vh
D= diffusion coefficient of solute in the dissolution medium/solvent
V = volume of the dissolution medium
h = thickness of boundary layer

42
Q

how to increase dissolution rate, k

A

increase K (partition coefficient), this incorporates drug diffusion coefficient 7 diffusion layer thickness

43
Q

if dissolution is very fast or if the drug delivered remains in solution what happens to ROA?

A

ROA dependent upon its ability to travel across the absorbing membrane/ gi barrier

44
Q

if drug dissolution is very slow what happens?

A
  • dissolution could be rate limiting step
  • can affect drug bioavailability
45
Q

factors affecting dissolution rate

A
  1. A, surface area of undissolved solid
  2. Cs, solubility in dissolution medium
  3. C, conc in bulk of solutions t given time
  4. D, diffusion coefficient of solute in solvent
    4, h, thickness of boundary layer
46
Q

what affects A, surface area of undissolved solid?

A
  • size of particles
  • porosity
  • dispersibility
  • surfactants and bile salts
47
Q

what affects Cs, solubility in dissolution medium?

A
  • nature of solvent + solute
  • pH
  • co-solvents
  • crystalline form
  • presence of other compounds
  • solubility agents
  • micelles (bile salts)
48
Q

what affects C, conc in bulk of solutions t given time?

A
  • volume of dissolution
  • any process that removes solute from solvent
  • absorption & gi fluid available
49
Q

what affect does D, diffusion coefficient of solute in solvent?

A
  • viscosity of solvent (gi fluids)
  • presence of food
50
Q

what affects h, thickness of boundary layer?

A
  • stirring
  • gi motility
51
Q

how does particle size increase DR?

A

increases exposure of increasing amounts of solute to the solvent, increases BA

52
Q

what types of drugs does aggregation occur in?

A

poorly soluble hydrophobic drugs

53
Q

what happens if you increase temp?

A
  • solubility increases, but some - salts have endothermic dissociation in water
  • so up until a certain point dissolution will increase but then it will decrease again
54
Q

how does structure of the solute affect DR?

A
  • phenol more soluble than benzene in water
  • salt form can be used to increase solubility
55
Q

describe the idea of using salt form of drug instead of free weak acid

A
  • sodium salt has higher degree of dissociation in water
  • increased interaction with solvent
  • increased solubility

SL12102 - the science of medicines (26 decks)

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