L16 - drug solubility & dissolution rate 1

Question 1

drugs function as what in body?

Answer 1

solution (drugs have to be dissolved before being absorbed)

Question 2

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

Answer 2

eliminated in gi tract before dissolution

Question 3

what is bioavailability?

Answer 3

rate and extent of absorption

Question 4

what happens if there is low aqueous solubility?

Answer 4

poor BA

Question 5

define solution

Answer 5

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

Question 6

deine miscibility

Answer 6

solution can be solid, liquid or gas

Question 7

define solvent

Answer 7

compound that determines phase of solution

Question 8

solute

Answer 8

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

Question 9

saturated solutions

Answer 9

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

Question 10

define solubility (quant terms)

Answer 10

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)

Question 11

define solubility (qual way)

Answer 11

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

Question 12

unsaturated or sub saturated solution

Answer 12

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

Question 13

supersaturated solution

Answer 13

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

Question 14

what amount of solute is not consisted soluble at all?

Answer 14

1mg/ml

Question 15

ppm

Answer 15

parts per million

Question 16

ppb

Answer 16

parts per billion

Question 17

% w/w

Answer 17

number of grams of solute in 100g of total solution

Question 18

% w/v

Answer 18

number of grams of solute in 100ml of solution

Question 19

molarity

Answer 19

moles per LITRE

Question 20

molality

Answer 20

number of moles of compound associated with 1kg of solvent

Question 21

normality

Answer 21

number of protons in a compound

Question 22

mole fraction

Answer 22

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

Question 23

class I drugs

Answer 23

high permeability, high solubility

Question 24

class 2 drugs

Answer 24

low solubility, high permeability

Question 25

class 3 drugs

Answer 25

low permeability, high solubility

Question 26

class 4 drugs

Answer 26

poor permeability and poor solubility

Question 27

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

Answer 27

- solubility across intestinal pH range - permeability across GI mucosa

Question 28

dispersion systems

Answer 28

emulsions & suspensions

Question 29

colloidal dispersions

Answer 29

2 phases

Question 30

what are solutions of marcomolecular material?

Answer 30

polymer material

Question 31

micelles

Answer 31

association colloids

Question 32

microemulsions

Answer 32

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

Question 33

dissolution rate

Answer 33

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

Question 34

describe how drug passes gi barrier into blood

Answer 34

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

Question 35

explain how solute molecules are released from drug particle

Answer 35

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)

Question 36

what is rate of dissolution determined by?

Answer 36

slower step (diffusion of solute through static boundary layer)

Question 37

ficks law

Answer 37

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

Question 38

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

Answer 38

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

Question 39

what can drug dissolution be increased by?

Answer 39

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

Question 40

noyes Whitney equation describing dissolution rate of a drug

Answer 40

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

Question 41

dissolution rate constant equation

Answer 41

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

Question 42

how to increase dissolution rate, k

Answer 42

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

Question 43

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

Answer 43

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

Question 44

if drug dissolution is very slow what happens?

Answer 44

- dissolution could be rate limiting step - can affect drug bioavailability

Question 45

factors affecting dissolution rate

Answer 45

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

Question 46

what affects A, surface area of undissolved solid?

Answer 46

- size of particles - porosity - dispersibility - surfactants and bile salts

Question 47

what affects Cs, solubility in dissolution medium?

Answer 47

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

Question 48

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

Answer 48

- volume of dissolution - any process that removes solute from solvent - absorption & gi fluid available

Question 49

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

Answer 49

- viscosity of solvent (gi fluids) - presence of food

Question 50

what affects h, thickness of boundary layer?

Answer 50

- stirring - gi motility

Question 51

how does particle size increase DR?

Answer 51

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

Question 52

what types of drugs does aggregation occur in?

Answer 52

poorly soluble hydrophobic drugs

Question 53

what happens if you increase temp?

Answer 53

- 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

Question 54

how does structure of the solute affect DR?

Answer 54

- phenol more soluble than benzene in water - salt form can be used to increase solubility

Question 55

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

Answer 55

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