Solutions

Question 1

What is dissolution? dissolution rate?

Answer 1

in any process, solids dissolve in a solvent to form solutions. 
The rate (or time to form a solution) is the dissolution rate)

Question 2

Why do we study dissolution?

Answer 2

• To show the release of a drug from the tablet is close to 100%
• To show the rate of drug release from is uniform batch to batch
• To show that the release is equivalent to those batches proven to be bioavailable and clinical effective

Question 3

what is the process of dissolution?

Answer 3

1. drug molecules are liberated from surface of particle
2. Drug is concentrated in solution at the surface (in contact with solid)
3. Solute migrates through the boundary layer to the bulk liquid by diffusion or convection
4. Local concentration of a drug decreases as it migrates from the boundary layer

Question 4

How do we increase the rate of dissolution?

Answer 4

• Increase surface area by crushing - decreases diffusion
• Increase volume of solvent to increase the concentration gradient
• stir to increase d and decrease h
• heat to increase d

Question 5

what are the factors that affect dissolution described using? what is this?

Answer 5

Notes Whitney equation

dm/dt = D.A. (Cs - C) / h

Question 6

what is the diffusion coefficient d?

Answer 6

it is used to describe solute molecule movement. for example, from surface to bulk solvent by diffusion

Question 7

How do molecules move?

Answer 7

By passive diffusion

1. By random molecular motions - go from high order to low order
2. From regions of high chemical potential (concentration) to a lower one i.e molecules move under a concentration gradient
3. 2nd law of thermodynamics - entropy increases wihh time so higher concentration (more order) moves to disorder with a lower concentration

Question 8

what is the concept of random walk?

Answer 8

Idea that molecules do not cross membranes in straight lines. They take tortuous paths. = molecules move under the influence of Brownian motion. However, overall motion (flux) is in the direction of the concentration gradient.

Question 9

what is the concept of drug absorption and solubility?

Answer 9

The cell membrane is lipophilic in nature (oil like) - the drug must be soluble in water before crossing the membrane and should also cross the membrane.

Question 10

what is the pH partitioning hypothesis?

Answer 10

pH - only the unionised form of a molecule crosses the membranes due to higher lipid solubility,
partitioning - molecules cross membranes at a rate dependant on their lipid solubility i.e LogP

Question 11

what is the henderson hasselbach equation for acids?

Answer 11

pKa = pH + log unionised/ionised

Question 12

what is the henderson hasselback equation for bases?

Answer 12

pKa = pH + log ionised/unionised

Question 13

what is the pKA?

Answer 13

The pH at which 50% of the drug is ionised and 50% is unionised.

Question 14

what is an acid and how do we distinguish ionised/unionised?

Answer 14

Proton donor.

• if pH is 2 units below pKA = it is totally unionised
• if pH is 2 units above pKa = it is totally ionised

Question 15

what is a base and how do we distinguish ionised/unionised?

Answer 15

proton acceptor.

• If pH is 2 units above pKA = totally unionised
• if pH Is 2 units below pKA = totally ionised

Question 16

if we have a low pKA - what strength is this base?

Answer 16

Weak base

Question 17

are acids mainly unionised or ionised in acidic conditions?

Answer 17

unionised

Question 18

are acids mainly unionised or ionised in basic environments?

Answer 18

ionised

Question 19

what is the partitioning coefficient log P?

Answer 19

By determining log P of a drug we can assess the tendency of a drug to enter and leave the cell membrane

Question 20

What is the log P equation?

Answer 20

log p = concentration of same species in organic solvent / concentration of same species in water

Question 21

in partitioning coefficient - what is the organic phase usually?

Answer 21

n-octanol (oily) - a good mimic of a biological membrane

Question 22

what if the logP of a molecule is 0?

Answer 22

the molecule equally partitions between aqueous and organic phases.

Question 23

what are the logP values usually between?

Answer 23

6 and -6

Question 24

what does a high log P mean?

Answer 24

generally more oil soluble - it does not necessarily mean the drug is very oil soluble - but rather it could mean that it may not be very soluble in either oil or water, or moree soluble in oil than water

Question 25

What factors affect the solubility of a drug in solution?

Answer 25

1. particle size
2. melting point and boiling point (solid/liquid)
3. molecular size
4. nature and position of chemical head group
5. temperature
6. crystal properties (polymorphic, solvates, amorphous forms)
7. pH

Question 26

What is the passive diffusion ability of -

small non polar hydrophobic molecules

Answer 26

oxygen, nitrogen, benzene cross membranes rapidly

Question 27

What is the passive diffusion ability of - small uncharged polar

Answer 27

CO2, urea, ethanol, water

cross membranes fairly rapidly

Question 28

What is the passive diffusion ability of - large polar

Answer 28

glycerol - pass through membranes less readily

Question 29

What is the passive diffusion ability of - even larger uncharged polar

Answer 29

glucose, sucrose - not really able to pass though membranes

Question 30

What is the passive diffusion ability of - ions

Answer 30

H+, Na+ etc. Cannot pass through membranes passively

Question 31

what are polar solvents?

Answer 31

dissolve ionic solutes and polar substances.
ability of the solute to form hydrogen bonds is important i.e they form hydrogen bonds

water dissolve phenols, alcohols, nitrogen, oxygen
electrolytes
hydrophilic electrolytes

Question 32

what are non polar solvents?

Answer 32

cannot form hydrogen bonds with non electrolytes

dissolve non polar solvents via weak VDW

Question 33

What are the type of interactions that occur when a solute dissolves in a solvent?

Answer 33

ALL non covlalent e.g. hydrogen bonding, ionic, VDW