Lecture 15

Question 1

What is drug release?

Answer 1

the process by which the drug leaves a drug product and is subjected to absorption

Question 2

What is drug release also achieved by?

Answer 2

diffusion

Question 3

what controlls drug release?

Answer 3

the physicochemical properties of the drug, delivery system, biological system and physiological properties of the biological system
E.g. PH of the stomach different from intestine, the Physical properties of some places are not idea for absorption

Question 4

What is the process of drug release?

Answer 4

the drug first has to go from the solid state to the solution and then the drug molecules can diffuse out.
For some liquid drugs, dissolution is not necessary but it still has to diffuse out from the matrix

Question 5

What happens to the flux if the concentration gradient is bigger?

Answer 5

the flux is also bigger

Question 6

what direction does diffusion occur in?

Answer 6

from an area of high concentration to one of low concentration

Question 7

Why do we have many different dosage forms?

Answer 7

we cant directly give the drug powder to the patient as we have to make it useful and easy for the patient to take

Question 8

what are some of the dosage forms we have for drugs?

Answer 8

tablets, capsules, solutions, injections etc

Question 9

what is a dosage form made up of mainly?

Answer 9

the active ingredient + excipients/additives

Question 10

what are exicipients/additives?

Answer 10

the inactive ingredients. e.g. polymers

Question 11

What do we have to consider when making the dosage form?

Answer 11

stability
reliability
predictability
Reproducibility
effectiveness
convenience

Question 12

what are the essential properties of a medicine?

Answer 12

quality
efficacy
safety

Question 13

What do we need to consider when DESIGNING a dosage form?

Answer 13

Portal of drug entry
Physical form of drug product
Design and formulation of product
Method of manufacture: scale up
Various physicochemical properties of drug and excipients
Control and maintenance of the drug product at the target site e.g. Targeting to the colon, bio adhesive

All of this relies on the control of drug release

Question 14

Why is modified drug release used?

Answer 14

It allows a controlled administration of the dose at a desired rate of delivery

we can keep drug concentration in the plasma for longer, and it will be safer as it will achieve an optimal concentration

we can alter the half life so the drug doesnt have to be taken as much

It may also reduce adverse effects

can also lead to enhancement of patient compliance

Question 15

What are some issues with unmodified released drugs?

Answer 15

if it is quickly released, might cause a problem if it overshoots the required concentration for therapeutic benefit

may also have a short half life

Question 16

What are the different types of modified release dosage?

Answer 16

delayed release
repeat action
prolonged release
sustained release
extended release
controlled release

Question 17

What is delayed release?

Answer 17

drug released after a lapse of time and not immediately. E.g. If the drug should not be exposed to acid. We want a delay in the release so that it has passed through the stomach so the environment is not as acidic

Question 18

What is repeat action release?

Answer 18

Individual dose is released as soon as drug is administered and subsequent doses released and intermittent intervals

Question 19

What is prolonged release?

Answer 19

Drug is provided for absorption over a long period of time

Question 20

What is sustained release?

Answer 20

Initial release is sufficient to produce a therapeutic response and then the blood levels maintained by slow release over a period.

Question 21

What is extended release?

Answer 21

Drug is released slowly so that plasma concentrations are maintained over a prolonged period of time

Question 22

What is controlled release?

Answer 22

drug release is designed at a constant rate to provide plasma concentrations which do not vary with time.

Question 23

what makes up the largest portion of the pharmaceutical industry?

Answer 23

controlled release societ

Question 24

Why are polymers used?

Answer 24

Polymers can be used to form a matrix and embed a drug.
This allows us to modify the drug release as desired
We can provide enteric coatings of the drug
It allows us to achieve a targeting deliver

Question 25

How do we control drug release?

Answer 25

layers and heights of polymers

Question 26

What can we design the polymer to do?

Answer 26

We can design the polymer so they are pH sensitive so they can release the drug when the pH changes

Question 27

What is the basis of our use for polymers?

Answer 27

diffusion. We use the polymer to control the release by controlling the drug diffusion. Remember you can change the diffusion rate by changing viscosity We can also encapsulate the drug capsules by using a polymer. (Enteric coatings) The capsule is a membrane which controls the diffusion rate so that the drug is released by control

Question 28

How are polymers chosen?

Answer 28

First we consider the molecular weight, if its bigger, the viscosity will be bigger Polymers are also normally crosslinked. The bigger the degree of cross linking, the slower the diffusion Whether the polymer is in crystal form or not also places a small effect

Question 29

Describe the structure of an osmotic pump

Answer 29

The outside is coated with a drug. When this layer is explosed to water or liquid it causes the drug to give immediate release so the drug is readily absorbed inside there is a similar layer which is semipermeable, this allows water to enter the tablet's core Once water gets in the NaCl gets dissolved, causing the volume to increase. Once the pressure reaches the threshold, this will start to be pumped out. By controlling the size of osmotically active concentration, we can control the release

Question 30

What is a homogenous matrix?

Answer 30

matrix made from polymer which allows the drug to be diluted equally from all directions

Question 31

How are heterogenous matrices formed?

Answer 31

by putting granules together

Question 32

what do heterogenous matrices do to the drug?

Answer 32

it gives the drug a tortuous path which allows us to control the release it also has pores which liquid enters and allows the drug to leach out

Question 33

What are the 3 processes that occur when the polymer matrix (hetergenous matrix) is exposed to the aqueous environment?

Answer 33

1. Water will diffuse in 2. The drug will start dissolution 3. The drug will diffuse out from this channel or pore or from the surface of the homogenous matrix

Question 34

How does a drug behave in a polymer/heterogenous matrix?

Answer 34

Some of the drug will dissolve into molecules. when placed in an aqueoues environment, the dissolved molecles will be first to diffuse out this forms a depletion zone where diffusion continues simultatneously around the matrix we have a static diffusion layer. If we consider perfect sink conditions like our stomach, it is quickly absorbed This means the drug concentration in the environment is quickly reduced to a small concentration Next to the matrix, the maximum concentration it can reach is the solubility. Over time the depletion layer is formed, however some drugs are still solid There's always a boundary. When Continuing the depletion zone, we can see that The matrix decreases with time

Question 35

Why can fick's first law equation be simplified to just Cs/h?

Answer 35

the Cs is much her than the C due to sink conditions, the drug is removed very quickly

Question 36

What is dQ/dT?

Answer 36

the rate of drug released per unit area of exposed surface of the matrix per unit time

Question 37

What is the higuchi equation?

Answer 37

very important the equation is a function of time as time is the only variable in the equation, everything else is constants

Question 38

What does the higuchi equation describe?

Answer 38

drug release: if you have a high concentration of the drug in the matrix, you have quick drug release It describes the release from homogenous polymer matrix type delivery system. It also applies for the release from emulsions, ointments

Question 39

How do you work out the release rate from the higuchi equation?

Answer 39

look at the release amount, measure the drug released to the medium calculate mass and record the mass released convert time to its square root to get a straight line then work out the release rate