Flashcards in Lecture 15 Deck (39):
What is drug release?
the process by which the drug leaves a drug product and is subjected to absorption
What is drug release also achieved by?
what controlls drug release?
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
What is the process of drug release?
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
What happens to the flux if the concentration gradient is bigger?
the flux is also bigger
what direction does diffusion occur in?
from an area of high concentration to one of low concentration
Why do we have many different dosage forms?
we cant directly give the drug powder to the patient as we have to make it useful and easy for the patient to take
what are some of the dosage forms we have for drugs?
tablets, capsules, solutions, injections etc
what is a dosage form made up of mainly?
the active ingredient + excipients/additives
what are exicipients/additives?
the inactive ingredients. e.g. polymers
What do we have to consider when making the dosage form?
what are the essential properties of a medicine?
What do we need to consider when DESIGNING a dosage form?
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
Why is modified drug release used?
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
What are some issues with unmodified released drugs?
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
What are the different types of modified release dosage?
What is delayed release?
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
What is repeat action release?
Individual dose is released as soon as drug is administered and subsequent doses released and intermittent intervals
What is prolonged release?
Drug is provided for absorption over a long period of time
What is sustained release?
Initial release is sufficient to produce a therapeutic response and then the blood levels maintained by slow release over a period.
What is extended release?
Drug is released slowly so that plasma concentrations are maintained over a prolonged period of time
What is controlled release?
drug release is designed at a constant rate to provide plasma concentrations which do not vary with time.
what makes up the largest portion of the pharmaceutical industry?
controlled release societ
Why are polymers used?
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
How do we control drug release?
layers and heights of polymers
What can we design the polymer to do?
We can design the polymer so they are pH sensitive so they can release the drug when the pH changes
What is the basis of our use for polymers?
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
How are polymers chosen?
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
Describe the structure of an osmotic pump
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
What is a homogenous matrix?
matrix made from polymer which allows the drug to be diluted equally from all directions
How are heterogenous matrices formed?
by putting granules together
what do heterogenous matrices do to the drug?
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
What are the 3 processes that occur when the polymer matrix (hetergenous matrix) is exposed to the aqueous environment?
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
How does a drug behave in a polymer/heterogenous matrix?
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
Why can fick's first law equation be simplified to just Cs/h?
the Cs is much her than the C due to sink conditions, the drug is removed very quickly
What is dQ/dT?
the rate of drug released per unit area of exposed surface of the matrix per unit time
What is the higuchi equation?
the equation is a function of time as time is the only variable in the equation, everything else is constants
What does the higuchi equation describe?
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