Controlled Release Drug Delivery Systems Flashcards
What are conventional release dosage forms also known as?
Immediate release dosage form
What is conventional drug release?
This is a form of dosage preparation which shows a release of active substance not deliberately modified by special formulation design or manufacturing method.
In the case of a solid dosage form the dissolution profile of the active substance depends essentially on its intrinsic properties.
What is disintegration?
The break up of solid dosage form into primary powder particles
What factors affect dissolution and solubility?
Physiological factors: Presence of food Surfactant levels in gastric juice and bile salts Agitation Concentration of drug in GI fluids
Drug/formulation factors:
Surface area and particle size
Solubility in pH in the diffusion layer (and pKa)
Salt form
Crystal form (polymorphism, amorphous, solvates)
Which factors will not be focused on?
Lipid solubility and permeability which govern absorption.
We will only focus on factors which affect the release of drug from the dosage form
What are limitations of conventional release dosage forms?
Fluctuating plasma concentrations
Potential for periods of toxic concentration
Potential for periods of sub-therapeutic concentration
Dosing is often related to half life, so drugs with short half life require frequent dosing which decreases patient compliance
What is a modified release dosage form?
A peparation where the rate and/or place of release of active substance is different from that of a conventional release dosage form administered by the same route.
This is achieved by special formulation design or manufacturing method
This includes controlled release, long acting, CD, extended release, MR and pulsatile release forms.
What are the main intrinsic properties which govern release forms of drugs?
Dissolution and disintegration
What factors affect dissolution?
Factors in the NW equation including
Diffusion coefficient of drug in solution in GIT
Effective surface area of drug particles in contact with GI. Fluids
Thickness of diffusion layer around each drug particle
Saturation solubility of drug in diffusion layer
Concentration of the drug in GI fluids
What is agitation..
A stagnant layer may form around particles and/or in the GIT
Therefore, based on the motility of intestine there can be changes in the thickness of the stagnant layer which can change the rate of dissolution. e.g. concentration of drug in GI fluids.
What is the concept of controlled release?
Needed a solution to overcome the need for frequent dosing.
Delivery systems have since been developed which continuously release small amounts of drug over an extended period of time at a predetermined rate to prolong the therapeutic effect.
How are controlled release drugs achieved?
By incorporating additives into the formulation which slow down the release of drug from the formulation
What is the ultimate result of controlled release drugs?
To achieve steady state plasma levels which last for a prolonged period of time
What is controlled drug delivery?
The delivery of the drug at a rate and/or a location indicated by the needs of the body or disease state over a specified period of time:
What are the types of controlled drug delivery?
Temporal delivery, spatial delivery or a combination of the above
What is temporal delivery?
Control over the rate of drug release e.g. Delayed or constant
What is spatial delivery?
Control over the location of drug release e.g. Localised delivery vs. Targeting systems
What are the advantages of controlled drug delivery?
Increased patient compliance
=less frequent administration
=less invasive treatment
=more convenient
Less total drug required
=minimises local and systemic side effects
=decreases drug accumulation with chronic use
Improve efficiency in treatment
=cure or control condition more promptly
=improve control by reduction in fluctuation
=may improve bioavailability
More economical
=less cost of drug, hospitalisation, side effects, etc
What are the potential limitations of controlled release drug delivery systems?
Variable bioavailability due to physiological factors, pH, enzymes, transit rates, food, diseases and other drugs
Limitations on duration of action. (Oral=12 hours + time that the absorbed drug continues to exert its reaction)
Products designed to remain intact may become lodged in some site in the GIT leading to irritation or dose dumping
Usually costs more per unit dose
What are the controlled release types we will focus on?
Matrix systems
Membrane controlled systems
Osmotic pump systems
Intrinsically conducting polymer systems
What are matrix systems?
Contain drug dispersed in polymer matrix (can be hydrophilic or hydrophobic)
How is drug release controlled in matrix systems?
By diffusion.
How do hydrophilic colloid matrices work?
These matrices are riding systems. The drug becomes available as the matrix dissolves.
The rate of drug release is controlled by the dissolution of the matrix
How do lipid/insoluble polymer matrices work?
These are non eroding matrices.
The drug becomes available as the solvent enters the matrix and dissolves the drug.
The rate of drug else is controlled by fluid penetration.
