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.
What are the types of eroding systems?
Bulk eroding
Surface eroding
Are eroding systems biodegradable?
Yes
What is an example of an erodible matrix?
Sinemat. This is controlled release.v
Can you halve a tablet? (Of matrix systems)
Yes
What is an example of a non erodible matrix?
Duride.
As it is non erodible, the patient may notice the matrix in their faeces following oral delivery as the drug dispersed in the polymer will be released, leaving the remaining polymer ghost to journey through the GIT
What are membrane controlled systems?
A type of reservoir system where the drug is contained within a reservoir
The rate controlling step is the diffusion of the drug through the membrane.
Dose pumping = potential concept which must be considered
What is an example of a membrane controlled system?
Estraderm TTS which contains estradiol in the reservoir for the transdermal delivery of the drug.
This is used for hormone replacement therapy
What are the components of the membrane controlled system?
Backing film, Drug reservoir formation Release controlling membrane Adhesive Protective liner
What are osmotic pump systems?
Where the drug is included in the water soluble core.
This core is coated in a semi permeable membrane to allow the passage of water.
If water is present in hype surrounding environment it will enter the core resulting in an increased hydrostatic pressure. This will force the drug out of a hole drilled in the coating
What are the components of the osmotic pump system?
Drug containing core
Semi permeable membrane
Laser drilled office
Water enters the system, and causes the drug to be released through the office
What are smart materials?
Aka intelligent or stimuli responsive materials
These can respond to endogenous or exogenous stimulants
What endogenous stimulants can smart materials respond to?
Enzymes
PH
Ionic strength
Specific species
What exogenous stimuli can smart materials respond to?
Electric field
Magnetic field
Ultrasound
Temperature
What is the rationale behind controlled release systems?
To allow drug delivery on demand or as needed
Allow flexibility over the dose delivered
Able to terminate drug release if required
Optimising benefit to side effect ratio
Effective therapy for chronic disease state
Improved patient adherence to treatment
What are intrinsically conducting polymers?
Traditional carbon based polymers regarded as insulators.
Are conductive and electro active
A combination of electrical properties of metals and mechanical properties of plastics
What are the applications of intrinsically conducting polymers?
Light emitting devices Electromagnetic shielding Artificial muscles Sensing devices Corrosion inhibitors Functional coatings
Can be applied to drug delivery as stimuli responsive materials
What can electroactivity of an intrinsically conducting polymer be used for?
Alter electrostatic charge, volume and hydrophilic/lipophilic balance.
Can be exploited for drug delivery.
What is the example of the ICP used for drug delivery purposes?
Polypyyrole
How is Resperidone normally adminstered?
As an IM injection every 2 weeks.
What is resperidone used for?
It is the only oral atypical antipsychotic available in NZ
Why is resperidone used?
It benefits patients non compliant to oral therapy
What are the limitations of resperidone?
3 week lag time following administration
Severe side effects which can occur at anytime during treatment
Formulation cannot be recalled, dose cannot be altered following administration
Takes 8 weeks for drug to be eliminated from the body
How can the limitations of resperidone be addressed?
By using a stimuli responsive material like a system based on intrinsically conducting polymers.
This would look like a microchip. The idea is that when a dose is required, the patient can just get it by pushing a button.
What is the role of pharmacists in utilising controlled release systems?
Pharmacists in the best position to advise about specific drugs as well as specific delivery systems.
Pharmacists also consult with the patient and other health care professionals regarding specific advice which can be made about the delivery system
