Sustained
and controlled release systems
Session Objectives
By the end of this session, students will be able to:
• Define
the terminologies of various modified release dosage forms
• Explain
the need for controlled release dosage forms
• Discuss
the various concepts of controlled release oral dosage forms
History
– The history of controlled release technology is divided
into three time periods
q From
1950 to 1970 was the period of sustain drug release
q From
1970 to 1990 was involved in the determination of the needs of the
control drug delivery
q Post
1990 modern era of controlled release technology
Conventional dosage forms blood level curve
In the conventional therapy aliquot quantities of drugs are
introduced into the system at specified intervals of time with the result that
there is considerable fluctuation in drug concentration level as
indicated in the figure:
Limitations of oral conventional dosage form
• Poor
patient compliance
• Drug
fluctuation can lead adverse effect
• Increased
frequency of drug dosing
Modified release dosage forms blood level curve
However, an ideal dosage regimen would be one, in which the
concentration of the drug, nearly coinciding with minimum effective
concentration (M.E.C.), is maintained at a constant level throughout the
treatment period. Such a situation can be graphically represented by the
following figure
Blood level curve of CDDS
Oral controlled drug delivery system
q Oral
controlled release drug delivery is a system that provides the continuous oral
delivery of drugs at predictable and reproducible kinetics for a predetermined
period throughout the course of GI transit.
q The
system that target the delivery of a drug to a specific region within the GI
tract for either a local or systemic action.
Need for developing controlled drug delivery system
• To
extend the duration of action of the drug
• To
minimize the fluctuations in plasma level
• Improved
drug utilization
• To
reduce the frequency of dosing providing the uniform drug delivery
Differences between controlled release and sustained
release
Controlled drug delivery- which delivers the drug at
a pre-determined rate for a specified period of time.
Controlled release is perfectly zero order release that is the drug
release over time irrespective of concentration.
Sustained release drug delivery system- It includes
any drug delivery system achieves release of drug over an extended period of
time, which not depend on time.
Sustained release implies slow release of the drug
over a time period. It may or may not be controlled release.
Terminologies
Modified Release dosage form
It is defined as one for which the drug release
characteristics of time course and/or
location are chosen to accomplish therapeutic or convenience objectives
not offered by conventional dosage forms
such as solutions, ointments, tablets and capsules.
Delayed Release dosage form
These systems are those that use repetitive, intermittent
dosing of a drug from one or more immediate release units incorporated into a
single dosage form. Examples of delayed release systems include repeat action
tablets and capsules and enteric-coated tablets where timed release is achieved
by a barrier coating.
Extended-release dosage form
A dosage form that allows at least a twofold reduction in
dosage frequency as compared to that drug presented as an immediate release
form
Sustained release dosage form
It is defined as “Any drug or dosage form modification that
prolongs the therapeutic activity of the drug”. This delivery system is
increasingly being used in the treatment of acute and chronic diseases as they
maintain the concentration of drug in plasma above the minimum effective
concentration to and below the minimum toxic level for an extended period of
time.
Plasma drug
concentration of various dosage forms
Merits
Ø Improved
patient convenience and compliance
Ø Reduction
in fluctuation in steady-state level
Ø Increased
safety margin of high potency drug
Ø Maximum
utilization of drug
Ø Less
frequency of dosing
Ø Better
control of drug absorption
Ø Reduction
in health care cost through improved therapy
De merits
Ø Decreased
systemic availability
Ø Poor
invivo – invitro correlation
Ø Possibility
of dose dumping
Ø Less
flexibility in adjusting dosage regimens
Advantages
• Improve
absorption, utilization and thereby enhancing bioavailability
• Decreased
local and systemic side effects reduced gastrointestinal irritation.
• Reduction
in dosing frequency, Reduction in the health care cost.
• Better
patient acceptance and compliance.
• Reduced
fluctuations in circulating drug levels.
• Bioavailability
of certain drugs can be increased
• Night time dosing can be avoided
Commercial /
Industrial Advantages
• Illustration of innovative/technological
leadership
• Product life-cycle extension, Product
differentiation
• Market expansion · Patent extension
Disadvantages
• Dose
dumping.
• Dose
adjustment is difficult. Careful calculation necessary to prevent overdosing
• Patient
education is required for successful therapy.
• Patient
need to substantial additional information as to the proper usage of CRDDS.
• Poor
IVIVC.
• Higher
cost of single unit as compared to cost of single conventional unit.
• Stability
problems.
• Increased
potential for first pass metabolism
• Drug
goes to non-target cells and can cause damage
• Not
all drugs are suitable for formulating into ER dosage form
Summary
• Development
of controlled drug delivery is to extend the duration of action of the drug, minimize the fluctuations in plasma
level ,improved drug utilization and
reduce frequency of drug dosing
• Oral
controlled release drug delivery provides continuous release of drugs at predictable and reproducible kinetics for a
predetermined period throughout the
course of GI transit
• The
limitations of oral controlled release drug delivery system includes decreased systemic availability, poor invivo
– invitro correlation and less
flexibility in adjusting dosage regimens
• Ideal
drug candidate for CRDF includes potent medicament, good margin of safety,
exhibit neither very fast rate of absorption nor excretions
For PDF Notes Click on Download Button
