Sustained and controlled release systems
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
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