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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