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Review Article
WORLD JOURNAL OF PHARMACEUTICAL
Lokhande et al. AND MEDICAL RESEARCH ISSN 2455-3301
World Journal of Pharmaceutical and Medical Research
www.wjpmr.com WJPMR

A REVIEW ON: SUSTAINED RELEASE TECHNOLOGY

Sarika S. Lokhande*, Phalke N. N. and Badadare S. S.

Maharashtra India.

*Corresponding Author: Sarika S. Lokhande

Maharashtra India.

Article Received on 02/09/2019 Article Revised on 23/09/2019 Article Accepted on 14/10/2019

ABSTRACT
Oral drug delivery is the most preferred and expedient option as the oral route provides greatest active surface area
among all drug delivery system for administration of various drugs. The attractiveness of these dosage forms is due
to consciousness to toxicity and ineffectiveness of drugs when administered by oral predictable method in the form
of tablets & capsules. There are several advantages of sustained release drug delivery over conventional dosage
forms like improved patient compliance due to less frequent drug administration, maximum consumption of the
drug, increased safety margin of potent drug, reduction of fluctuation in steady-state drug levels, decrease in
healthcare costs through enhanced therapy and shorter treatment period. The principal goal of sustained release
forms is the improvement of drug therapy assessed by the relationship between advantages and disadvantages of
the use of sustained release system.

KEYWORD: Matrix type system, oral drug delivery system, Conventional dosage form, Mechanism of drug
release, Advantages & disadvantages, bilayer tablet.

INTRODUCTION the system is successful in maintaining constant drug

levels in the blood or target tissue, it is considered as a
All the pharmaceutical products formulated for systemic
controlled-release system.[9]
delivery via the oral route of administration irrespective
of the mode of delivery (immediate, sustained or
controlled release) and the design of dosage forms (either
solid dispersion or liquid), must be developed within the
intrinsic characteristics of GI physiology,
pharmacokinetics, pharmacodynamics and formulation
design is necessary to achieve a systemic approach to the
successful development of an oral pharmaceutical dosage
form.[1-5] compensation of administering a single dose of
a drug that is released over an extensive period of time,
instead of numerous doses, have been obvious to the
Pharmaceutical industry for some time. drug delivery
dosage forms can be traced to the 1938.

patent of Israel Lipowski. This work concerned coated Figure 1: Classification of Modified Release Drug
pallets for extended release of drug and was most Delivery System.[10]
probably forerunner to the development of the coated
particle approach to sustained drug delivery that Advantages of Sustain Release Dosage Forms
introduced in the early 1950s.[6] The novel system of 1. Decrease in frequency of intakes.
drug delivery offer a means of improving the therapeutic 2. Reduce side effects.
effectiveness of included drugs by providing sustained, 3. Uniform release of drug over time.
controlled delivery and / or targeting the drug to desired 4. Enhanced patient compliance.[11]
site.[7] The goal of any drug delivery system is to make
available a therapeutic quantity of drug to the proper site Disadvantages of Sustained Release Drug Delivery
in the body to achieve rapidly and then maintain the 1. Increased cost.
desired drug concentration.[8] Sustained release systems 2. Toxicity due to dose dumping.
include any drug delivery system that achieves slow. 3. Unpredictable and often poor in vitro-in vivo
Release of drug over an comprehensive period of time. If correlation.

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 Lokhande et al. World Journal of Pharmaceutical and Medical Research

4. Risk of side effects or toxicity upon rapid release of 2. Osmotic pressure is rate limiting
contained drug (mechanical failure, chewing or Osmosis is a phenomenon in which the flow of liquid
masticating, alcohol intake). occurs from lower concentration to higher concentration
5. Increased potential for first- pass clearance. through a semi permeable membrane which allows
6. Need for additional patient education and transfer of liquid only. The entire drug is coated with a
counseling.[12] semi permeable membrane with a hole on one end of
tablet made by a laser beam. The gastric fluid penetrates
Objectives of oral sustained released dosage form through the membrane, solubilizes the drug and increases
1. To maintain the concentration of drug at constant the interior pressure which pumps the drug solution out
level for a preferred period of time. of the aperture and releases the drug in gastric
2. To reduce the frequency of doses administrated as environment.[16]
compared to conservative dosage form
3. It should deliver active entity directly to site of Classification of Oral Sustained or Controlled
action, minimizing or eliminating side Release Systems
4. effects.[13] The controlled release systems for oral use are mostly
5. This may necessitate delivery to specific receptors solids and based on dissolution, diffusion or a
or to localization to cells or to definite areas of the combination of both mechanisms in the control of release
body. rate of drug. Depending upon the manner of drug release,
6. The safety margin of potent drugs can be improved. these systems are classified as follows:
7. Incidence of both local and systemic adverse side 1. Continuous release systems
effects can be reduced in sensitive patient.[14] 2. Delayed transit and continuous release systems
3. Delayed release systems.[17]
Various Mechanisms of Medicament Release
1. Diffusion is rate limiting 1. Continuous release systems
Diffusion is heavy force where the movement of drug Continuous release systems release the drug for a
molecules occurs from elevated concentration in the extended period of time along the entire length of
tablet to lesser concentration in gastro intestinal fluids.[15] gastrointestinal tract with normal transportation of the
This movement depends on surface area uncovered to dosage form. The various systems under this category are
gastric fluid, diffusion pathway, drug concentration as follow:
gradient and diffusion coefficient of the system (Fig. 1). A. Diffusion controlled release systems
B. Dissolution controlled release systems
C. Dissolution and diffusion controlled release systems
D. Ion exchange resin- drug complexes
E. pH-independent formulation
F. Osmotic pressure controlled systems.[18]

A. Diffusion controlled release systems[19]

In this type of systems, the diffusion of dissolved drug
through a polymeric barrier is a rate limiting step. The
drug release rate is never zero-order, since the diffusional
path length increases with time as the insoluble matrix is
gradually exhausted of drug. Diffusion of a drug
molecule through a polymeric membrane forms the basis
of these controlled drug delivery systems.

B. Dissolution-controlled release systems[20]

The drug present in such system may be the one Having
elevated aqueous solubility and dissolution rate
Dissolution-controlled release can be obtained by
Figure 2: Diffusion Release Pattern. slowing the dissolution rate of a drug in the GI medium,
incorporating the drug in an insoluble polymer and
In practice, we can follow either of the two methods, coating drug particles or granules with polymeric
a. The drug is formulated in an insoluble matrix; the materials of varying thickness.[24] The rate limiting step
gastric fluid penetrates the dosage form and for dissolution of a drug is the diffusion across the
dissolves the medicament and liberate the drug aqueous boundary layer.
through diffusion.
b. The drug particles are covered with polymer of C. Dissolution and diffusion controlled release
defined thickness so as the portion of drug slowly systems[21]
diffuse through the polymer to maintain constant In such systems, the drug core is encased in a partly
drug level in blood.[15] soluble membrane. Pores are thus created due to

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dissolution of parts of the membrane which permit entry Disadvantage of bilayer tablet
of aqueous medium into the core and hence drug 1. Some drug resist compression into impenetrable
dissolution and allow diffusion of dissolved drug out of compacts, due to amorphous nature, low density
the system. nature.
2. Bilayer rotary presses are expensive.
Formulation strategy for oral SRDDS[22] 3. Bitter testing drugs, drugs with an objectionable
1. Diffusion Sustained System odor or drugs that are sensitive to oxygen
2. Dissolution Sustained System 1. may require encapsulation or coating.
3. Methods using ion exchange 4. Inaccurate individual layer weight control.
4. Methods using osmotic pressure 5. Insufficient hardness, layer separation reduced
5. pH independent formulation yield.[26]
6. Altered density formulation
Homogenous type
Bilayer tablet Bilayer tablets are preferred when the release profiles of
Over 90% of the formulations manufactured today are the drugs are unusual from one another. bilayer allows
ingested orally. This show that this class of formulation for designing and modulating the dissolution and release
is the most accepted worldwide and major attention of characterstics. bilayer tablets are prepared with one layer
the researcher is towards this direction. The most of drug for instant release while second designed to
important aim of sustained drug delivery is to decrease release drug, either as second dose or in an extensive
frequency of dosing. The design of modified release drug release manner.
product are to optimize a therapeutic regimen by
providing slow and continuous delivery of drug over the Heterogeneous type
partial dosing interval providing greater patient Bilayer tablet is appropriate for sequential release of two
compliance and convenience. Bilayer the tablet is the drugs in combination, separate two incompatible
new era for the successful growth of controlled release substances.[27]
formulation.[23]
Need of bilayer tablet
Bi-layer tablets suitable for sequential release of two 1. For the administration of fixed dose combination of
drugs in combination, separate two incompatible different active pharmaceutical ingredient, extend
substances and also for sustained release tablet in which the drug product life cycle, buccal delivery system;
one layer is instantaneous release as initial dose and fabricate novel drug delivery system such as
second layers is maintaince dose there are various chewing device and floating tablet for gastro-
applications of the bi-layer tablets as it consists of retensive drug delivery.
monolithic partly coated or multilayered matrices. 2. Controlling the delivery rate of either single or two
Generally predictable dosage form produce wide ranging different active pharmaceutical Ingredients.[28]
variation in drug concentration in the blood stream and
tissue with unwanted toxicity and poor effectiveness. General properties of bilayer tablet dosage forms
This factor repetitive dosing and unpredictable 1. Bilayer tablet should have elegant product identify
absorption led to concept of controlled drug delivery while free of defect like chips, cracks,
system. The main objective of sustained release drug 2. discoloration and contamination.
delivery is to ensure safety and to improve efficacy of 3. It should have adequate strength to withstand
drugs.[24] mechanical shock during its production, shipping
and dispensing.
Advantages of bilayer tablet 4. It should have chemical and physical stability to
1. Superior chemical and microbial stability compared maintain its physical attributes over time.[29]
to other oral dosage forms.
2. Separation of incompatible component thus Various Approaches Used In the Bilayer Tablet
minimizes physical and chemical incompatiies. 1. Floating drug delivery system
3. Objectionable odor and taste can be masked by 2. Polymeric Bioadhesive system
coating technologies. 3. Swelling system/unfolding system
4. It can be designed in such a manner as to modified
discharge of the layers can be kept as extensive and Types of Bilayer Tablet Press
the other as instant release. A. Single sided tablet press
5. Cost is lesser as compare to other dosage forms. B. Double sided tablet press
6. Suitable for large scale production. C. Bilayer tablet press with displacement
7. Easy to swallowing with least tendency for hang monitoring.[30]
up.[25]

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 Lokhande et al. World Journal of Pharmaceutical and Medical Research

Marketed Preparation of Bilayer Tablets[31]

Sr. no. Product Name Chemical Name Developer
1 ALPRAX PLUS Sertraline, Alprazolam Torrent Pharmaceuticals Ltd.
2 DIAMICRON®XRMEX500 Gliclazide, Metformin Hcl Sedia® Pharmace -uticals Pvt. Ltd
3 DIUCONTIN-K®20/250 Furosemide, Potassium chloride T.C. Health Care Pvt. Ltd.
4 Glycomet®-GP2Forte Metformin hydrochloride, Glimepiride USV Limited
Levocetrizine Hcl,
5 New cold Plus Piramol Healthcare Ltd.
Phenylpropanolamine Paracetamol
Metoprolol succinate, Amlodipine
6 Revelol®-Am 25/5 Ipca Laboratories Ltd.
besilate
7 TRIOMUNE 30 Nevirapine, Lamivudine, Stavudine Cipla Ltd.

Introduction of matrix tablet As the release continues its rate normally decreases with
As sustained release (SR) has given a new. Breakthrough this type of system since the active agent has a
for novel drug delivery system (NDDS) in the field of increasingly longer distance to travel and therefore
pharmaceutical technology. It excludes multifaceted requires a longer diffusion time to release. In these
production procedures such as coating and pelletization systems, the combinations of polymer matrices and
during manufacturing and drug release rate from the bioactive agents chosen must allow for the drug to
dosage form is controlled mainly by the type and diffuse through the pores or macromolecular structure of
proportion of polymer used in the preparations. the polymer upon introduction of the delivery system
Hydrophilic polymer matrix is extensively used for into the biological environment without inducing any
formulating an SR dosage form.[32] change in the 15 polymer itself. Biodegradable polymer
degrades within the body as a result of natural biological
Advantages of SR Matrix DDS processes, eliminating the need to remove a drug
1. The frequency of drug administration is reduced. delivery system after release of the active agent has been
2. Patient compliance can be enhanced. completed.[36]
3. Drug administration can be made more suitable as
well. Most biodegradable polymers are designed to degrade as
4. The blood level oscillation characteristic of multiple a result of hydrolysis of the polymer chains into
dosing of conventional dosage forms is reduced.[33] biologically satisfactory and progressively smaller
5. Better control of drug absorption can be attained, compounds. For some degradable polymers, most
since the high blood level peaks that may be notably the polyanhydrides and polyorthoesters, the
observed after administration of a dose of a high degradation occurs only at the surface of the polymer,
availability drug can be reduce. resulting in a release rate that is proportional to the
6. The characteristic blood level variations due to surface area of the drug delivery system.
multiple dosing of conventional dosage forms can be
reduced. They are initially dry and when placed in the body will
7. The total amount of drug administered can be absorb water or other body fluids and swell. The
reduced, thus maximizing availability with swelling increases the aqueous solvent content within the
minimum dose. Minimize or eliminate local side formulation as well as the polymer mesh size, enabling
effects. Minimize or eradicate systemic side effect. the drug to diffuse through the swollen16 network into
Reduce drug accumulation with chronic dosing.[34] the external environment.[37]

Disadvantages of SR Matrix DDS CONCLUSION

1. Probability of dose dumping.
By the above discussion, it can be easily concluded that
2. Reduced potential for dose adjustment.
sustained-release formulation are helpful in increasing
3. Cost of single unit higher than predictable dosage
the efficiency of the dose as well as they are also
forms.
improving the patient’s compatibility.
4. Increase potential for first pass metabolism.
5. Requirement for additional patient education for
On the other hand, sustained release implies slow release
proper medication.[35]
of drug over a time period. Sustain released formulation
may or may not be controlled release. From the above
General mechanism of drug release from polymer
discussion, we can concluded that development of
There are three primary mechanisms by which active
SRDDS depend upon a variety of factors such as
agents can be released from a delivery system namely;
Biopharmaceutics, Pharmacokinetic and
Diffusion occurs when a drug or other active agent
Pharmacodynamic characteristics of drug. Sustained
passes through the polymer that forms the controlled-
release drug delivery system has leaded no difficulty of
release device. Diffusion occurs when the drug passes
market penetration as replacement of oral predictable
from the polymer matrix into the exterior surroundings.
drug delivery system.

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 Lokhande et al. World Journal of Pharmaceutical and Medical Research

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Gourishankar college of D pharma, Limb Satara for
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