SUSTAINED AND CONTROLLED DRUG DELIVERY SYSTEM: A REVIEW

Sukanya Patil*1
1
*Faculty of Pharmaceutics, H. K. College of Pharmacy, Oshiwara- 400102, Maharashtra, India.
Email ID: [email protected]

ABSTRACT
In order to overcome the drawbacks of conventional drug delivery systems, several technical advancements have led to the
development of controlled drug delivery system that could revolutionize method of medication and provide a number of
therapeutic benefits like multiple dosing and single doses of sustained and controlled delivery formulations. Oral controlled
release drug delivery is a drug delivery system that provides the continuous oral delivery of drugs at predictable and
reproducible kinetics for a predetermined period throughout the course of GI transit and also the system that target the
delivery of a drug to a specific region within the GI tract for either a local or systemic action. Over the past decades an
entirely new technique for the delivery of a drug and other biologically active agents has been developed this technique for
the drug administration is termed Sustained release or controlled release. These tablet owing a twofold or greater reduction
in frequency of administration of a drug in comparison with the frequency required by a conventional dosage form. It is
designed to maintain constant levels of a drug in the patient's bloodstream by releasing the drug over an extended period.
Maintaining constant blood levels of the drug in the bloodstream increases the therapeutic effectiveness of the drug. All the
pharmaceutical products formulated for systemic delivery via the oral route of administration, irrespective of the mode of
delivery (immediate, sustained or controlled release) and the design of dosage form (either solid dispersion or liquid), must
be developed within the intrinsic characteristics of GI physiology.

KEYWORDS
Controlled release drug delivery system (CRDDS), Sustained release drug delivery system (SRDDS), Classification,
Advantages, Disadvantages, Drug design, Polymers used and Market formulations.

INTRODUCTION SUSTAINED RELEASE SYSTEM

Drugs can be administered through various routes; Sustained drug delivery is that type
however, of all the routes of administration, oral route of of system which achieve prolonged therapeutic effect by
administration is the most convenient for administering continuously releasing medication over an extended
and for dosage adjustments. Important reason for their period of time after administration of single dose.
popularity is their convenience of application and the
ease of preparation on an industrial scale [1].
Controlled drug delivery occurs when a polymer is
combined with a drug or active agent such that the
release from the bulk material is pre-designed.
Controlled and Sustained Release, both has been used in
consistent and confusing manner. Both represent
separate delivery process. Sustained release constitutes
any dosage form that provides medication over an
extended time or denotes that the system is able to
provide some actual therapeutic control whether this is
of a temporal nature, spatial nature or both. Sustained
release system generally does not attain zero order type Fig 1: Plasma drug concentration profiles for
release and usually try to mimic zero order release by conventional tablet formulation, a sustained release
providing drug in a slow first order. The basic rationale and a zero-order controlled release formulation.
for controlled drug delivery is to alter the
pharmacokinetics and pharmacodynamics of ADVANTAGES
pharmacologically active moieties by using novel drug • Enhance patient compliance and convenience.
delivery system or by modifying the molecular structure • Reduction in dosing frequency.
and /or physiological parameters [2]. • Reduced fluctuations in circulating drug levels.
• More uniform effect.
CONTROLLED RELEASE SYSTEM • Employ less total drug that will:
Controlled drug delivery is that type • Minimize or eliminates local side effects.
of system which release the medicaments from the • Minimize or eliminates systemic side effects.
dosage form at a predetermined specified rate locally or • Minimize drug accumulation with chronic dosing.
systemically for a specified period of time. • Obtains less potentiating or reduction in drug activity
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on chronic use. AQUEOUS SOLUBILITY
• Safety margin of potent drug is increased by technically Most of the drugs are weak acids or weak bases. Drugs
excellent designing of formulation. [3] with low water solubility will be difficult to incorporate
into SR mechanism. For a drug with high solubility and
Industrial Advantages rapid dissolution rate, it is often quite difficult to retard
• Illustration of innovative /technological its dissolution rate. A drug of high-water solubility can
• Leadership dissolve in water or GI fluid readily and tends to release
• Product life-cycle extension its dosage form in a burst and thus is absorbed quickly
• Product differentiation leading to a sharp increase in the blood drug
• Market expansion concentration compared to less soluble drug. It is often
• Patent extension [4] difficult to incorporate a highly water-soluble drug in the
dosage form and retard the drug release, especially when
DISADVANTAGES the dose is high. The pH-dependent solubility,
• If there requires immediate change during the therapy particularly in the physiological pH range, would be
or if any significant adverse effect is noted and prompt another problem for SR formulation because of the
termination of therapy is needed, Sustained release does variation in the pH throughout the GI tract and variation
not permit immediate termination of therapy. in the dissolution rate [5,6].
• More costly process and equipment are needed in
manufacturing of these dosage forms. The biopharmaceutical classification system allows
• Physician has less flexibility in adjusting dosage estimation of the likely contribution of three major
regimen as this is fixed by design of dosage form. Risk factors which affect the oral absorption.
of dose dumping, usually SRDDS contain drug amount • Solubility
that is 3-4 times more than conventional formulations. • Dissolution and
Sometimes this large quantity of drug may get rapidly • Intestinal permeability.
released leading to toxicity.
• Reduced drug absorption may delay onset of action. Class III (high solubility-low permeability) and Class IV
The effect of food on drug absorption. (low solubility-low permeability) drugs are poor
• Kinetics may differ markedly from one SR candidates for SR dosage form compound with solubility
formulations to another. < 0.1 mg/ml face significant solubilization obstacles and
• Drug absorbed at specific time in GIT cannot be often compounds with solubility 10 mg/ml present
formulated in this type of system. difficulties to solubilization dosing formulation. In
• Increased potential for first pass clearance. general, highly soluble drugs are undesirable for
• For oral effective drug release is influenced and limited formulation into an SR product [7].
by GI residence time.
• These designed for normal population that is on the Table 1: Physicochemical parameters for drug selection
basis of the biological half-lives. Since disease state that
Parameter Preferred value
alters drug dispositions as well as interpatient variability
Molecular weight/size <1000 Daltons
in pharmacokinetics parameters are not accommodated. Solubility >0.1 mg/ml for pH 1-7.8
• Drugs which are acted upon by enzymes in intestine Apparent partition coefficient High
undergo significant enzymatic breakdown as drug Absorption mechanism Diffusion
General absorbability From all GI segments
remains in body for longer time. Release Should not be influenced
• In case of accidental failure of the product effective by pH and enzymes
antidote may be difficult to employ. [3] GI: Gastrointestinal

DRUG SELECTION (FORMULATION PARTITION COEFFICIENT

APPROACHES) The partition coefficient is defined as the fraction of drug
in an oil phase to that of an adjacent aqueous phase.
FACTORS AFFECTING THE FORMULATION Partition coefficient influences not only the permeation
There are two major factors that affect the release rate of the drug across the biological membranes but also
from the DDS. They are: diffusion across the rate controlling membrane or matrix
1. Physicochemical factors between the time when a drug is administered, and when
2. Biological factors it is eliminated from the body, it must diffuse through a
variety of biological membranes that act primarily as
PHYSICOCHEMICAL FACTORS lipid-like barriers. A major criterion in evaluation of the
a. Aqueous solubility ability of a drug to penetrate these lipid membranes (i.e.,
b. Partition coefficient (P [O/W]) its membrane permeability) in its apparent oil or water
c. Drug pKa and ionization at physiological pH partition coefficient defined as,
d. Drug stability K= Co/Cw
e. Molecular weight and diffusivity Where, Co = Equilibrium concentration of all forms of
f. Protein binding g. Dose size. the drug in an organic phase at equilibrium,

2
Cw = Equilibrium concentration of all forms in an system [7].
aqueous phase.
In general, drugs with an extremely large value of K are PROTEIN BINDING
very oil soluble and will partition into membranes quite It is well-known that many drugs bind to plasma proteins
readily. The relationship between tissue permeation and with concomitant influence on the duration of drug
partition coefficient for the drug is generally defined by action. Since blood proteins are four the most part re-
the Hansch correlation, which describe a parabolic circulated and not eliminated, drug protein binding can
relationship between the logarithm of its partition serve as the depot for drug producing a prolonged release
coefficient as shown in Fig. 2 [6,8]. profile, especially if a high degree of drug binding
occurs. The drug interaction and the period of binding
DRUG PKA AND IONIZATION AT with mucin-like protein also influence the rate and extent
PHYSIOLOGICAL PH of oral absorption [10,12,13].
Drugs existing largely in an ionized form are poor
candidates. Absorption of the unionized drugs is well DOSE SIZE
whereas permeation of ionized drug is negligible because For orally administered systems, there is an upper limit
the absorption rate of the ionized drug is 3-4 times less to the bulk size of the dose to be administered. In general,
than that of the unionized drug. The pKa range for an a single dose of 0.5-1.0 g is considered maximal for a
acidic drug whose ionization is pH sensitive is around conventional dosage form. This also holds for sustained-
3.0-7.5 and pKa range for a basic drug whose ionization release dosage forms. Those compounds that require
is pH sensitive is around 7.0-11.0 are ideal for optimum large dosing size can sometimes be given in multiple
positive absorption. Drug shall be unionized at the site to amounts or formulated into liquid system. Another
an extent 0.1-5.0% [7,9]. consideration is the margin of safety involved in the
administration of large amounts of a drug with narrow
therapeutic range [14].

BIOLOGICAL FACTORS
a. Absorption
b. Distribution
c. Metabolism
d. Biological half-life/duration of action
e. Margin of safety/therapeutic index
f. Side effect
g. Disease state.

ABSORPTION
Fig. 2: A relationship between drug action and partition The constant blood or tissue concentration of drug can be
coefficient obtained from the oral SR systems through uniform and
consistent release as well as absorption of the drug. The
DRUG STABILITY desirable quality of the sustaining system is that it should
Drugs undergo both acid/base hydrolysis and enzymatic release completely absorbed. Apparently, the release of
degradation when administered oral route. Drugs that are the drug from the system is the rate limiting step, where
unstable in gastric pH can be developed as slow-release rapid absorption relative to the drug release is always
dosage form and drug release can be delayed until the expected, i.e., Kr << Ka [10].
dosage form reaches the intestine. Drugs that undergo If we assume the transit time of dosage forms in the
gut wall metabolism and show instability in the small absorptive areas of GI tract is about 8-12 hrs, the
intestine are not suitable for SR system. In such case, the maximum half-life for absorption should be
drug can be modified chemically to form prodrugs, approximately 3-4 hrs. Otherwise, the dosage form will
which may possess different physicochemical properties pass out of absorptive regions before drug release is
or a different route of administration should be chosen complete. Therefore, the compounds with lower
[10,11]. absorption rate constants are poor candidates. Some
possible reasons for the low extent of absorption are poor
MOLECULAR WEIGHT AND DIFFUSIVITY water solubility, small partition co-efficient, protein
Diffusivity is defined as the ability of a drug to diffuse binding, acid hydrolysis and metabolism or site specific
through the membrane. Diffusivity depends on size and or dose-dependent absorption. Drugs with the high
shape of the cavities of the membrane. The diffusion co- apparent volume of distribution, which influence the rate
efficient of intermediate drug molecular weight is 100- of elimination of the drugs, are a poor candidate for oral
400 Daltons; through flexible polymer range is 10−6- SR DDS. A drug which extensively metabolizes is not
10−9 cm2 /seconds. Molecular size or weight is suitable for SR DDS. A drug capable of inducing
indirectly proportional to the diffusibility. Drugs with metabolism, inhibiting metabolism, metabolized at the
larger molecular size are a poor candidate for oral SR site of absorption or first-pass effect is the poor candidate

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for this delivery, as it could be difficult to maintain state drug concentration, the zero-order rate of release of
constant blood level. Drugs that are metabolized before a drug from its dosage form is directly proportional to its
absorption, either in the lumen or the tissues of the rate of elimination. Thus, drug with very short half-lives
intestine, can show decreased bioavailability from the require faster rate of release, for a modest duration of
sustained releasing systems [7]. time while dosage form requires large dosage. In general,
drugs with half-lives shorter than 2 hrs are poor
DISTRIBUTION candidates for sustained-release preparations.
The distribution of drug molecules into the tissue and Compounds with long half-lives, more than 8 hrs, are
cells can be the primary factor in particularly drug also generally not used in sustaining forms, since their
elimination kinetics. Since it not only lowers the effect is already sustained [10, 11,12].
concentration of circulating drug, but it also can be rate
limiting in its equilibrium with blood and extravascular MARGIN OF SAFETY/THERAPEUTIC INDEX
tissue. The distribution includes the binding of the drug Margin of safety of a drug can be described by
to the tissues and blood proteins. Protein-bound drugs considering therapeutic index, which is the ration of
molecules are considered as inactive and unable to median toxic dose and median effective dose.
permeate biological membranes, and a high degree of Therapeutic index = TD50/ED50
protein binding provides prolonged therapeutic action. A drug is considered to be relatively safe with
The apparent volume of distribution is one of the therapeutic index more than 10 i.e., larger the ratio the
important parameters of the drugs that describes the more safely is the drug. Margin of the safety of the drugs
magnitude of distribution as well as protein binding determined on the basis of therapeutic index is the range
within the body. The apparent volume of distribution is of plasma concentration in which the drug is considered
the proportionality constant of the plasma concentration to the safe and therapeutically effective. The drugs with
of the drug to the total drug amount in the body. Thus, narrow therapeutic indices the release pattern should be
for the design of sustain release products, one must have more precise to maintain the plasma concentration within
information of the disposition of drug [10,13]. the narrow therapeutic and safety range. The unfavorable
therapeutic index of a drug can be overcome by suitable
METABOLISM employment of the SR mechanisms [10,11].
Metabolism of the drug is either an inactivation of an
active drug or conversion of an inactive drug to an active SIDE EFFECT
metabolite. Metabolism of the drug occurs in a variety of The side effects of some drugs are mainly developed due
tissues, which are containing more enzymes. Drugs that to fluctuation in the plasma concentrations. The
are significantly metabolized before absorption, either in incidences of side effects can be minimized by
the lumen or tissue of the intestine, can show decreased controlling the concentration within therapeutic range at
bioavailability from slower-releasing dosage forms. any given time. The SR drug delivery is the most widely
Most intestinal wall enzyme systems are saturable. As used to incidences of the GI (local) side effects rather
the drug is released at a slower rate to these regions, less than a systemic side effect of the drug. The drug
total drug is presented to the enzymatic process during a properties which induce local or systemic side effect can
specific period, allowing more complete conversion of be circumvented or modified by their incorporation in a
the drug to its metabolites. The formulation of these suitable oral SR delivery system that employs a specific
enzymatically susceptible compounds as prodrugs is controlled release mechanism [10].
another viable solution. Drugs that are capable of either
inducing or inhibiting enzyme synthesis, they are the DISEASE STATE
poor candidate for SR delivery system due to difficulty Disease state and circadian rhythm are not drug
in maintaining uniform blood levels. Drugs possessing properties, but they are equally important as drug
variation in bioavailability due to the first-pass effect or properties in considering a drug for SR.
intestinal metabolism are not suitable for SR DDS For example: -
[10,12]. • Aspirin is a drug of choice for rheumatoid arthritis
though it is not suitable for SR dosage form. Still, aspirin
BIOLOGICAL HALF-LIFE/DURATION OF SR dosage form could be advantageous to maintain
ACTION therapeutic concentrations, particularly throughout the
The usual goal of an oral sustained-release product is to night, thus alleviating morning stiffness.
maintain therapeutic blood levels over an extended • Asthma attacks are commonly occurring before
period. The duration of action significantly influences bedtime, due to a low cortisol level. The highest cortisol
the design of oral SR delivery system and it is dependent level occurred between 12 midnight and 4 a.m. These
on the biological half-life. Factors influencing the variations entail for the design an oral SR delivery in
biological half-life of a drug include its elimination, accordance to circadian rhythm [10,11].
metabolism and distribution patterns. Drugs with short
half-lives required frequent dosing to minimize POLYMERS USED
fluctuations in the blood levels. SR dosage forms would Since the structural and physicochemical characteristics
appear very desirable for such drugs. For a given steady of the polymer are decisive in the drug release

4
mechanism, some will be more suitable than others, Where, D = diffusion coefficient in area/ time dc/dx =
depending on the aim pursued and the drug desired change of concentration 'c' with distance 'x'
[15,16]. Diffusion systems are characterized by release rate of
drug is dependent on its diffusion through inert water
Hydrophilic polymers insoluble membrane barrier. [17,18]
There are basically two types of diffusion devices.
a) Cellulosic
• Methylcellulose (a) Reservoir Type
• Hydroxypropylmethylcellulose (Hypromellose, In the system, a water insoluble polymeric material
HPMC) encloses a core of drug, which controls release rate. Drug
• Hydroxypropylcellulose (HPC) will partition into the membrane and exchange with the
• Hydroxyethylcellulose (HEC) fluid surrounding the particle or tablet. Additional drug
• Ethylhydroxyethylcellulose (E-HEC) will enter the polymer, diffuse to the periphery and
• Sodium carboxymethylcellulose (Na-CMC) exchange with the surrounding media. The polymers
commonly used in such devices are Ethyl cellulose and
b) Non-cellulosic Poly-vinyl acetate.
• Sodium alginate
• Xanthan gum
• Carrageenan
• Chitosan
• Guar gum
• Pectin
• Cross-linked high amylose starch
• Polyethylene oxide
• Homopolymers and copolymers of acrylic acid

Hydrophobic polymers
• Ethyl cellulose
• Hypromellose acetate succinate
Fig 3: Schematic Representation of Reservoir
• Cellulose acetate
Diffusion Controlled Drug Delivery Device
• Cellulose acetate propionate
• Methacrylic acid copolymers
The rate of drug released (dm/dt) can be calculated using
• Polyvinyl acetate
the following equation
Apart from these two types, waxes and insoluble
polymers are also used.

Waxes
Carnauba wax, bees wax, candelilla wax, micro Where, A = Area, D = Diffusion coefficient, K =
crystalline wax, ozokerite wax, paraffin waxes and low Partition coefficient of the drug between the drug core
molecular weight polyethylene. and the membrane, ℓ = Diffusion pathlength and ∆C=
Concentration difference across the membrane.
Insoluble polymers
Ammoniomethacrylate co-polymers (Eudragit RL100, Advantage: By this system Zero order delivery is
PO, RS100, PO), ethyl cellulose, cellulose acetate possible, release rates variable with polymer type.
butyrate, cellulose acetate propionate and latex
dispersion of meth acrylic ester copolymers. Disadvantages: System must be physically removed
from implant sites. Difficult to deliver high molecular
CLASSIFICATION weight compound, generally increased cost per dosage
Based upon the mechanism used for obtaining sustained unit, potential toxicity if system fails. [19,20]
and controlled release of drug, these systems are
classified as follows, (b) Matrix Type
A solid drug is homogenously dispersed in an insoluble
1. Diffusion Controlled System matrix and the rate of release of drug is dependent on the
Basically, diffusion process shows the movement of drug rate of drug diffusion and not on the rate of solid
molecules from a region of a higher concentration to one dissolution.
of lower concentration. The flux of the drug J (in amount
/ area -time), across a membrane in the direction of Advantages: Easier to produce than reservoir or
decreasing concentration is given by Fick’s law. encapsulated devices, can deliver high molecular weight
J= - D dc/dx compounds.

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Disadvantages: Cannot provide zero order release,
removal of remaining matrix is necessary for implanted
system. [21,22]

Fig 5: Encapsulation Dissolution Controlled Systems

Fig 4: Schematic Representation of Monolithic
(matrix) Diffusion Controlled Drug Delivery Device (b) Matrix Dissolution Controlled Systems
In matrix systems the drug is homogeneously dispersed
2. Dissolution Controlled Systems throughout a rate controlling medium. They employ
Drugs having high aqueous solubility and dissolution waxes such as beeswax, carnauba wax, hydrogenated
rate, shows challenge in controlling their dissolution rate. castor oil etc which control drug dissolution by
Dissolution-controlled release can be obtained by controlling the rate of dissolution fluid penetration into
slowing the dissolution rate of a drug in the GI medium, the matrix by altering the porosity of tablet, decreasing
incorporating the drug in an insoluble polymer and its wettability or by itself getting dissolved at a slower
coating drug particles or granules with polymeric rate. The drug release is often first order from such
materials of varying thickness. The rate limiting step for matrices. The wax embedded drug is generally prepared
dissolution of a drug is the diffusion across the aqueous by dispersing the drug in molten wax and solidifying and
boundary layer. The solubility of the drug provides the granulating the same. [26]
source of energy for drug release, which is countered by
the stagnant-fluid diffusional boundary layer. The rate of
dissolution (dm/dt) can be approximated by,

Where, S = Aqueous solubility of the drug. A = Surface

area of the dissolving particle or tablet. D = Diffusivity
of the drug and h = Thickness of the boundary layer.
[23,24]
Fig 6: Schematic Representation of Matrix
(a) Encapsulation Dissolution Controlled Systems Dissolution Controlled Drug Delivery Device
The drug particles are coated or encapsulated by
microencapsulation techniques with slowly dissolving 3. Dissolution and Diffusion Controlled Release
materials like cellulose, poly ethylene glycols, Systems
polymethacrylates, waxes etc. the dissolution rate of The drug core is enclosed in a partially soluble
coat depends upon the solubility and thickness of the membrane. Pores are thus created due to dissolution of
coating. Those with the thinnest layers will provide the parts of the membrane which permit entry of aqueous
initial dose. The maintenance of drug levels at late times medium into the core and hence drug dissolution and
will be achieved from those with thicker coating. [25] diffusion of dissolved drug out of the system. An
example of obtaining such a coating is using a mixture of
ethyl cellulose with poly vinyl pyrrolidiene or
methylcellulose. [27-29]

6
 5. Methods using Ion Exchange
This system is designed to provide the controlled release
of an ionic or ionizable drug. It is prepared by first
absorbing an ionized drug onto the ion-exchange resin
granules such as codeine base with Amberlite, and then
after filtration from the alcoholic medium, coating the
drug resin complex granules with a water permeable
polymer, e.g. a modified copolymer of polyacrylic and
methacrylic ester, and then spray drying the coated
granules to produce the polymer coated drug resin
preparation. The drug is released by exchanging with
appropriately charged ions in the GIT. The drug is then
diffuse out of the resin.
Fig 7: Dissolution and Diffusion Controlled Release
System Resin+ - drug- + X- resin+ - X- + drug-
Where, X- are ions in the GI tract.
4. Water Penetration Controlled Systems
In water penetration-controlled delivery systems, rate The rate of diffusion control by: the area of diffusion,
control is obtained by the penetration of water into the diffusion path length and rigidity of resin.
system. [30] Thus, drug release depends on the ionic environment
(pH, electrolyte conc.) and the properties of resin.
(a) Swelling Controlled Systems Advantage - for those drugs which are highly
Swelling controlled release systems are initially dry and susceptible to degradation by enzymatic processes since
when placed in the body absorbs water or other body it offers a protective mechanism by temporarily altering
fluids and swells. Swelling increases the aqueous solvent the substrate.
content within the formulation as well as the polymer Limitation - The release rate is proportional to the
mesh size, enabling the drug to diffuse through the conc. of the ions present in the vicinity of administration
swollen network into the external environment. [31] site. So variable diet, water intake & intestinal contents
affect the release rate of drug.
(b) Osmotically Controlled Release Systems
These systems are fabricated by encapsulating an They are mainly of 2 types - cation exchange and
osmotic drug core containing an osmotically active drug anion exchange resin.
(or a combination of an osmotically inactive drug with
an osmotically active salt eg NaCl) within a semi Cationic Drugs
permeable membrane made from biocompatible A cationic drug forms a complex with an anionic ion-
polymer, e.g. cellulose acetate. A gradient of osmotic exchange resin e.g. a resin with a SO - group. In the GI
pressure is they created, under which the drug solutes are tract Hydronium ion (H+) in the gastrointestinal fluid
continuously pumped out of tablet through small penetrates the system and activity the release of cationic
delivery orifice in tablet coating over a prolonged period drug from the drug resin complex.
of time through the delivery orifice. This type of drug
system dispenses drug solutes continuously at a zero- H+ + Resin – SO3 - Drug + Resin – SO3 - H+ +
order rate. Release of drug is independent on the Drug+
environment of the system. [32,33]
Anionic Drugs
An anionic drug forms a complex with a cationic ion
exchange resin, e.g. a resin with a [N (CH ) +] group. In
the GI tract, the Chloride ion (Cl-) in the gastrointestinal
fluid penetrates the system and activates the release of
anionic drug from the drug resin complex. [34-36]

Cl- + Resin – [N (CH ) +] - Drug- Resin

– [N (CH ) +] - Cl- + Drug-

6. Chemically Controlled Release Systems

Chemically controlled release systems are the systems
that change their chemical structure, when exposed to
biological fluid. Mostly, biodegradable polymers are
designed to degrade as a result of hydrolysis of the
Fig 8: Schematic Representation of Osmotically
polymer chains into biologically safe and progressively
Controlled Drug Delivery Device

7
smaller moieties. It is of two types and they are Erodible
systems and Pendent chain system.

(i) Erodible Systems: In erodible systems, the

mechanism of drug release occurs by erosion. Erosion
may be two types and they are

Bulk Erosion process polymer degradation may

occur through bulk hydrolysis.
When the polymer is exposed to water hydrolysis
occurs.
Hydrolysis degrades the large polymers into smaller
biocompatible compounds. Fig 10: Pendent chain system
These small compounds diffuse out of the matrix
through the voids caused by swelling. 7. pH– Independent Formulations
Loss of the small compounds accelerates the formation The gastrointestinal tract presents some unusual features
of voids thus the exit of drug molecules. for the oral route of drug administration with relatively
e.g. poly lactide, polyglycolic acid. brief transit time through the gastrointestinal tract, which
constraint the length of prolongation, further the
Surface Erosion process Polymers like chemical environment throughout the length of
polyorthoesters and polyanhydrides etc. occurs gastrointestinal tract is constraint on dosage form design.
degradation only at the surface of the polymer, resulting Since most drugs are either weak acids or weak bases,
in a release rate that is proportional to the surface area of the release from sustained release formulations is pH
the delivery system. dependent. However, buffers such as salts of amino
When the polymer is exposed to water hydrolysis acids, citric acid, phthalic acid phosphoric acid or tartaric
occurs. acid can be added to the formulation, to help to maintain
Hydrolysis degrades the large polymers into smaller a constant pH thereby rendering pH independent drug
biocompatible compounds. release. A buffered controlled release formulation is
These small compounds diffuse from the interface of prepared by mixing a basic or acidic drug with one or
the polymer. more buffering agent, granulating with appropriate
Loss of the small compounds leads to drug loss. pharmaceutical excipients and coating with
Note these polymers do not swell. gastrointestinal fluid permeable film forming polymer.
e.g polyanhydrides. When gastrointestinal fluid permeates through the
membrane, the buffering agents adjust the fluid inside to
suitable constant pH thereby rendering a constant rate of
drug. [38,39]

8. Hydrogels
Hydrogels are water swollen three dimensional
structures composed of primarily hydrophilic polymers.
They are insoluble because of chemical or physical
cross-links. The physical cross-links include crystallites,
entanglements or weak associations like hydrogen bonds
or vander waals forces. These cross- links provide the
physical integrity and network structure. Hydrogels
provide desirable protection of labile drugs, peptides and
proteins. [40,41]

9. Altered Density Formulations

Fig 9: Bulk Erosion and Surface Erosion
Several approaches have been developed to prolong the
residence time of drug delivery system in the
(ii) Pendent Chain System
gastrointestinal tract like High density approach and
Pendent chain systems consist of linear homo or
Low-density approach. [42,43]
copolymers with the drug attached to the backbone
chains. The drug is released from the polymer by
(i) Low density approach
hydrolysis or enzymatic degradation of the linkages.
Zero order can be obtained and the cleavage of the drug
(ii) High density approach
is the rate controlling mechanism. Example for polymers
used in pendent chain systems like n-(2- hydroxy propyl)
methacrylamide etc. [37]

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