A Review on Novel Osmotically Controlled Drug Delivery System

Vol. 3, No. 2, July-December 2012 97

Corresponding author: E-mail: deepakpharmacist89@yahoo.com
INDIAN JOURNAL OF PHARMACEUTICS
Volume 3 Number 2 July-December 2012 pp. 97-105
I J P
A Review on Novel Osmotically Controlled Drug Delivery System
Sharma Deepak*, Kumar Dinesh, Singh Mankaran, Singh Gurmeet and
Rathore Mahendra Singh
CT Institute of Pharmaceutical Sciences, Shahpur, P.O- Udopur, Near Lambra, Jalandhar -144020
Punjab, INDIA
Abstract: Conventional drug delivery systems are known to provide an immediate release of drug, in which
one can not control the release of the drug and can not maintain effective concentration at the target site for
longer time. Osmotically controlled drug delivery systems (OCDDS) are most promising systems for controlled
drug delivery. Osmotically controlled drug delivery systems utilize osmotic pressure for controlled delivery of
active agents. Various patents are available for osmotic drug delivery system like Rose and Nelson pump,
Higuchi Leeper pump, Higuchi Theeuwes pump, Elementary osmotic pump etc. Various techniques available
for preparation of OCDDS include push pull osmotic pump, Osmotic bursting osmotic pump, Liquid OROS,
Telescopic capsule for delayed release, OROS-CT (colon targeting), and Sandwiched osmotic tablet system.
These systems can be used for systemic as well as targeted delivery of drugs. Drug delivery from these systems,
to a large extent, is independent of physiological factors of GI tract. Release of drug from formulation is depends
on various formulation factors such as solubility of drug, osmotic pressure generated in the system, size of the
drug delivery orifice, nature & thickness of rate controlling membrane. The present review article mainly focus
on the basic components of osmotically controlled drug delivery system, various factors governing drug release
from these systems and types of osmotically controlled drug delivery systems.
Keywords: Osmotic drug delivery system, Formulation factors, Zero order release, Osmotic pressure, Semi
permeable membrane, Controlled release.
INTRODUCTION
Besides the drug itself, the right dosage over time
is crucial for an effective therapy. Rate-controlled
release systems allow maintaining the drug
concentration within the body at an optimum level.
This minimizes the risk of disadvantageous side
effects, poor therapeutic activity, or even adverse
effects. Over the years, a multitude of different
technological approaches addressing this goal have
been developed. However, only few of them
succeeded in becoming cutting edge technologies
applied to versatile therapeutic applications. A very
successful approach for rate controlled drug
delivery is represented by osmotically controlled
drug delivery system
[1]
. Osmotic systems utilize the
principle of osmotic pressure for the delivery of
drugs. Drug release from these systems is
independent of pH and other physiological
parameter to a large extent and it is possible to
modulate the release characteristic by optimizing
the properties of drug and system
[2]
.
Osmosis can be defined as the spontaneous
movement of the solvent from a solution of lower
solute concentration to a solution of higher solute
concentration through an ideal semi
permeablemembrane, which is permeable only to
the solvent but impermeable to the solute. The
pressure applied to the higher concentration side to
inhibit solvent flow is called the osmotic pressure
[3]
.
Osmotic pressure is a colligative property that
depends on the concentration of solute (neutral
molecule or ionic species). Solutions of different
concentrations having the same solute and solvent
system exhibit an osmotic pressure proportional to
Sharma Deepak, Kumar Dinesh, Singh mankaran, Singh Gurmeet and Rathore Mahendra Singh
98 Indian Journal of Pharmaceutics
their concentrations. Thus a constant osmotic
pressure, and thereby a constant influx of water,
can be achieved by an osmotic drug delivery system
that results in a constant release rate of drug.
Therefore, zero-order release, which is important
for a controlled release delivery system when
indicated, is possible to achieve using these systems
[4]
. Drug delivery from these systems, to a large
extent, is independent of the physiological factors
of the gastrointestinal tract and these systems can
be utilized for systemic as well as targeted delivery
of drugs. The release of drugs from osmotic systems
is governed by various formulation factors such as
solubility and osmotic pressure of the core
components, size of the delivery orifice, and nature
of the rate-controlling membrane
[5]
.
Advantages of Osmotically Controlled Drug
Delivery System
[6]
The following advantages have contributed to the
popularity of osmotic drug delivery systems:
The delivery rate of zero-order (which is
most desirable) is achievable with osmotic
systems. Both in vitro and in vivo
experiments have established this fact.
Delivery may be delayed or pulsed, if
desired.
For oral osmotic systems, drug release is
independent of gastric pH and hydro-
dynamic conditions.
Higher release rates are possible with
osmotic systems compared with
conventional diffusion-controlled drug
delivery systems.
The release rate of osmotic systems is highly
predictable and can be programmed by
modulating the release control parameters.
A high degree of in vivoin vitro correlation
(IVIVC) is obtained in osmotic systems.
The release from osmotic systems is
minimally affected by the presence of food
in the gastrointestinal tract (GIT).
Basic Components of Osmotically Controlled
Drug Delivery System
Drug: Drugs which have short biological half-life
and which is used for prolonged treatment are ideal
candidate for osmotic systems. Drug having
following characteristics are suitable for
formulation:
It should have short half-life
Prolonged release of drug should be
desired.
It should be potent in nature.
Solubility of drug should not be very high
or very low
[7]
.
Osmotic agents: Osmotic components usually
are ionic compounds consisting of either inorganic
salts or hydrophilic polymers. Different type of
osmogents can be used for such systems are
categorized as water-soluble salts of inorganic acids
like magnesium chloride or sulfate; lithium, sodium,
or potassium chloride; sodium or potassium
hydrogen phosphate; water-soluble salts of organic
acids like sodium and potassium acetate, magnesium
succinate, sodium benzoate, sodium citrate, sodium
ascorbate; Carbohydrates like mannose, sucrose,
maltose lactose; water-soluble amino acids and
organic polymeric osmogents, etc
[8]
.
Semipermeable membrane: An important part
of the osmotic drug delivery system is the SPM
housing. Therefore, the polymeric membrane
selection is key to osmotic delivery formulation. The
membrane must possess certain performance
criteria such as:
Sufficient wet strength and water
permeability
Should be biocompatible
Rigid and non-swelling
Should be sufficient thick to withstand the
pressure within the device.
Any polymer that is permeable to water but
impermeable to solute can be used as a
coating material in osmotic devices. E.g.
Cellulose esters like cellulose acetate,
cellulose acetate butyrate, cellulose triacetate
and ethyl cellulose and Eudragits
[9]
.
Plasticizers: Plasticizers have a crucial role to
play in the formation of a film coating and its
ultimate structure. Plasticizers increases the
workability, flexibility and permeability of fluids
.generally from 0.001 to 50 parts ofplasticizer or a
mixture of plasticizers are incorporated in to 100
A Review on Novel Osmotically Controlled Drug Delivery System
Vol. 3, No. 2, July-December 2012 99
part of wall forming material. They can change
viscous-elastic behavior of polymers and these
changes may affect the permeability of the
polymeric films. Plasticizers can have a marked
effect both quantitatively and qualitatively on the
release of active materials from modified release
dosage forms where they are incorporated into the
rate-controlling membrane. Some of the plasticizers
used are as below: Polyethylene glycols, Glycolate,
Glycerolate, myristates, Ethylene glycol
monoacetate; and diacetate- for low permeability,
Tri ethyl citrate, Diethyl tartarate or Diacetin- for
more permeable films
[10]
.
Pore Forming Agents: These are the water-
soluble components which play an important role
in the controlled drug delivery systems. When the
dissolution medium comes into contact with the
semipermeable membrane it dissolves the
channeling agent and forms pores on the
semipermeable barrier. Then the dissolution fluid
enters the osmotic system and releases the drug in
a controlled manner over a long period of time by
the process of osmosis. Some examples of pore
forming agents are polyethylene glycol (PEG) 1450,
-mannitol, bovine serum albumin (BSA),
diethylphthalate, dibutylphthalate and sorbitol
[11]
.
Flux-regulating agents: Flux regulating or flux
enhancing agent or flux decreasing agents are
added to the wall forming materials. It assists in
regulating the fluid permeability of flux through
wall. This agent can be preselected to increase or
decrease the liquid flux. They also increase the
flexibility and porosity of lamina. Hydrophilic
substances such as polyethethylene glycols (300 to
6000 Da), polyhydric alcohols, polyalkylene glycols,
and the like improve the flux, whereas hydrophobic
materials such as phthalates substituted with an
alkyl or alkoxy (e.g., diethyl phthalate or dimethoxy
ethylphthalate) tend to decrease the flux. Insoluble
salts or insoluble oxides, which are substantially
water-impermeable materials, also can be used for
this purpose
[12]
.
Wicking agent: A wicking agent has ability to
draw water into the porous network of a delivery
device. A wicking agent is of either swellable or
non swellable in nature. The function of wicking
agent is to carry water to surfaces inside the core of
tablet, thereby creating channels or network of
increased surface area. Material used for wicking
agent includes colloidal silicon dioxide, kaolin,
alumina, sodium laurel sulphate, low molecular
weight poly (vinyl pyrollidone), bentonite etc
[10]
.
Coating Solvents: Solvents suitable for making
polymeric solution that is used for manufacturing
the wall of the osmotic device include inert
inorganic and organic solvents that do not
adversely harm the core and other materials. The
typical solvents include methylene chloride,
acetone, methanol, ethanol, isopropyl alcohol, butyl
alcohol, ethyl acetate, cyclo-hexane, carbon
tetrachloride, and water. The mixtures of solvents
such as acetone-methanol (80:20), acetone-ethanol
(80:20), acetone-water (90:10), methylene chloride-
methanol (79:21), methylene chloride-methanol-
water (75: 22: 3) can be used
[13]
.
Factors Affecting Drug Release Rate from Osmotic
Controlled Devices
Osmotic pressure: Osmotic pressure is one of the
most rate controlling factor that must be optimized
is the osmotic pressure gradient between inside the
compartment and the external environment. The
rate of drug release is mainly depends upon the
atmospheric pressure created by osmogen. The
simplest and most predictable way to achieve a
constant osmotic pressure for constant delivery of
drug is to maintain a saturated solution of suitable
osmotic agent in the compartment. Sometimes
combination of osmotic agents is also used for
desired osmotic pressure
[10]
.
Table 1
Osmotic Pressure of Saturated Solution of Commonly
used Osmogent
[10]
Compound or mixture Osmotic pumpatmospheric
pressure (atm)
Sodium chloride 356
Potassium chloride 245
Fructose 355
Potassium sulphate 39
Mannitol 38
Dextrose-fructose 450
Lactose-sucrose 250
Solubility: The kinetics of osmotic drug release
is directly related to the solubility of the drug within
the core. Assuming a tablet core of pure drug, the
fraction of core released with zero-order kinetics is
given by the following equation.
Sharma Deepak, Kumar Dinesh, Singh mankaran, Singh Gurmeet and Rathore Mahendra Singh
100 Indian Journal of Pharmaceutics
( ) 1
S
F z
P
=
Where F (z) is the fraction released by zero-order
kinetics, S is the drugs solubility (g / cm
3
), and is
the density (g / cm
3
) of the core tablet. Drugs with
a solubility of 0.05 g / cm would be released with
95% zero-order kinetics according to above
equation. However, the zero-order release rate
would be slow, due to the small osmotic pressure
gradient. Conversely, highly water-soluble drugs
would demonstrate a high release rate that would
be zero-order for a small percentage of the initial
drug load. Thus, the intrinsic water solubility of
many drugs might preclude them from
incorporation into an osmotic pump. However, it
is possible to modulate the solubility of drugs
within the core, and thus, extend this technology
for delivery of drugs that might otherwise have
been poor candidates for osmotic delivery. Some
of the approaches that have been used to deliver
drugs having extremes of solubility are:
(a) Use of wicking agents: These agents may
enhance the surface area of drug with the incoming
aqueous fluids. E.g. colloidal silicon dioxide,
sodium lauryl sulfate, etc. Ensotrol.
(b) Resin Modulation approach: Ion-exchange
resin methods are commonly used to modify the
solubility of drugs. Some of the resins used in
osmotic systems are Poly (4-vinyl pyridine),
Pentaerythritol, citric and adipic acids.
(c) Use of swellable polymers: Polymers such
as vinyl acetate copolymer, polyethylene oxide have
uniform swelling rate which causes drug release at
constant rate.
(d) Use of effervescent mixtures: Mixture of citric
acid and sodium bicarbonate which creates
pressures in the osmotic system and ultimately
controls the release rate.
(e) Use of cyclodextrin derivatives: They are
known to increase solubility of poorly soluble
drugs. The same phenomenon can also be used for
the osmotic systems.
(f) Use of alternative salt form: Change in salt
form of drug may change solubility, as was reported
for oxprenolol. It was found that hydrochloride salt
of oxprenolol was too soluble to maintain a
saturated solution and hence zero order delivery
for the anticipated delivery life of dosage form.
Subsequently succinate salt was found to have
optimum solubility, and osmotic pump was
formulated with this salt form that give extended
release up to 24 h.
(g) Use of encapsulated excipients: Solubility
modifier excipient used in form of mini-tablet
coated with rate controlling membrane.
(h) Use of crystal habit modifiers: Different
crystal form of the drug may have different solubility,
so the excipients which may change crystal habit of
the drug can be used to modulate solubility.
(i) Co-compression of drug with excipients:
Different excipients can be used to modulate the
solubility of drugs with different mechanisms like
saturation solubility, pH dependent solubility.
Examples of such excipients are organic acids,
buffering agent, etc
[14]
.
Orifice size: To achieve an optimal zero-order
delivery profile, the cross-sectional area of the
orifice must be smaller than a maximum size to
minimize drug delivery by diffusion through the
orifice. Furthermore, the area must be sufficiently
large, above a minimum size to minimize
hydrostatic pressure buildup in the system. The
typical orifice size in osmotic pumps ranges from
600 to 1 mm. Methods to create a delivery orifice
in the osmotic tablet coating are:
Mechanical drill.
Laser drill: This technology is well
established for producing sub-millimeter
size hole in tablet. Normally CO
2
laser beam
(with output wavelength of 10.6) is used
for drilling purpose.
Indentation that is not covered during
coating process. Indentation made in core
tablet by using modified punches having
needle on upper punch.
Use of leachable substances in the
semipermeable coating: e.g. controlled
porosity osmotic pump.
Use of leachable substances in the semi
permeable membrane coating. e.g.
controlled porosity osmotic pump
[15]
.
Thickness of membrane: A principle factor
controlling the rate of penetration of water into the
dispenser is the thickness of the membrane. The
A Review on Novel Osmotically Controlled Drug Delivery System
Vol. 3, No. 2, July-December 2012 101
permeability of water into the membrane can be
enhanced by the choice of a suitable type of the
membrane material. The time of release of the active
constituent can be easily varied by as much as 1000
fold based upon the thickness of the membrane. In
general the rate of drug release can be achieved by
varying the membrane material, while small change
up to a five percent can be best achieve by varying
the thickness of the membrane.
Type and amount of plasticizer: In
pharmaceutical industry coatings, plasticizers &
low molecular weight diluents are added to modify
the physical properties and improve film forming
characteristic of polymers. The plasticizers can turn
a hard and brittle polymer into a softer, more pliable
material & make it more resistant to mechanical
stress. The polymer can affect the permeability of
the polymer films can result in the rate of change
of drug release from the osmotic tablets
[16]
.
CLASSIFICATION OF OSMOTICALLY
CONTROLLED DRUG DELIVERY SYSTEM
[7] [15] [17]
Oral Osmotic Drug Delivery System
Single chamber osmotic pump: Elementary
osmotic pump
Multi-chamber osmotic pump: Push pull
osmotic pump, Osmotic pump with non
expanding second chamber
Implantable Osmotic Drug Delivery System
Rose and Nelson pump
Higuchi Leeper pump
Higuchi Theeuwes pump
Miscellaneous
Controlled porosity osmotic pump
Osmotic bursting osmotic pump
Liquid OROS
Telescopic Capsule for Delayed Release
OROS-CT (colon targeting)
Sandwiched osmotic tablet system
Oral Osmotic Drug Delivery System
Single Chamber Osmotic Pump
(a) Elementary osmotic pump: Elementary
osmotic pump shown in Figure 1 was invented by
Felix Theeuwes in 1974 and it essentially contains
an active agent having a suitable osmotic pressure;
it is fabricated as a tablet coated with semi
permeable membrane, usually cellulose acetate. A
small orifice is drilled through the membrane
coating. When this coated tablet is exposed to an
aqueous environment, the osmotic pressure of the
soluble drug inside the tablet draws water through
the semi permeable coating and a saturated aqueous
solution of drug is formed inside the device. The
membrane is non extensible and the increase in
volume due to imbibition of water raises the
hydrostatic pressure inside the tablet, eventually
leading to flow of saturated solution of active agent
out of the device through a small orifice. Though
60-80% of drug is released at a constant rate from
the EOP, a lag time of 30-60 minute is observed in
most of the cases as the system hydrates before zero
order delivery from the system begins. These
system are suitable or delivery of drugs having
moderate water solubility
[18]
.
Figure 1: Elementary Osmotic Pump
Multi-chamber Osmotic Pump
(a) Push Pull osmotic pump: Push-pull osmotic
pump shown in Figure 2, which is a bilayer tablet
and is suitable for the delivery of highly or poorly
water-soluble drugs. The upper layer consists of a
drug along with osmotic agents. The lower layer
consists of polymeric osmotic agents. The tablet is
coated with a semi-permeable membrane, and a
delivery orifice is created similar to that of an
EOP
[19]
.
(b) Osmotic pump with non expanding second
chamber: The second category of multi-chamber
devices comprises system containing a non-
expanding second chamber. This group can be
divided into two sub groups, depending on the
function of second chamber. In one category of these
Sharma Deepak, Kumar Dinesh, Singh mankaran, Singh Gurmeet and Rathore Mahendra Singh
102 Indian Journal of Pharmaceutics
devices, the second chamber is used to dilute the
drug solution leaving the devices. This is useful
because in some cases if the drug leaves the oral
osmotic devices a saturated solution, irritation of
GI tract is a risk. This type of devices consist of two
rigid chamber, the first chamber contains a
biologically inert osmotic agent, such as sugar or a
simple salt like sodium chloride, the second
chamber contains the drug. In use water is drawn
into both the chamber through the surrounding
semi permeable membrane. The solution of osmotic
agent formed in the first chamber then passes
through the connecting hole to the drug chamber
where it mixes with the drug solution before exiting
through the micro porous membrane that form a
part of wall surrounding the chamber. The device
could be used to deliver relatively insoluble drugs
[15] [20]
.
Implantable Osmotic Drug Delivery System
(a) Rose and Nelson Pump: Rose and Nelson, the
Australian scientists, were initiators of osmotic drug
delivery. In 1955, they developed an implantable
pump, which consisted of three chambers: a drug
chamber, a salt chamber contains excess solid salt,
and a water chamber. The drug and water chambers
are separated by rigid semipermeable membrane.
The difference in osmotic pressure across the
membrane moves water from the water chamber
into the salt chamber. The volume of the salt
chamber increases because of this water flow, which
distends the latex diaphragm separating the salt and
drug chambers, there by pumping drug out of the
device
[21]
.
(b) Higuchi Leeper Pump: The Higuchi-Leeper
pump is modified version of Rose-Nelson pump. It
has no water chamber, and the device is activated
by water imbibed from the surrounding
environment. The pump is activated when it is
swallowed or implanted in the body. This pump
consists of a rigid housing, and the semipermeable
membrane is supported on a perforated frame. It
has a salt chamber containing a fluid solution with
excess solid salt. Upon administration/
implantation, surrounding biological fluid
penetrates into the device through porous and
semipermeable membrane and dissolves the
MgSO
4
, creating osmotic pressure inside the device
that pushes movable separator toward the drug
chamber to remove drug outside the device. It is
widely employed for veterinary use. This type of
pump is implanted in body of an animal for delivery
of antibiotics or growth hormones to animals
[8] [22]
.
Figure 2: Push Pull Osmotic Pump
Figure 3: Rose and Nelson Pump
Figure 4: Higuchi Leeper Osmotic Pump
(c) Higuchi Theeuwes pump: Further simplified
variant of Rose-Nelson pump was developed by
Higuchi and Theeuwes. This pump comprises a
rigid, rate controlling outer semipermeable
membrane surrounding a solid layer of salt coated
on the inside by an elastic diaphragm and on the
outside by the membrane. In use, water is
osmotically drawn by the salt chamber, forcing drug
from the drug chamber
[23]
.
A Review on Novel Osmotically Controlled Drug Delivery System
Vol. 3, No. 2, July-December 2012 103
Miscellaneous
(a) Controlled porosity osmotic pump: It is an
osmotic tablet wherein the delivery orifices (holes)
are formed in situ through leaching of water soluble
pore-forming agents incorporated in
semipermeable membrane (SPM) (e.g., urea,
nicotinamide, sorbitol, etc.). Drug release rate from
CPOP depends on various factors like coating
thickness, solubility of drug in tablet core, level of
leachable pore-forming agent(s) and the osmotic
pressure difference across the membrane
[24] [25]
.
surrounded with the barrier layer, the osmotic layer,
and the release rate-controlling membrane. A
delivery orifice is formed through these three layers.
When the system is in contact with the aqueous
environment, water is imbibed & results in the
development of hydrostatic pressure inside the
system forcing the liquid formulation to break
through the hydrated gelatin capsule shell at the
delivery orifice
[23]
.
Figure 5: Higuchi Theeuwes Pump
Figure 6: Controlled Porosity Osmotic Pump
(b) Osmotic bursting osmotic pump: This
system is similar to an EOP expect delivery orifice
is absent and size may be smaller. When it is placed
in an aqueous environment, water is imbibed and
hydraulic pressure is built up inside until the wall
rupture and the content are released to the
environment. Varying the thickness as well as the
area the semipermeable membrane can control
release of drug. This system is useful to provide
pulsated release
[26]
.
(c) Liquid OROS: Liquid OROS controlled
release systems are designed to deliver drugs as
liquid formulations. Liquid API formulation is
present in a soft gelatin capsule, which is
Figure 7: Liquid OROS Soft Capsule
(d) Telescopic Capsule for Delayed Release: This
device consists of two chambers, the first contains
the drug and an exit port, and the second contains
an osmotic engine. A layer of wax like material
separates the two sections. To assemble the delivery
device, the desired active agent is placed into one
of the sections by manual or automated fill
mechanism. The bilayer tablet with the osmotic
engine is placed into a completed cap part of the
capsule with the convex osmotic layer pointed in
to the closed end of the cap and the barrier into the
closed end of the cap and the barrier layer exposed
towards the cap opening. The open end of the filled
vessel is fitted inside the open end of the cap, and
the two pieces are compressed together until the
cap, osmotic bilayer tablet and vessel fit together
tightly. As fluid is imbibed the housing of the
dispensing device, the osmotic engine expand and
exerts pressure on the slid able connected first and
second wall sections. As a result, the net flow of
environmental fluid driven by the pressure enter
the reservoir is minimal and consequently no agent
is delivered for the period
[27]
.
(e) OROS-CT: OROS-CT is used as a once or
twice a day formulation for targeted delivery of
drugs to the colon. The OROS-CT can be a single
osmotic agent or it can be comprised of as many as
five to six push pull osmotic unit filled in a hard
gelatin capsule. After coming in contact with the
gastric fluids, gelatin capsule dissolved and the
Sharma Deepak, Kumar Dinesh, Singh mankaran, Singh Gurmeet and Rathore Mahendra Singh
104 Indian Journal of Pharmaceutics
enteric coating prevents entry of fluids from
stomach to the system as the system enters into the
small intestine the enteric coating dissolves and
water is imbibed into the core thereby causing the
push compartment to swell. At the same time
flowable gel is formed in the drug compartment,
which is pushed out of the orifice at a rate, which is
precisely controlled, by the rate of water transport
across the semi permeable membrane
[15] [16]
.
CONCLUSION
In recent years, novel drug delivery system (NDDS)
has been recognized as an attractive niche for the
pharmaceutical and health industry. Osmotically
controlled drug delivery system utilizes the
principles of osmotic pressure for delivery of drugs
in oral as well as parenteral routes of
administration. Major advantages of these systems
are controlled drug release by zero order. The
osmotically controlled drug delivery system mainly
deliver drug at predetermined rate, independent of
physiological parameter such as food intake, patient
age, and pH of GI tract. The release of drugs from
these types of systems is affected by various
formulation factors such as solubility and osmotic
pressure of the core components, membrane
characteristics, and size of the delivery orifice. Most
of the osmotically controlled drug delivery system
device is designed by modifying the Rose-Nelson
pump and Higuchi-Theeuwes pump. Recent
advances include the development of the controlled
porosity osmotic pump, L-OROS pump and
sandwiched osmotic tablet. The simplicity of
manufacture and opportunities for innovation
make osmotically controlled system, the promising
drug delivery system in the field of prolonged drug
release. In future, there will be increased acceptance
of osmotically controlled drug delivery systems in
pharmaceutical field.
REFERENCES
[1] Herrlich S., Spieth S., Messner S., Zengerle R. Osmotic
Micropumps for Drug Delivery. Adv. Drug Deliv. Rev.
2012: 1-11.
[2] Theeuwes F., Swanson D. R., Guitttard G., Ayer A.,
Khanna S. Osmotic Delivery Systems for the -
Adrenoceptor Antagonists Metoprolol and Oxprenolol:
Design and Evaluation of Systems for Once-daily
administration. Br. J. Clin. Pharmacology. 1985; 19, 69-76.
Figure 8: Telescopic Capsule
Figure 9: OROS-CT
(f) Sandwiched osmotic tablet system (SOTS):
In sandwiched osmotic tablet (SOTS), a tablet core
consisting of a middle push layer and two attached
drug layers is coated with a SPM. As seen in Fig.
10, both the drug layers are connected to the outside
environment via two delivery orifices (one on each
side). After coming in contact with the aqueous
environment, the middle push layer containing
swelling agents swell and the drug is released from
the delivery orifices. The advantage with this type
of system is that the drug is released from two
orifices situated on two opposite sides of the
tablet thus can be advantageous in case of drugs
which are prone to cause local irritation of gastric
mucosa.
Figure 10: Sandwiched Osmotic Tablet System (SOTS)
A Review on Novel Osmotically Controlled Drug Delivery System
Vol. 3, No. 2, July-December 2012 105
[3] Chandy A., Jharia M., Manigauha A. Fabrication and
Evaluation of Osmotic Capsular Pump for Controlled
Drug Delivery. Int. J. Pharm. Pharm. Sci. 2010; 2(1): 99-
103.
[4] Khavare N. B., Dasankoppa F. S., Najundaswamy N.
G. A Review on Key Parameters and Components in
Designing of Osmotic Controlled Oral Drug Delivery
Systems. Indian J. Novel Drug Deliv. 2010; 2(4): 122-131.
[5] Shokri J., Ahmadi P., Rashidi P., Nokhodchi A.
Swellable Elementary Osmotic Pump (SEOP): An
Effective Device for Delivery of Poorly Water-soluble
Drugs. Eur. J. Pharm. Biopharm. 2008; 68: 289297.
[6] Kaushal A. M., Garg S. An Update on Osmotic Drug
Delivery Patents. Pharmaceutical Technology. 2003.
[7] Nikam P. H., Kareparamban J. A., Jadhav A. P., Kadam
V. J. Osmotic Pump: A Reliable Drug Delivery System.
Res. J. Pharm. Bio. Chem. Sci. 2012; 3(3): 478-493.
[8] Singla D. Hari Kumar S. L., Nirmala. Osmotic Pump
Drug Delivery- A Novel Approach. Int. J. Res. Pharm.
Chem. 2012; 2(2): 661-670.
[9] Mane S. S., Kamble M. S., Chaudhari P. D., Bhosale A.
V. An Overview on Oral Osmotically Controlled Drug
Delivery System. Int. J. Universal Pharm. Life Sci. 2012;
2(2): 19-36.
[10] Parashar B., Maurya B., Yadav V., Sharma L. A Review
on Osmotically Regulated Devices. The Pharma
Innovation. 2012; 1(4): 48-56.
[11] Prajapati H. M., Prajapati S. T., Patel C. N. A Review
on Recent Innovation in Osmotically Controlled Drug
Delivery System. Int. J. Pharm. Res. Biosci. 2012; 3: 158-
194.
[12] Wong P. S. L., Edgen D. E., Dong L. C., Dove C. P.,
Inventors; ALZA Corporation, Palo Alto, CA, Assignee.
Controlled Release Liquid Active Agent Formulation
Dosage Forms. US Patent 6596314. 2003.
[13] Keraliya R. A., Patel C., Patel P., Keraliya V., Soni T.
G., Patel R. C., Patel M. M. Osmotic Drug Delivery
System as a Part of Modified Release Dosage form.
International Scholarly Research Network. 2012: 1-9.
[14] Verma R. K., Krishna D. M., Garg S. Formulation
Aspects in the Development of Osmotically Controlled
Oral Drug Delivery Systems. J. Cont. Rel. 2002; 79: 7
27.
[15] Patel H., Patel U., Kadikar H., Bhimani B., Daslaniya
D., Patel G. A Review on Osmotic Drug Delivery
System. Int. Res. J. Pharm. 2012; 3(4): 88-94.
[16] Ghosh T., Ghosh A. Drug Delivery through Osmotic
Systems An Overview. J. Applied Pharm. Sci. 2011; 01
(02): 38-49.
[17] Gupta S., Singh R. P., Sharma R., Kalyanwat R.,
Lokwani P. Osmotic Pumps: A Review. Int. J.
Comprehensive Pharm. 2011; 2(06): 1-8.
[18] Theeuves F. Elementary Osmotic Pump. J. Pharm. Sci.
1975; 64: 1987-1991.
[19] Verma R. K., y Garg S. Current Status of Drug Delivery
Technologies and Future Directions. Pharmaceutical
Technology. 2001; 25(2): 114.
[20] Srenivasa B., Kumar N. R., Murthy KVR. Development
and in Vitro Evaluation of Osmotically Controlled Oral
Drug Delivery System. Eastern Pharm. 2000; 22.
[21] Li X., Jasti B. R. Osmotic Controlled Drug Delivery
Systems, In: Design of Controlled Release of Drug
Delivery Systems, McGraw Hill, 2006; 203-229.
[22] Higuchi T. Osmotic Dispenser with Collapsible Supply
Container. US Patent No. 3, 760,805, 1973.
[23] Thorat M. S., Sapkale A. P., Prasad V. R., Singh C. M.
Overview of Past and Current Osmotic Drug Delivery
Systems. Int. J. Pharm. Chem. Sci. 2012; 1(3): 743-753.
[24] Haslam J. L., Rork G. S. Controlled Porosity Osmotic
Pump, U. S. Patent No. 4880631, 1989.
[25] Liu L., Ku J., Khang G., Lee B., Rhee J. M., Lee H. B.
Nifedipine Controlled Delivery by Sandwiched
Osmotic Tablet System. J. Control Rel. 2000; 68(2): 145-
146.
[26] Theuwes F., Wong P. S. L., Burkoth T. L., Fox D. A.,
Bicek P. R.; (ed) In: Colonic Drug Absorption
and Metabolism, Marcel Decker, New York, 1993, 137-
158.
[27] Santus G., Banker R. W. Osmotic Drug Delivery: A
Review of Patent Literature. J. Control Rel. 1995; 35: 1-
21.