Osmotic systems

DEFINITION:
 Osmosis
 Osmosis is the net movement of solvent molecules
through a partially permeable membrane into a region
of higher solute concentration, in order to equalize the
solute concentrations on the two sides.
 Osmosis refers to the process of movement of solvent
molecules from lower concentration to higher
concentration across a semi permeable membrane.
 Osmotic pressure is the pressure which needs to be
applied to a solution to prevent the inward flow of water
across a semipermeable membrane.

INTODUCTION:
 Osmotic systems utilize the principle of osmosis
and osmotic pressure for the delivery of drugs.
 Drug release from these systems is independent of
pH and other physiological parameter to a large
extent.
 It is possible to modulate the release characteristic
by optimizing the properties of drug and system.

 Osmotic pressure created due to imbibition's of fluid from
external environment into the dosage form regulates the
delivery of drug from osmotic device.
 Rate of drug delivery from osmotic pump is directly
proportional to the osmotic pressure developed due to
imbibition's of fluids by osmogen.
 Osmotic pressure is a colligative property of a solution in
which the magnitude of osmotic pressure of the solution is
independent on the number of discrete entities of solute present
in the solution.
 Hence the release rate of drugs from osmotic dispensing
devices is dependent on the solubility and molecular weight
and activity coefficient of the solute (osmogent).

PRINCIPLES OF OSMOSIS:
 The first report of an osmotic effect dates to Abbenollet {1748}.
 Pfeffer obtained the first quantitative measurement in 1877.
 In Pfeffer experiment a membrane permeable to water but
impermeable to sugar is used to separate a sugar solution from pure
water.
 A flow of water then takes place into the sugar solution that cannot be
halted until a pressure π is applied to the sugar solution.
 Pfeffer showed that this pressure, the osmotic pressure π of the sugar
solution is directly proportional to the solution concentration and the
absolute temperature.
 Within few years, Vant Hoff had shown the analogy between these
results and ideal gas laws by the expression
π = Ø c RT
Where, π = Osmotic pressure, Ø = osmotic coefficient, c = molar
concentration, R = gas constant T = Absolute temperature.

 Osmotic pressure is a colligative property, which depends
on concentration of solute that contributes to osmotic
pressure.
 Solutions of different concentrations having the same
solute and solvent system exhibit an osmotic pressure
proportional to their concentrations.
 Thus a constant osmotic pressure, and thereby a
constant influx of water can be achieved by an osmotic
delivery system that results in a constant zero order
release rate of drug.
 Osmotic pressure for concentrated solution of soluble
solutes commonly used in controlled release formulation
are extremely high ranging from 30 atm for sodium
phosphate up to 500 atm for a lactose-fructose mixture,
as their osmotic pressure can produce high water flow
across semi permeable membrane.

 The osmotic water flow through a membrane is given by the
equation
dvdt = A Q Δ π L
Where,
dvdt = water flow across the membrane of area A in cm2,
L = thickness,
Q = permeability and
Δ π = the osmotic pressure difference between the two
solutions on either side of the membrane.
This equation is strictly for completely perm selective
membrane that is membrane permeable to water but
completely impermeable to osmotic agent.

 The osmotic water flow through a membrane can also be given
by the equation,
dV/dt = (A/ h) Lp (σ Δπ -Δp)
Where, A = membrane area,
h = thickness of membrane,
Lp= mechanical permeability,
σ = reflection coefficient (leakage of the solute),
Δπ = osmotic pressure difference,
Δp = hydrostatic pressure difference.

GENERAL MECHANISM FOR DRUG RELEASE FROM
OSMOTIC PUMPS
 The basic equation which applies to osmotic systems is
dM/dt = dV/dt x c ……………..(eq 1)
Where, dM/dt= mass release,
dV/dt= volumetric pumping rate,
c = concentration of drug.
 But, dV/dt = (A/ h) Lp (σ Δπ -Δp)
Where, A = membrane area,
h = thickness of membrane,
Lp= mechanical permeability,
σ = reflection coefficient,
Δπ = osmotic pressure difference,
Δp = hydrostatic pressure difference.

 As the size of orifice delivery increases, Δp decrease,
so Δπ >> Δp and equation becomes
dV/dt = A/ h Lp (σ Δπ )
 When the osmotic pressure of the formulation is large
compared to the osmotic pressure of the environment,
p can be substituted for Dp.
dV/dt = A/h Lp σπ = A/hk π
(k = Lpσ = membrane permeability)
 Now, equation (1) can be given as
dM/dt = (A/h) k π c = (A / h) k π S
(S = solubility of drug, c taken as S)

Osmotically controlled drug delivery systems:
 Osmotic pressure is used as driving force for these systems to
release the drug in controlled manner.
 Development of osmotic drug delivery systems was pioneered by
Alza and it holds major number of the patents analyzed and also
markets several products based on osmotic principle.
 These systems can be used for both route of administration i.e.
oral and parenteral.
 Oral osmotic systems are known as gastro-intestinal therapeutic
systems (GITS). Parenteral osmotic drug delivery includes
implantable pumps.

BASIC COMPONENT OF OSMOTICALLY
CONTROLLED DRUG DELIVERY SYSTEM
(OSMOTIC PUMPS)
 Drug
 Osmotic agent
 Semi permeable membrane
 Plasticizers

Drugs
 Characteristics of drug candidate for osmotically
controlled drug delivery
 Short biological half-life (2-6h)
 Highly potent drug
 Required for prolonged treatment e.g. Nifedipine,
Glipizide, Verapamil.

Osmotic agents
 Osmogents used for fabrication of osmotic dispensing device
are inorganic or organic in nature, a water soluble drug by
itself can serve the purpose of an osmogent.
 Inorganic water-soluble osmogents
Magnesium sulphate, Sodium chloride, Sodium sulphate,
Potassium chloride, Sodium bicarbonate.
 Organic polymer osmogents
Sodiumcarboxymethylcellulose, Hydroxypropylmethyl
cellulose,Hydroxyethylmethylcellulose, Methylcellulose,
Polyethylene oxide, polyvinyl pyrollidine.

Semi Permeable Membrane
 The semi permeable membrane should be a
stable both to the outer inner environment of the
device.
 The membrane must be sufficiently rigid so as to
retain its dimensional integrity during the
operational lifetime of the device.
 The membrane should also be relatively
impermeable to the contents of dispenser so that
osmogent is not lost by diffusion across the
membrane.
 The membrane must be biocompatible.

Ideal Property of Semi Permeable Membrane:
 The material must possess sufficient wet strength (~105 psi)
and wet modulus (~105 psi) so as to retain its dimensional
integrity during the operational lifetime of the device.
 The membrane exhibit sufficient water permeability so as to
retain water flux rate in the desired range. The water vapor
transmission rates can be used to estimate water flux rates.
 The reflection coefficient (σ) and leakiness of the osmotic
agent should approach the limiting value of unity.
Unfortunately, polymer membranes that are more permeable
to water are also, in general more permeable to the osmotic
agent.
 The membrane should also be biocompatible
 Rigid and non-swelling
 Should be sufficient thick to withstand the pressure within the
device.

Plasticizers
 Different types and amount of plasticizers used in
coating membrane also have a significant importance
in the formulation of osmotic systems.
 They can change visco-elastic behavior of polymers
and these changes may affect the permeability of the
polymeric films.
 Some of the plasticizers used are as below:
Polyethylene glycols
Ethylene glycol monoacetate; and diacetate- for low
permeability
Tri ethyl citrate
Diethyl tartarate or Diacetin- for more permeable
films

ADVANTAGES OF OSMOTICALLY CONTROLLED
DRUG DELIVERY SYSTEMS:
 They typically give a zero order release profile after an initial
lag.
 Deliveries may be delayed or pulsed if desired.
 Drug release is independent of gastric pH and hydrodynamic
condition.
 They are well characterized and understood.
 The release mechanisms are not dependent on drug.
 A high degree of in-vitro and in-vivo correlation (ivivc) is
obtained in osmotic systems.
 The rationale for this approach is that the presence of water
in GIT is relatively constant, at least in terms of the amount
required for activation and controlling osmotically base
technologies.

 Higher release rates are possible with osmotic
systems compared with conventional diffusion-
controlled drug delivery systems.
 The release from osmotic systems is minimally
affected by the presence of food in gastrointestinal
tract.
 The release rate of osmotic systems is highly
predictable and can be programmed by modulating
the release control parameters.

Disadvantages:
 Expensive .
 If the coating process is not well controlled there is a risk
of film defects, which results in dose dumping.
 Size of the hole is critical.
 Dose dumping.
 Retrival therapy is not possible in the case of unexpected
adverse events.

CLASSIFICATION OF OSMOTIC DRUG DELIVERY
SYSTEM:
 Many forms of osmotic pumps are reported in the literature but,
in general they can be divided as
Oral and Implantable systems.
1. Implantable
 The Rose and Nelson Pump
 Higuchi Leeper Pump
 Higuchi Theuwes pump
 Implantable Miniosmotic pump

2. Oral osmotic Pump:
 Single chamber osmotic pump:
-- Elementary osmotic pump
 Multi chamber osmotic pump:
-- Push pull osmotic pump
-- Osmotic pump with non expanding second chamber
 Specific types:
-- Controlled porosity osmotic pump
-- Osmotic bursting osmotic pump
-- Liquid Oral Osmotic System L-OROS
-- Multiparticulate Delayed Delivery Osmotic device
-- Telescopic capsule
-- OROS CT (colon targeting)
-- Sandwiched oral therapeutic system
-- Osmotic pump for insoluble drugs
-- Monolithic osmotic system
-- OSMAT.

1. The Rose Nelson pump:
 In 1955 two Australian physiologist Rose and Nelson
reported the first osmotic pump. They were interested in
delivery of drugs to the gut of sheep and cattle. It consist of,
 A drug chamber with an orifice.
 A salt chamber with elastic diaphragm containing excess
solid salt.
 A water chamber.
 The drug and salt chamber are separated by a rigid
semipermeable membrane.
 The difference in osmotic pressure across the membrane
moves water from the water chamber into salt chamber.

 The volume of the salt chamber increases because of
this water flow, which distends the latex diaphragm
separating salt and drug chamber there by pumping
drug out of this device.
 The pumping rate of Rose-Nelson pump is given by
the equation:
dm/dt = dv/dt *C
Where:
dm/dt = Drug release rate.
dv/dt = Volume flow of water into salt chamber.
C = Concentration of drug into drug chamber.

 Substituting dV/dt = (A/ h) Lp (σ Δπ -Δp) in above
equation gives;
dm/dt = (A/ h) Lp (σ Δπ -Δp) *C
The above equation equation can be used to describe the
behavior of all the devices.
 Osmotic pressure of saturated salt solution is high, small
pressure required to pump the suspension of active agent
is insignificant.
 Thus water permeation across the membrane remains
constant as long as sufficient salt is present, hence a
constant osmotic pressure driving force.

2. Higuchi Leeper pump:
 The design of Higuchi Leeper pump represents the first simplified version
of the Rose Nelson pump made by the Alza Corporation in the early 1970.
 It contains a rigid housing and the semipermeable membrane which is
supported on a perforated frame. Rigid housing is divided in two chambers
by a movable separator.
 The benefit of this pump over Rose Nelson pump is that it does not have
water chamber and the device is activated by water imbibed from the
surrounding environment.

3. Higuchi- Theeuwes pump:
 In the early 1970 Higuchi – Theeuwes developed a similar
form of Rose Nelson pump.
 The semi permeable wall itself act as a rigid outer casing of
the pump .
 The device is loaded with drug prior to use. When the device
is put in an aqueous environment the release of the drug
follows a time course set by the salt used in the salt chamber
and the permeability of the outer membrane casing.

4. Implantable Mini Osmotic Pump:
 Most advanced version developed by Alza Corporation.
 It is composed of three concentric layers- the drug reservoir, the
osmotic sleeve and the rate controlling semipermeable membrane.
 The additional component called the flow moderator is inserted
into the body of the osmotic pump after filling.
 The inner most compartment is drug reservoir which is surrounded
by a osmotic sleeve, a cylinder containing high concentration of
osmotic agent.
 The osmotic sleeve is covered by semipermeable membrane.

 When the system is placed in aqueous environment water
enters the sleeve through semipermeable membrane,
compresses the flexible drug reservoir and displaces the drug
solution through the flow moderator.
 These pumps are available with a variety of delivery rate
between 0.25 to 10 ml per hour and delivery duration between
1 day and 4 weeks.

Oral osmotic drug delivery systems:
 As oral route is the most popular route of administration,
most of the osmotic systems are developed as oral drug
delivery.
 It is possible to deliver APIs at zero-order release rate,
independent of gastric pH and hydrodynamic conditions
with these osmotically controlled drug delivery systems.

1. Elementary Osmotic Pump:
 The elementary osmotic pump is a new delivery system for
drugs. It delivers the agent by an osmotic process at a controlled
rate.
 Control resides in the:
 Water permeation characteristics of a semi permeable membrane
surrounding the formulating agent.
 Osmotic properties of the formulation
1. In its simplest embodiment the system is constructed by coating
an osmotically active agent with the rate controlling
semipermeable membrane.
2. This membrane contains an orifice of critical size through which
agent is delivered.
3. The dosage form after coming into contact with aqueous fluids,
imbibes water at a rate determined by the fluid permeability of
the membrane and osmotic pressure of the core formulation.

 This osmotic imbibitions of water result in formation of a
saturated solution of drug within the core, which is dispensed
at controlled rate from the delivery orifice in the membrane.
 Though 60 -80 percent 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.

Multi Chamber:
1. Push Pull Osmotic Pump:
 Push pull osmotic pump is a modified EOP. through, which it
is possible to deliver both poorly water-soluble and highly
water soluble drugs at a constant rate.
 This system resembles a standard bilayer coated tablet.
 One layer (depict as the upper layer) contains drug in a
formulation of polymeric, osmotic agent and other tablet
excipients. This polymeric osmotic agent has the ability to
form a suspension of drug in-situ when this tablet later
imbibes water.
 The other layer contains osmotic and colouring agents,
polymer and tablet excipients. These layers are formed and
bonded together by tablet compression to form a single
bilayer core.
 The tablet core is then coated with semi permeable
membrane.

 After the coating has been applied, a small hole is drilled
through the membrane by a laser or mechanical drill on the
drug layer side of the tablet.
 When the system is placed in aqueous environment water is
attracted into the tablet by an osmotic agent in both the
layers.
 The osmotic attraction in the drug layer pulls water into the
compartment to form in situ a suspension of drug.
 The osmotic agent in the non-drug layer simultaneously
attract water into that compartment, causing it to expand
volumetrically and the expansion of non drug layer pushes
the drug suspension out of the delivery orifice.

2. 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 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. Example: - the problems that lead to withdrawal of
osmosin,
 The device consists of a normal drug containing porous tablet
from which drug is released as a saturated solution. However
before the drug can escape from the device it must pass
through a second chamber.

 Water is also drawn osmotically into this chamber either
because of osmotic pressure of drug solution or because the
second chamber contain, water soluble diluents such as NaCl.
 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.

Specific Types:
1. 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.

2. Liquid Oral Osmotic System:
 Liquid OROS are designed to deliver drugs as liquid
formulations and combine the benefits of extended release
with high bioavailability.
 They are of three types: -
1. L OROS hard cap
2. L OROS soft cap
3. Delayed liquid bolus delivery system
 Each of these systems includes a liquid drug layer, an osmotic
engine or push layer and a semi permeable membrane coating.
 When the system is in contact with the aqueous environment
water permeates across the rate controlling membrane and
activate the osmotic layer.
 The expansion of the osmotic layer results in the development
of hydrostatic pressure inside the system, thereby forcing the
liquid formulation to be delivered from the delivery orifice.

 Whereas L OROS hardcap or softcap systems are designed
to provide continuous drug delivery, the L OROS delayed
liquid bolus drug delivery system is designed to deliver a
pulse of liquid drug.
 The delayed liquid bolus delivery system comprises three
layers: a placebo delay layer, a liquid drug layer and an
osmotic engine, all surrounded by rate controlling semi
permeable membrane.
 The delivery orifice is drilled on the placebo layer end of
the capsule shaped device.
 When the osmotic engine is expands, the placebo is released
first, delaying release of the drug layer.
 Drug release can be delayed from I to 10 hour, depending
on the permeability of the rate controlling membrane and
thickness of the placebo layer.

3. Delayed Delivery Osmotic Device:
 Because of their semi permeable walls, an osmotic
device inherently show lag time before drug delivery
begins.
 Although this characteristic is usually cited as a
disadvantage, it can be used advantageously.
 The delayed release of certain drug (drugs for early
morning asthma or arthritis) may be beneficial.

4. 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
section.
 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 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 slidable
connected first and second wall sections.
 During the delay period the volume of reservoir containing
the active agent is kept constant, therefore a negligible
pressure gradient exists between the environment of use and
interior of the reservoir.
 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.

5. 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 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.

6. Sandwiched Osmotic Tablets (SOT) :
 It is composed of polymeric push layer sandwiched
between two drug layers with two delivery orifices.
 When placed in the aqueous environment the middle
push layer containing the swelling agents swells and the
drug is released from the two orifices situated on
opposite sides of the tablet and thus SOTS can be
suitable for drugs prone to cause local irritation of the
gastric mucosa.

7. Monolithic Osmotic System:
 It constitutes a simple dispersion of water-soluble agent in
polymer matrix.
 When the system comes in contact with the aqueous
environment.
 Water imbibtion by the active agents takes place rupturing the
polymer matrix capsule surrounding the drug, thus liberating it
to the outside environment.
 Initially this process occurs at the outer environment of the
polymeric matrix, but gradually proceeds towards the interior
of the matrix in a serial fashion.
 However this system fails if more then 20 –30 volume per liter
of the active agents is incorporated in to the device as above
this level, significant contribution from the simple leaching of
the substance take place.

8. Osmat:
 It is a novel osmotically driven matrix system, which utilizes
the hydrophilic polymers to swell, and gel in aqueous
medium forming a semipermiable membrane in-situ.
 Release from such a matrix system containing an osmogen
could, therefore be modulated by the osmotic phenomenon.
 Osmat thus judiciously combines both matrix osmotic
characteristics resulting in a quantum improvement in drug
delivery from swellable matrix system.
 Osmat produces controlled drug release with adequate
delivery rates in an agitation in dependent manner.
 Thus osmat represents simple, versatile, and easy to fabricate
osmotically driven controlled drug delivery system based
upon low cot technology.

9.Controlled Porosity Osmotic Pump:
 The pump can be made with single or multicompartment
dosage form, in either form, the delivery system comprises a
core with the drug surrounded by a membrane which has an
asymmetric structure, i.e. comprises a thin dense skin layer
supported by a porous substructure.
 The membrane is formed by phase inversion process
controlled by the evaporation of a mixed solvent system.
 Membrane is permeable to water but impermeable to solute
and insensitive pore forming additive dispersed throughout
the wall.

 When exposed to water, low levels of water-soluble additive
are leached from polymer materials that were permeable to
water yet remained insoluble.
 Then resulting sponge like structure formed the controlled
porosity walls of interest and was substantially permeable to
both water and dissolved drug agents.
 Rate of drug delivery depends upon the factors are water
permeability of the semi permeable membrane and the
osmotic pressure of the core formulation, thickness and total
surface area of coating.
 All of these variable are under the control of the designer and
do not vary under physiological condition, leading to the
robust performance

 The rate of flow dv/dt of water into the device can
be represented as
dv / dt = Ak / h (Dp-DR)
Where k = Membrane permeability,
A = Area of the membrane,
Dp = Osmotic pressure difference,
DR = Hydrostatic pressure difference.

Advantages of controlled porosity osmotic pumps:
 The device can be so designed that delivery of its drug would
follow zero order kinetics and thus better control over the
drug’s in-vivo performance is possible.
 The drug release from the osmotically controlled drug delivery
systems are independent of the gastric pH and hydrodynamic
conditions, which is mainly attributed to the unique properties
of the SPM employed in the coating of osmotic formulations.
 The delivery rate of drug from these systems is highly
predictable and can be programmed by modulating the terms
 Better release rates than those obtain with conventional
diffusion based drug delivery systems.
 Drug release from the OCODDSs exhibits significant in vitro-
in vivo correlation [ivivc] within specific limits.

Disadvantages of controlled porosity osmotic
pumps:
 Drug release from the osmotic system is affected
to some extent by the presence of food.
 Retrieval of therapy is not possible in the case of
unexpected adverse events.

Factors affecting Drug Release Rate from Osmotic Systems:
1. Solubility: APIs for osmotic delivery should have water solubility
in the desired range to get optimize drug release. Candidate drug for
osmotic delivery should have solubility within the range of 50- 300
mg/ml.
However, by modulating the solubility of these drugs within the
core, effective release patterns may be obtained.
Solubility-modifying approaches:
Use of swellable polymers: vinyl acetate copolymer, polyethylene
oxide.
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®
Use of effervescent mixtures: Mixture of citric acid and sodium
bicarbonate.
Use of cyclodextrin derivatives:
Use of alternative salt form:

 Use of encapsulated excipients: mini-tablet coated with rate
controlling membrane.
 Resin Modulation approach: Ion-exchange resin : Poly (4-
vinyl pyridine), Pentaerythritol, citric and adipic acids.
 Use of crystal habit modifiers: Different crystal form of the
drug may have different solubility, so the excipient which may
change crystal habit of the drug can be used to modulate
solubility.
 Co-compression of drug with excipients: Different excipients
can be used to modulate the solubility of APIs with different
mechanisms like saturation solubility, pH dependent solubility.
Examples of such excipients are organic acids, buffering
agent, etc.

2. Osmotic pressure:
 The next release-controlling factor that must be optimized is the
osmotic pressure gradient between inside the compartment and
the external environment.
 The osmotic pressure can also be found out by the Van’t Hoff
equation:-
π = CRT
Where:π = Osmotic pressure of the solution.
C = Molar concentration of the solute in the solution.
R = Gas constant.
T = Absolute temperature.
 The simplest and most predictable way to achieve a constant
osmotic pressure is to maintain a saturated solution of osmotic
agent in the compartment.
 The following table shows osmotic pressure of commonly used
solutes in CR formulations

3. Type of membrane and characteristics:
 Drug release from an osmotic system is largely independent of
the pH and agitation intensity of GIT tract.
 This is because of its selective water permeable membrane and
effective isolation of dissolution process of drug core from the
gut environment.
 The in–vivo release rate of the system is therefore independent
of its position in the GIT, because the membrane in the
osmotic system is semi permeable in nature any polymer that
is permeable to water but impermeable to solute (drug, organic
and inorganic ions) can be selected example include cellulose
ester such as cellulose acetate, cellulose diacetate, cellulose
triacetate, cellulose propionate, and cellulose ether such as
ethyl cellulose and Eudragit.

 The permeability of this membrane can be increased
further by adding plasticizer to the polymer, which
increases the water diffusion coefficient or hydrophilic
flux enhancer which increases the water sorption of the
membrane.
 A few example of hydrophilic flux enhancer are
Polyethylene glycols 300, 400, 600, 1500, 4000, and
6000(Ramakrishna, 2001)

4. Membrane thickness: -
 A principle factor controlling the rate of penetration of
water into the dispenser is the thickness of the membrane.
 The 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.

5. Size of delivery orifice:
 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 build up in
the system.
 The typical orifice size in osmotic pumps ranges from 600μ
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 tablets. Normally, CO2 laser beam
(with output wavelength of 10.6μ) is used for drilling purpose,
which offers excellent reliability characteristics at low costs.
Indentation that is not covered during the coating process:
Indentation is made in core tablets by using modified punches
having needle on upper punch. This indentation is not covered
during coating process which acts as a path for drug release in
osmotic system.
Use of leachable substances in the semipermeable coating:
e.g. controlled porosity osmotic pump.

EVALUATION:
 In vitro release rate using Dissolution test
 In vivo release rate: determining plasma drug
concentration

67
Q.
No.
QUESTIONS MARKS YEAR
1 Give the principles of
Osmotic drug delivery Systems
5 2012
2 With the help of neat diagram discuss design
and advantages of push pull type of osmotic
delivery system.
Draw a neat labeled diagram showing
working of push pull osmotically controlled
system.
5
3
2011
2011-P
3 Write a note on Oral osmotic pump 4 2012-P
4 What do you understand by osmotic pump 5 2012

Osmotic systems

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