Osmotic Drug Delivery System-very imp NDDS

1. OSMOTIC DRUG DELIVERY SYSTEM
By
Dr. Shreeraj Shah
HOD and Associate Professor
Dept. of Pharmaceutical Technology
L.J. Institute of Pharmacy,
Ahmedabad

2. LIST OF CONTENTS
INTRODUCTION
 ADVANTAGES OF OSMOTIC DRUG DELIVERY SYSTEM
 DISADVANTAGES OF OSMOTIC DRUG DELIVERY SYSTEM
 PRINCIPLE OF OSMOSIS
 BASIC COMPONENTS OF OSMOTIC PUMP
 FACTORS AFFECTING RELEASE OF MEDICAMENT FROM OSMOTIC
DDS
OSMOTIC PUMPS
 FIRST OSMOTIC PUMP (THREE CHAMBER ROSE-NELSON OSMOTIC
PUMP)
 ELEMENTARY OSMOTIC PUMP (EOP)
 CONTROLLED PORSITY OSMOTIC PUMPS (CPOP)
 OSMOTIC BURSTING OSMOTIC PUMP (OBOP)
 PUSH PULL OSMOTIC PUMP (PPOP)
 SANDWICHED OSMOTIC TABLETS (SOTS)
 OROS-CT
 L-OROS
 IMPLANTABLE OSMOTIC PUMPS
 ALZET®
 DUROS®

3.  PULSATILE DRUG DELIVERY OSMOTIC PUMPS
 DELAYED DELIVERY OSMOTIC DEVICES
EVALATION OF OSMOTIC TABLETS
IN VITRO EVALUATION
MARKET PRODUCTS
REFERENCES

4. INTRODUCTION
Osmotic drug delivery uses the osmotic
pressure of drug or other solutes
(osmogens or osmagents) for controlled
delivery of drugs. Osmotic drug delivery
has come a long way since Australian
physiologists Rose and Nelson developed
an implantable pump in 1955.

5. ADVANTAGES OF OSMOTIC DRUG
DELIVERY SYSTEM
The delivery rate of zero-order (which is most
desirable) is achievable with osmotic systems.
Delivery may be delayed or pulsed, if desired.
For oral osmotic systems, drug release is
independent of gastric pH and hydrodynamic
conditions which is mainly attributed to the
unique properties of semipermeable membrane
(SPM) employed in coating of osmotic
formulations.

6. ADVANTAGES
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 vivo–in vitro correlation (IVIVC) is
obtained in osmotic systems because the factors that are
responsible for causing differences in release profile in vitro
and in vivo (e.g., agitation, variable pH) affect these systems
to a much lesser extent.

7. ADVANTAGES
The release from osmotic systems is minimally affected by
the presence of food in the gastrointestinal tract (GIT). This
advantage is attributed to design of osmotic systems.
Environmental contents do not gain access to the drug until
the drug has been delivered out of the device.
Production scale up is easy.

8.  Expensive
 Chance of toxicity due to dose dumping
 Rapid development of tolerance
 Hypersensitivity reaction may occur
 Integrity and consistency are difficult
 Release of drug depends on :
- size of hole/aperture
- surface area
- thickness and composition of membrane
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DISADVANTAGES OF OSMOTIC
DRUG DELIVERY SYSTEM

9. PRINCIPLE OF OSMOSIS
 Osmosis refers to the process of movement of solvent from lower concentration of solute
towards higher concentration of solute across a semi permeable membrane.
 Abbe Nollet first reported osmotic effect in 1748, but Pfeffer in 1877 had been the pioneer of
quantitative measurement of osmotic effect.
 Pfeffer measured the effect by utilizing a membrane which is selectively permeable to water
but impermeable to sugar. The membrane separated sugar solution from pure water. Pfeffer
observed a flow of water into the sugar solution that was halted when a pressure p was
applied to the sugar solution. Pfeffer postulated that this pressure, the osmotic pressure π of
the sugar solution is proportional to the solution concentration and absolute temperature.
 Van’t Hoff established the analogy between the Pfeffer results and the ideal gas laws by the
expression
π = n2RT----------------------(1)
 Where n2 represents the molar concentration of sugar (or other solute) in the solution, R
depicts the gas constant, and T the absolute temperatue.
 This equation holds true for perfect semipermeable membranes and low solute
concentrations.

10.  Another method of obtaining a good approximation of
osmotic pressure is by utilizing vapour pressure
measurements and by using expression:
π = RT ln (Po/P)/v -------- (2)
 Where Po represents the vapour pressure of the pure
solvent, P is the vapour pressure of the solution and v is
the molar volume of the solvent. As vapour pressure can
be measured with less effort than osmotic pressure this
expression is frequently used.

11.  Osmotic pressure for soluble solutes is extremely high. This
high osmotic pressure is responsible for high water flow across
semipermeable membrane.
 The rate of water flow dictated by osmotic pressure can be
given by following equation,
dV/dt = A θ Δπ/l ----------------------- (3)
 Where dV/dt represents the water flow across the membrane
area A and thickness l with permeability θ.
 Δπ depicts the difference in osmotic pressure between the
two solutions on either side of the membrane.
NOTE- This equation is strictly applicable for perfect
semipermeable membrane, which is completely impermeable to
solutes.

12. Schematic representation of the basic model of
osmotic pressure powered drug delivery systems
Vs Vd
PUMP
HOUSING
DELIVERY
ORIFICE
MOVABLE
PARTITION
SEMIPERMEABLE
MEMBRANE
Vs is volume of osmotic agent compartment
Vd is volume of drug compartment

13.  When a single osmotic driving agent is used, the pumping rate of the osmotic device of
(volume per unit time) is defined by
Q/t = Pw Sm [γm (πs- πe)-(ΔPd+ΔPc)] ------------ (4)
 Pw is permeability of semi permeable membrane to water;
 Sm is effective surface area of the membrane;
 γm is osmotic reflection coefficient of the membrane;
 πs and πe are the osmotic pressure of saturated solution of osmotic driving agent and of
the environment where device is located, respectively;
 ΔPd is elevation of internal pressure generated in the drug formulation compartment as
the result of water influx into osmotic agent compartment;
 ΔPc is pressure required to deform drug formulation compartment inward.
 If the net osmotic pressure gradient [γm (πs- πe)] is constant and the hydrostatic
pressure (ΔPd+ΔPc) is negligibly small, equation (4) can be simplified to:
Q/t = Pw Sm (πs- πe) -------------- (5)

14. And a zero order rate of drug release from osmotic
device can be achieved if following conditions are met:
 The amount of osmotic driving agent used is sufficient to maintain a
saturated solution in the osmotic agent compartment i.e. πs is
constant.
 The environmental osmotic activity is either constant or negligibly
small i.e. (πs- πe) ≈ constant.
 The osmotic reflection coefficient is constant and very close to unity
i.e. γm≈1. That means ideal semi permeable membrane, selectively
permeable to water but not to osmotic drug agent, should be used.
 A sufficiently large delivery orifice and a highly deformable
partition should be used. So, ΔPd =ΔPc≈0.

15. BASIC COMPONENTS OF OSMOTIC
PUMP
DRUG
Drug itself may act as an osmogen and
shows good aqueous solubility (e.g.,
potassium chloride pumps).
But if the drug does not possess an
osmogenic property, osmogenic salt and
other sugars can be incorporated in the
formulation.

16. OSMOGEN / OSMAGENT / OSMOTIC
DRIVING AGENT
 For the selection of osmogen, the two most
critical properties to be considered are osmotic
activity and aqueous solubility.
 Osmotic agents are classified as,
 Inorganic water soluble osmogens: Magnesium sulphate,
Sodium chloride, Sodium sulpahte, Potassium chloride,
Sodium bicarbonate etc.
 Organic polymeric osmogens: Na CMC, HPMC, HEMC,
etc.
 Organic water soluble osmogens: Sorbitol, Mannitol,etc.

18. SEMIPERMEABLE MEMBRANE
 Semipermeable membrane must possess certain performance criteria:
 It must have sufficient wet strength and water permeability.
 It should be selectively permeable to water and biocompatible.
 Cellulose acetate is a commonly employed semipermeable membrane for
the preparation of osmotic pumps.
 Some other polymers such as agar acetate, amylose triacetate, betaglucan
acetate, poly (vinyl methyl) ether copolymers, poly (orthoesters), poly
acetals, poly (glycolic acid) and poly (lactic acid) derivatives.
 The unique feature of semipermeable membrane utilized for an osmotic
pump is that it permits only the passage of water into the unit, thereby
effectively isolating the dissolution process from the gut environment.

19. HYDROPHILIC AND HYDROBHOBIC
POLYMERS
 These polymers are used in the formulation development of osmotic
systems containing matrix core.
 The selection of polymer is based on the solubility of drug as well as
the amount and rate of drug to be released from the pump.
 The highly water soluble compounds can be co-entrapped in
hydrophobic matrices and moderately water soluble compounds can
be co-entrapped in hydrophilic matrices to obtain more controlled
release.
 Examples of hydrophilic polymers are Hydroxy ethyl cellulose,
carboxy methyl cellulose, hydroxyl propyl methyl cellulose, etc.
 Examples of hydrophobic polymers are ethyl cellulose, wax
materials, etc.

20. WICKING AGENTS
 It is defined as a material with the ability to draw water
into the porous network of a delivery device.
 The function of the wicking agent is to draw water to
surfaces inside the core of the tablet, thereby creating
channels or a network of increased surface area.
 Examples: colloidon silicon dioxide, kaolin, titanium
dioxide, alumina, niacinamide,sodium lauryl sulphate
(SLS), low molecular weight polyvinyl pyrrolidone (PVP),
bentonite, magnesium aluminium silicate, polyester and
polyethylene,etc.

21. SOLUBILIZING AGENTS
Non swellable solubilizing agents are classified into three
groups:
Agents that inhibits crystal formation of the drugs or otherwise
act by complexation of drug (e.g., PVP, PEG, and
cyclodextrins)
A high HLB micelle forming surfactant, particularly anionic
surfactants (e.g., Tween 20, 60, 80, poly oxy ethylene or
polyethylene containing surfactants and other long chain
anionic surfactants such as SLS).
Citrate esters and their combinations with anionic surfactants
(e.g., alkyl esters particularly triethyl citrate)

22. SURFACTANTS
 They are added to wall forming agents.
 The surfactants act by regulating the surface energy of
materials to improve their blending in to the composite
and maintain their integrity in the environment of use
during the drug release period.
 Examples: polyoxyethylenated glyceryl recinoleate,
polyoxyethylenated castor oil having ethylene oxide,
glyceryl laurates, etc.

23. 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.
 Examples: methylene chloride, acetone, methanol,
ethanol, isopropyl alcohol, ethyl acetate, cyclohexane,
etc.

24. PLASTICIZERS
 Permeability of membranes can be increased by adding
plasticizer, which increases the water diffusion coefficient.
 Examples: dialkyl pthalates, trioctyl phosphates, alkyl
adipates, triethyl citrate and other citrates, propionates,
glycolates, glycerolates, myristates, benzoates,
sulphonamides and halogenated phenyls.

25. FLUX REGULATORS
 Flux regulating agents or flux enhancing agent or flux
decreasing agent are added to the wall forming material;
it assist in regulating the fluid permeability through
membrane.
 Poly hydric alcohols such as poly alkylene glycols and
low molecular weight glycols such as poly propylene,
poly butylene and poly amylene,etc. can be added as
flux regulators.

26. PORE FORMING AGENTS
 These agents are particularly used in the pumps
developed for poorly water soluble drug and in the
development of controlled porosity or multiparticulate
osmotic pumps.
 The pore formers can be inorganic or organic and solid
or liquid in nature.
For example
 Alkaline metal salts such as sodium chloride, sodium
bromide, potassium chloride, etc.
 Alkaline earth metals such as calcium chloride and
calcium nitrate
 Carbohydrates such as glucose, fructose, mannose,etc.

27. Factors affecting release of medicament
from Osmotic DDS
A. Solubility
B. Osmotic pressure
C. Delivery orifice
D. Membrane type

28. A. solubility
• Solubility of drug is one of the most important factors since kinetic of
osmotic release is directly related to the drug solubility.
• The fraction of a drug release with zero order kinetic is given by
•
Where F (z): fraction release by zero order
S: drug solubility in g / cm 3
P: density of core tablet.
• Drug with density of unity and solubility less than 0.05 g / cm3
would release greater than or equals to 95 % by zero order kinetics
• Drug with density > 0.3 g / cm3 solubility would demonstrate with
higher release rate > 70 % by zero order.
• Both highly soluble and poorly soluble drugs are not good candidates
for osmotic drug delivery
F (z) = 1 – S
P

29. B 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 simplest and most predictable way to achieve a
constant osmotic pressure is to maintain a saturated
solution of osmotic agent in the compartment
 The release rate of a drug from an osmotic system is
directly proportional to the osmotic pressure of the core
formulation
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60

30. C. 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.
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60

31. Methods to create a delivery orifice in the
osmotic tablet coating
 Mechanical drill
 Laser drilling : CO2 laser beam
 Use of modified punches
 Use of pore formers : used in controlled porosity
osmotic pump
Ex. of pore formers: dimethyl sulfone, nicotinamide,
saccharides, amino acids, sorbitol, pentaerythritol,
mannitol, organic aliphatic, and aromatic acids,
including diols and polyols
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60

32. D. Membrane type
 Type and nature of polymer
 polymer that is permeable to water but impermeable to
solute can be selected
 Ex. cellulose esters such as cellulose acetate, cellulose
diacetate, cellulose triacetate, cellulose propionate,
cellulose acetate butyrate
 Membrane thickness
 release rate from osmotic systems is inversely
proportional to membrane thickness
 Type and amount of plasticizer
 Chlorpromazine release from CPOP was found to
increase with decreasing amounts of TEC (triethyl citrate)
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33. Classification of Osmotic Pumps

34. Single
osmotic pump
Elementary
osmotic pump
(EOP)
Controlled
porosity
osmotic pump
(CPOP)
Osmotic
bursting
osmotic pump
Multi-chamber
osmotic pump
Push pull
osmotic pump
(PPOP)
Sandwich
osmotic
tablets (SOTS)
Oral osmotic
capsules
OROS- CT
L- OROS
Pelleted delayed
release
Asymmetric
membrane capsule
Telescopic capsule
for delayed release
Implantable
osmotic system
DUROS
osmotic
pump
ALZET
osmotic
pump
Oral osmotic tablet

35. Type of Implantable Osmotic Pumps

36. FIRST OSMOTIC PUMP (THREE CHAMBER
ROSE-NELSON OSMOTIC PUMP)
Drug Chamber
Elastic Diaphragm
Salt Chamber
Rigid Semi permeable membrane
Water Chamber
Delivery orifice
Water to be loaded prior to use was the drawback of rose nelson osmotic
pump

37. ELEMENTARY OSMOTIC PUMP (EOP)
 Rose Nelson pump was further simplified in the
form of elementary osmotic pump (by
Theeuwes,1975) which made osmotic delivery as a
major method of achieving controlled drug release.

38. ELEMENTARY OSMOTIC PUMP (EOP)
Core containing agent
Delivery Orifice
Semi
permeable
membrane
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. This pump eliminates the separate salt
chamber unlike others. 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 the small orifice.
The process continues at a constant rate till the entire solid drug inside the tablet is eliminated leaving
only solution filled shell. This residual dissolved drug is delivered at a slower rate to attain equilibrium
between external and internal drug solution.

39. LIMITATION OF EOP
 Generally in osmotic pumps the semi permeable membrane should
be 200-300μm thick to withstand pressure with in the device.
 These thick coatings lower the water permeation rate, particularly
for moderate and poorly soluble drugs.
 In general we can predict that these thick coating devices are
suitable for highly water soluble drugs.
 This problem can be overcome by using coating materials with high
water permeabilities. For example, addition of plasticizers and
water soluble additive to the cellulose acetate membranes, which
increased the permeability of membrane up to ten fold.

40. Controlled Porosity Osmotic Pump
(CPOP)
 The delivery orifice is formed by incorporation of a
leachable water-soluble component in the coating
material
 Drug release from the whole surface of device rather than
from a single hole which may reduce stomach irritation
problem

41.  The semi permeable coating membrane contains water-soluble
pore forming agents like NaCl, KCl, and Urea.
 Such formed pores becomes permeable for both water and
solutes.
 The release rate from these types of systems has been reported
to be dependent on :
◦ the coating thickness (20-500 𝜇m)
◦ level of soluble components in the coating solubility of the
drug in the tablet core
◦ osmotic pressure difference across the membrane (8-500 atm)
 but independent of the pH and agitation of the release media
 Ex. Chitosan-based controlled porosity osmotic pump (Citric
Acid as pore forming) for colon-specific delivery system:
screening of formulation variables and in vitro investigation :
microbially triggered colon-targeted osmotic pump (MTCT-
OP)
The gelable property at acid condition and colon-specific
biodegradation of chitosan

42. SPECIFICATIONS FOR CONTROLLED
POROSITY OSMOTIC PUMPS
Materials Specifications
Plasticizers and flux regulating
agents
0 to 50, preferably 0.001 to 50
parts per 100 parts of wall
material
Surfactants 0 to 40, preferably 0.001 to 40
parts per 100 parts of wall
material
Wall Thickness 1 to 1000, preferably 20 to
500μm
Micro porous nature 5 to 95% pores between 10Å to
100μm
Pore forming additives 0.1 to 60%, preferably 0.1 to
50%, by weight, based on the
total weight of pore forming
additive and polymer
pH insensitive pore forming
additive (solid or liquid)
preferably 0.1 to 40% by weight

43. SPECIFICATIONS FOR CORE OF
CONTROLLED POROSITY OSMOTIC
PUMPS
Property Specifications
Core loading (size) 0.05ng to 5g or more (include
dosage forms for humans and
animals)
Osmotic pressure developed by
a solution of core
8 to 500atm typically, with
commonly encountered water
soluble drugs and excipients
Core solubility To get continuous, uniform
release of 90% or greater of
the initially loaded core mass
solubility, S, to the core mass
density, ρ, that is S/ρ, must be
0.1 or lower. Typically this
occurs when 10% of the
initially loaded core mass
saturates a volume of external
fluid equal to the total volume
of the initial core mass

44. Osmotic bursting osmotic pump
 Core: API ± osmogents
 Coat: Semi permeable membrane without delivery orifice
 When placed in aqueous environment, water is imbibed and
hydraulic pressure is built up inside the system, then wall ruptures
and the contents are released.
 It is used for pulsated release.
44

45. Multichamber osmotic pump
Push Pull Osmotic System (PPOP)
 They contain two or three compartment
separated by elastic diaphragm
 Upper compartment contain drug with or without
osmogen (drug compartment nearly 60 – 80 %)
and lower compartment (Push compartment)
contain Osmogen at 20 – 40 %.
 It is a bilayer tablet coated with semi permeable
membrane.
 Example Procardia XL for Nifedipine

47. MECHANISM OF PPOP
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48. Sandwiched Osmotic tablets (SOTS)
 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 delivery orifices.
 Advantage : the drug is released from the two orifices situated on
opposite sides of the tablet
48

50.  A more sophisticated version of this device consists of two rigid
chambers, one contains biologically inert osmotic agent such as sugar
or NaCl, and the second chamber contains the drug. When exposed to
aqueous environment, water is drawn into both chambers across the
semi permeable membrane. The solution of osmotic agent then passes
into the drug chamber through the connecting hole where it mixes with
the drug solution before escaping through the micro porous membrane
that forms part of the wall around the drug chamber. Relatively
insoluble drugs can be delivered using this device.
Osmotic agent
containing chamber
Semi permeable
membrane
orifice
Drug containing chamber
Microporous membrane

51. OROS Capsules
OROS- CT
 It is developed by Alza co-operation.
 It is used as a once or twice a day formulation for targeted delivery of drugs
to the colon
 It consist of an enteric coat, SPM & core.
 Core consist of two compartments
- one compartment consist of drug near to orifice.
-Second compartment consist of osmopolymer
 The OROS-CT can be a single osmotic agent or it can be comprise of as
many as five to six push pull osmotic unit filled in a hard gelatin capsule.

52. Cross-sectional diagram of OROS CT delivery system

53. L-OROS
 Liquid OROS controlled release systems are designed to continuous
deliver drugs as liquid formulations.
 A liquid formulation is used for delivering insoluble drugs and
macromolecules.
 Such molecules require external liquid components to assist in
solubilization, dispersion, protection from enzymatic degradation and
promotion of gastrointestinal absorption.
 It combines the benefits of extended-release with high bioavailability.
 These are of two types -:
- L-OROS Soft cap
- L-OROS Hard cap

54. L-OROS Soft cap
 The liquid drug formulation is present in a soft gelatin
capsule, which is surrounded with the barrier layer, the
osmotic layer, and semi permeable 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 osmotic pressure inside the system
forcing the liquid formulation to break through the
hydrated gelatin capsule shell at the delivery orifice.

55. 55
Cross-sectional diagram of L-OROS (Soft cap) delivery system
before and during operation

56. L-OROS Hard Cap
 Another type of L-OROS system consists of a hard gelatin capsule containing a liquid
drug layer, a barrier layer and a push layer surrounded by a semipermeable membrane.
The L-OROS hardcap system was designed to accommodate more viscous suspensions
with higher drug loading than would be possible using softcap design.
Rate controlling membrane
Push layer
Inner Capsule
Delivery orifice
Inner
Compartment
Barrier layer

57. Implantable osmotic pump
Implantable systems further classified as-:
1. For experimental use
2. For human use
For experimental use -:
ALZET®
 It is a miniature, implantable osmotic pumps for
laboratory animals.
 The pump are used to deliver homogenous
solutions or suspensions continuously at a
controlled rate for extended period.
 It consist of Drug reservoir, osmotic sleeve &
semipermeable membrane.

58. ALZET® osmotic pump
58
 Design: Empty reservoir within the core of the pump is filled with the
drug or hormone solution to be delivered and is surrounded by salt
chamber with impermeable layer between them.
 Mechanism: Water enters into the salt chamber through semipermeable
membrane and causes compression of flexible reservoir and delivery
of drug solution.
 Application: To deliver drugs, hormones, and other test agents
continuously at controlled rates from one day to six weeks.

59. Implantable mini
osmotic pump:
Alzet®

60. ALZET OSMOTIC PUMPADVANTAGES
 Ensure around-the-clock exposure to test agents at
predictable levels.
 Permit continuous administration of short half-life proteins
and peptides.
 Convenient method for chronic dosing of laboratory animals.
 Minimize unwanted experimental variables and ensure
reproducible, consistent results.
 Eliminate the need for nighttime or weekend dosing.
 Reduce handling and stress to laboratory animals.
 Small enough for use in mice or very young rats.
 Allow for targeted delivery of agents to virtually any tissue.
 Cost-effective research tool

61. ALZET® Osmotic Pumps are available in three sizes

62. DUROS® osmotic pump
62
 Design :
◦ Implantable drug-dispensing osmotic pump, shaped as a small rod
with titanium housing.
 Mechanism : Through osmosis, water from the body is slowly drawn
through the semi-permeable membrane into the pump by osmotic
agent residing in the engine compartment, which expands the osmotic
agent and displaces a piston to dispense small amounts of drug
formulation from the drug reservoir through the orifice.
 Application: Systemic or site-specific administration of a drug

63. • Affecting factors
– Compositions of osmotic agent
– Thickness of semipermeable membrane
– Surface area

64. DUROS®
 DUROS® implants are designed to bring the benefit of continuous therapy
for up to one year. The non-biodegradable, osmotically driven system is
intended to enable delivery of small drugs, peptides, proteins, DNA and other
bioactive macromolecules for systemic or tissue-specific therapy.
 Viadur® (leuprolide acetate implant), the first marketed product to incorporate
DUROS®, is indicated for the palliative treatment of advanced prostate
cancer.
ADVANTAGES
 Can deliver highly concentrated and viscous formulations.
 Improved patient compliance
 Titanium protects the drug from enzymatic degradation.
 The system can be engineered to deliver a drug at a desired dosing rate with
high degree of precision.

65. PULSATILE DRUG DELIVERY
 Delivering a drug in one or more pulses is
sometimes beneficial, from the required
pharmacological action point of view.
 Mechanical and drug solubility–
modifying techniques have been
implemented to achieve the pulsed
delivery of drugs with an osmotic system.

66. DELAYED-DELIVERY OSMOTIC
DEVICES
 Because of their semipermeable walls, osmotic
devices inherently show a 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 drugs (e.g., drugs
for early morning asthma or arthritis) may be
beneficial. The following slides describes other
means to further delay drug release.

67. Evaluation of Osmotic tablet
 Pre-compression parameters
 Post compression parameters
 Pore diameter
 Coating thickness
 In Vitro drug release
 Zero order release kinetics
 First order release kinetics
 Effect of Osmotic pressure
 Effect of pH on drug release
 Effect of agitation

68. IN VITRO EVALUATION
 The in vitro release of drugs from oral osmotic systems has been
evaluated by the conventional USP paddle and basket type apparatus.
 The dissolution medium is generally distilled water as well as
simulated gastric fluid (for first 2-4 h) and intestinal fluids (for
subsequent hours) have been used.
 The standard specifications, which are followed for the oral controlled
drug delivery systems are equivalently applicable for oral osmotic
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 In vivo evaluation of oral osmotic systems has been carried out mostly
in dogs. Monkeys can also be used but in most of the studies the dogs
are preferred.

69. Marketed Products

70. Marketed Products

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