2. CONTENTS
• INTRODUCTION
• PRINCIPLE OF OSMOSIS
• COMPONENTS OF OSMOTIC SYSTEMS
• OSMOTIC DRUG DELIVERY DEVICES
• ADVANTAGES
• DRAWBACKS
• MARKETED PRODUCTS
• EVALUATION
3. INTRODUCTION
• Osmotic systems utilize the principle of
osmotic pressure.
• Reliable controlled drug delivery system.
• Optimization of drug dose and dosing interval.
• Maintaining drug concentration within the
therapeutic window.
• Ensuring efficacy and minimizing toxic effects.
• Better patient compliance.
4. PRINCIPLE OF OSMOSIS
• Osmosis :- The process of movement of
solvent from lower concentration of solute
towards higher concentration of solute across
a semipermeable membrane.
• Osmotic pressure :- The pressure which, if
applied to the more concentrated solution,
would prevent transport of water across the
semipermeable membrane.
5. • Osmotic pressure - Driving force for these
systems to release the drug in controlled
manner.
• Calculation of osmotic pressure :-
∏ = C.R.T
where, ∏ = osmotic pressure
C = concentration of solute
R = gas constant (1.987 cal/mol.deg)
T = absolute temperature
6. • Expression by using vapour pressure
measurements :-
∏ = R T ln (Po/P) / v
Where, ∏ = osmotic pressure
Po = vapour pressure of pure solvent
P = vapour pressure of the solution
v = molar volume of the solution
7. Rate of water flow by osmotic pressure
dV/dt = A.θ.Δ∏/l
Where,
dV/dt = water flow across the membrane
A = area of the membrane
θ = permeability of the membrane
Δ∏ = osmotic pressure difference between two
solutions on either side of membrane
l = thickness of the membrane
8. GENERAL CONSIDERATIONS
• Drug – may act as osmogen & shows good
aqueous solubility
• Osmogenic salt and other sugars
• Semipermeable membrane
• Pore forming agents
• Surfactants
• Wicking agents
• Hydrophilic and hydrophobic polymers
9. COMPONENTS OF OSMOTIC
SYSTEMS
Drug –
Short biological half life
Used for prolonged treatment
e.g. Diltiazem
Carbamazepine
Metoprolol
Nifedipine
Glipizide
10. Semipermeable membrane –
Sufficient wet strength and water permeability
Should be biocompatible
Rigid and non-swelling
Should be sufficient thick to withstand the
pressure within the device.
Permeable to water
Impermeable to solute
13. Drug matrix core
Mixture of both types of polymers is used.
Swellable polymers –
Moderately water soluble drug
Increase hydrostatic pressures
e.g. sodium carboxymethyl cellulose.
Non – swellable polymers –
highly water soluble drugs.
14. Wicking agents –
Draw water into the porous network of a
delivery device by physisorption.
Loosely adhere the solvent at the surface.
Create channels or a network of increased
surface area
Suitable materials – Colloidal SiO2*, Kaolin,
Alumina, TiO2, Niacinamide, SLS*, Bentonite,
Low molecular weight PVP*
15. Solubilizing agents –
Agents inhibiting crystal formation of the drug
e.g. PVP*, PEG 8000, α,β,ϒ- cyclodextrins
Micelle forming surfactant (anionic
surfactants)
e.g. Tween 20,60 & 80, Poly oxyethylene, Poly
ethylene, SLS*
Citrate esters and their combinations with
anionic surfactants
e.g. Triethyl citrate
17. Surfactants –
Regulate the surface energy of wall material
Maintain the integrity of wall
Improve their blending into the composite
e.g. Sorbitan trioleate,
Polyoxyethylene sorbitol bees wax,
Ethylene glycol fatty acid ester,
Triethanolamine oleate,
Polyoxyethylene monostearate,
Potassium oleate
18. Pore forming agents –
Poorly water soluble drugs
Form in situ microporous membrane by
leaching during the operation of the system
Pore formation by volatilization of
components
Pore formation by a chemical reaction in
polymer solution which evolves gas prior to
or during the application
Non toxic
19. • Form channels when removed
• Solid or liquid
• Sodium chloride
• Potassium sulphate
• Potassium phosphate
• Calcium nitrate
• Sucrose
• Mannitol
• Polyvinyl pyrrolidone
20. Flux regulators –
• Added to wall forming materials
• Assists in regulating the fluid permeabilityof
flux through wall
• Increase the flexibility and porosity
Polypropylene
Poly alkylene glycols
Polybutylene
Poly amylene
22. Multi Chamber Osmotic Pump –
Push Pull Osmotic Pump
Osmotic Pump with Non expanding second
chamber
3. SPECIFIC TYPES –
Controlled porosity osmotic pump
Osmotic bursting osmotic pump
Delayed Delivery Osmotic device
Telescopic capsule
Oros-ct (colon targeting)
23. OSMAT
Sandwiched oral therapeutic system
Osmotic pump for insoluble drugs
Monolithic osmotic systems
Liquid oral osmotic system –
• L OROS hard cap
• L OROS soft cap
• Delayed liquid bolus delivery system
24. ROSE NELSON PUMP
• Composed of three chambers –
Drug chamber
Salt chamber
Water chamber
• Semipermeable membrane
• Osmotic pressure difference
• Movement of water from water chamber
towards salt chamber
25. • Kinetics of pumping –
dM/dt = (dV/dt). C
where, dM/dt = Drug release rate
dV/dt = Volume of water flow into salt chamber
C = Concentration of drug in drug chamber
or dM/dt = A.θ.Δ∏.C/l
• Disadvantage –
Beginning of osmotic action when water come
in contact with semipermeable membrane.
26. HIGUCHI LEEPER OSMOTIC PUMP
• Rigid impermeable housing
• Semipermeable membrane
• Salt chamber
• Layer of low melting waxy solid to separate
drug and osmotic chamber
• No water chamber
• Imbibition of water from surroundings
27. HIGUCHI THEEUWES OSMOTIC PUMP
• Rigid housing
• Semipermeable membrane
• Membrane should be strong enough to
withstand the pumping pressure
• Drug is loaded in the device only prior to its
application
• Storage of device for longer duration
• Drug release is governed by salt and
permeability of outer membrane
28. ELEMENTARY OSMOTIC PUMP
• Tablet coated with semipermeable membrane
• Orifice drilled through membrane coating
• In aqueous medium water is drawn through
the semipermeable membrane
• Saturated aqueous solution of drug is formed
• Increase in volume raises the hydrostatic
pressure inside the tablet
• Saturated solution of active agent flow outside
the device through the orifice
29. • Initial release rate :-
dMt/dt = (dV/dt).Cs
Cs = solubilty of the agent inside the tablet
dM/dt = A.θ.Δ∏.Cs/l
Where, dM/dt = release rate of drug
A = area of the membrane
θ = permeability of the membrane
Δ∏ = osmotic pressure difference between two solutions on
either side of membrane
Cs = solubilty of the agent inside the tablet
l = thickness of the membrane
30. MODIFICATIONS IN E.O.P.
• Use of bio-erodible coating
• Addition of carbonate or bicaronate salt to the
drug chamber
• Buffer compounds can be incorporated
• Multilayer composite coating
Thick microporous film
Thin semipermeable membrane
31. PUSH PULL OSMOTIC PUMP
• Modification of elementary osmotic pump
• Deliver both poorly water-soluble and highly
water soluble drugs at a constant rate
• Standard bilayer coated tablet
• Upper layer - drug in a formulation of polymeric,
osmotic agent and other tablet excipients
• Other layer contains osmotic and colouring
agents, polymer and tablet excipients
• These layer are formed and bonded together by
tablet compression to form a single bilayer core
32. • Tablet core is then coated with semipermeable
membrane
• A small hole is drilled through the membrane
by a laser or mechanical drill on the drug layer
side of the tablet
• In aqueous environment water is attracted into
the tablet by an osmotic agent in both the
layers
• in situ suspension of drug is formed
• Expansion of non drug layer pushes the drug
suspension out of the delivery orifice
33. OSMOTIC PUMP WITH NON
EXPANDING SECOND CHAMBER
• The first chamber contains a biologically inert
osmotic agent
• The second chamber contains the drug
• Water is drawn into both the chamber
• The solution of osmotic agent formed in the
first chamber then passes through the
connecting hole to the drug chamber
• It mixes with the drug solution before exiting
through the micro porous membrane
34. OSMOTIC BRUSTING OSMOTIC PUMP
• Similar to an EOP expect delivery orifice is absent
and size may be smaller
• Water is imbibed and hydraulic pressure is built
up inside until the wall rupture
• The content are released to the environment
• Varying the thickness as well as the area the
semipermeable membrane can control release of
drug
• Useful to provide pulsated release
35. TELESCOPIC CAPSULE FOR DELAYED
RELEASE
• It consists of two chambers
• The first contains the drug and an exit port
• The second contains an osmotic engine
• A layer of wax like material separates the two
section
• As fluid is imbibed, the osmotic engine expand
and exerts pressure on the slidable connected
first and second wall sections
36. MONOLITHIC OSMOTIC SYSTEM
• It constitutes a simple dispersion of water-
soluble agent in polymer matrix
• In aqueous environment, water imbibtion
ruptures the polymer matrix capsule
surrounding the drug
• Liberation of drug to the outside environment
• This process occurs at the outer environment of
the polymeric matrix, but gradually proceeds
towards the interior of the matrix in a serial
fashion
38. Osmotic pressure gradient
– Maintainance of saturated solution
of osmotic agent
Size of delivery orifice
– smaller than a maximum size to
minimize drug delivery by diffusion
through the orifice
– larger than a minimum size to
minimize hydrostatic pressure build
up in the system
39. ADVANTAGES
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.
Well characterized and understood.
Release mechanisms are not dependent on
drug.
High degree of in-vitro and in vivo correlation
40. Easy to formulate
Simple in operation
Better patient compliance
Consist and prolonged therapeutic effect
Easy production scale up
The rationale for this approach is that the
presence of water in g.i.t. is relatively
constant, at least in terms of the amount
required for activation and controlling
osmotically base technologies.
41. DRAWBACKS
Toxicity due to dose dumping
Rapid development of tolerance
Hypersensivity reaction may occur
Additional patient education and counseling
is required
Hole size is critical
Costly
43. • Push-pull osmotic systems
• Implantable osmotic systems
Brand Name API
Ditropan XL ® Oxybutynin chloride
Procardia XL® Nifedipine
Glucotrol ® Glipizide
Covera HS ® Verapamil HCl
DynaCirc CR® Isradipine
Invega® Paliperidone
Brand Name API
Viadur® Leuprolide acetate
Chronogesic™ Sufentanil
44. EVALUATION
IN VITRO EVALUATION –
o USP paddle and basket type apparatus
o Dissolution medium –
• Water
• Simulated gastric fluid
IN VIVO EVALUATION –
• Dogs
• Monkeys
45. REFERENCES
• Vyas S.P., Khar R. K., Controlled Drug Delivery
Concepts and Advances, 1st edition, Vallabh
Prakashan, 2010, Delhi, p. 477-501.
• Available at www.pharmainfo.net
