OSMOTIC DRUG DELIVERY SYSTEM (IMPLANT AND ORAL DELIVERY)

1. Presented by:
RITEKSHA PATEL
M.PHARMACY

2. LIST OF CONTENT
1. INTRODUCTION
2. PRINCIPLE OF OSMOSIS
3. BASIC COMPONENT OF OSMOTIC SYSTEM
4. CLASSIFICATION OF OSMOTIC PUMP
5. FACTOR AFFECTING RELEASE OF MEDICAMENT FROM
OSMOTIC DDS
6. EVALUATION
7. MARKETED PRODUCT
8. CURRENT ISSUES
9. ADVANTAGES
10. DISADVANTAGES
2

3. 1. Introduction
1. Osmotic drug delivery uses the osmotic pressure for
controlled delivery of drugs by using osmogens.
2. Osmosis : It refers to the process of movement of solvent
from lower concentration of solute towards higher
concentration of solute across the semipermeable
membrane.
3. Osmotic pressure: The pressure exerted by the flow of
water through a semipermeable membrane separating
two solutions with different concentrations of solute.
4. These systems can be used for both route of
administration i.e. oral and parenterals.
3

4. 2.Principle of osmosis
Abbe Nollet first reported osmotic effect in 1748, but
Pfeffer in 1877 had been the pioneer of quantitative
measurement of osmotic effect. Van’t Hoff
established the analogy between the Pfeffer results
and the ideal gas laws by the expression
π = n2RT
Where n2 represents the molar concentration of sugar
(or other solute) in the solution, R depicts the gas
constant, and T the temperatue.
4

5. 3. Basic component of osmotic DDS
1. Drug : itself may act as osmogen otherwise osmogenic salt
can be added in formulation
2. Semipermeable membrane:
criteria: Sufficient wet strength and water permeability
Should be biocompatible and rigid
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
Ex. Cellulose Acetate, Cellulose Triacetate and Ethyl
Cellulose
5

6. 3. Hydrophilic and hydrophobic polymers :( CMC, HEC, HPMC )
4. Wicking agent : ( SLS, PVP, bentonite )
5. Solubilizing agent :(PVP, CD, PEG )
6. Osmogens:( NACL, KCL)
7. Surfactants : (poly oxyethylenated caster oil)
8. Coating solvent : ( acetone and methanol 80:20,acetone and
water 90:10 )
9. Plasticizer : ( phthalates, benzoates, TEC )
10. Flux regulator : ( poly propylene, poly butylene )
11. Pore forming agent:( Calcium nitrate , potassium sulphate)
6

7. 4. Classification of osmotic DDS
1. Implantable Osmotic Drug Delivery System
2. Oral Osmotic Drug Delivery System
7

8. 1. IMPLANTABLE OSMOTIC DDS
A. ROSE NELSON PUMP
Drug Chamber
Elastic Diaphragm
Salt Chamber
Rigid Semi permeable
membrane
Water Chamber
Delivery orifice
8

9. B. HIGUCHI LEEPER OSMOTIC PUMP
1. It has no water chamber, and the activation of the device
occurs after imbibitions of the water from surrounding
environment.
2. Widely employed for veterinary use. It is either swallowed
or implanted in body of an animal for delivery of
antibiotics or growth hormones to animal.
Porous Membrane Support
MgSO4
Movable Separator
Drug Chamber
Rigid Housing
Satd. Sol. Of
MgSO4 contg.
Solid MgSO4
Semi-permeable
Membrane
9

10. PULSATILE RELEASE OSMOTIC PUMP
1. The system is in the form
of a capsule from which
the drug is delivered by
the capsule’s osmotic
infusion.
2. The delivery orifice opens
intermittently to achieve
a pulsatile delivery effect.
3. As the osmotic infusion
progresses, pressure rises
within the capsule,
causing the wall to
stretch.
4. Elastomers such as
styrene-butadiene
copolymer can be used.
Osmogen Semi permeable
Membrane
Separating Barrier
Elastic Cap
Movable piston
Drug Solution
Tiny orifice opened upon stretches under the
Osmotic pressure
10

11. C. HIGUCHI THEEUWES OSMOTIC PUMP
1. In this device, the rigid housing is consist of a semi permeable
membrane. The drug is loaded in the device only prior to its
application, which extends advantage for storage of the device for
longer duration.
2. Diffusional loss of the drug from the device is minimized by
making the delivery port in shape of a long thin tube.
Wall of flexible
collapsible material
SPM
Coating contg. Solid
Osmotic compound
Delivery port
Osmotic Agent layer
Rigid
Semi permeable
Membrane
Fluid to be pumped
Delivery port
Swollen Osmogen layer
Squeezed
Drug Core
11

12. Principle of Operation
ALZET pumps have 3 concentric
layers:
1. Rate-controlling, semi-permeable
membrane
2. Osmotic layer
3. Impermeable drug reservoir
ALZET pumps work by osmotic
displacement. Water enters the pump
across the outer, semi-permeable
membrane due to the presence of a
high concentration of sodium chloride
in the osmotic chamber. The entry of
water causes the osmotic chamber to
expand, thereby compressing the
flexible reservoir and delivering the
drug solution through the delivery
portal. 12

13. 2. ORAL OSMOTIC DDS
A. Elementary osmotic pump
B. Modified osmotic pump
C. Multichamber osmotic pump
- expandable
- non expandable
D. Controlled porosity osmotic pump
E. Multiparticulate delayed release system
F. Monolithic osmtic system
13

14. A. Elementary osmotic pump
Semi permeable
membrane
Core
Delivery Orifice
1. Major method of achieving controlled drug release.
2. The EOP was developed by Alza undre the name OROS
for controlled release oral drug delivery formulations.
14

15. B.MODIFICATIONS IN ELEMENTARY OSMOTIC PUMP
1. The first layer is made up of thick micro porous film that
provides the strength required to withstand the internal
pressure, while second layer is composed of thin semi
permeable membrane that produces the osmotic flux.
2. The support layer is formed by:
Cellulose acetate coating containing 40 to 60% of pore
forming agent such as sorbitol.
Delivery orifice
Drug chamberInner microporous
membrane
Outer semi permeable
membrane 15

16. DELIVERY OF INSOLUBLE DRUG
1. Coating osmotic agent with elastic semi permeable
film
2. Mixing of above particles with the insoluble drug
3. Resultant mixture is coated with the rigid semi
permeable membrane
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Elastic SPM
Rigid SPM
Insoluble Particles
16

17. C. Multichamber osmotic pump
1. Multiple chamber osmotic pumps can be divided into two
major classes
a) Tablets with a second expandable osmotic chamber
b) Tablets with a non-expanding second chamber
a) Tablets with a second expandable osmotic chamber
Osmotic Drug
Core
SPM
Delivery Orifice Delivery Orifice
Polymer push compartment Expanded push compartment
Before operation During operation
17

18. b) Tablet with non expanding second chamber
Depending on
function of
second chamber
non–expandable
osmotic pump
are divided into,
Drug solution
get diluted in
second chamber
before leaving
device.
Two separate
EOP tablet
formed in
single tablet
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19. OROS TRI-LAYER
19

20. DUROS
20

21. D.CONTROLLED PORSITY OSMOTIC PUMPS
1. They are not having any aperture for release of drugs. The
drug release is achieved by the pores, which are formed in
the semi permeable wall in situ during the operation.
2. The semi permeable coating membrane contains water-
soluble pore forming agents. This membrane after formation
of pores becomes permeable for both water and solutes.
Coating Containing Pore
Forming Agents
Pore Formation and Subsequent
Drug Release
Aqueous
Environment
21

22. E. Multiparticulate delayed release system
1. In the multiparticulate delayed-release system, pellets
containing drug with or without osmotic agent are coated
with an SPM-like cellulose acetate.
2. On contact with an aqueous environment, water
penetrates into the core and forms a saturated solution of
soluble components.
3. The osmotic pressure gradient induces a water influx,
resulting in a rapid expansion of the membrane, leading to
the formation of pores.
4. The osmotic ingredient and the drug are released through
these pores according to zero order kinetics.
22

23. F. Monolithic osmtic system
1. Dispersion of water soluble drug is made in a
polymeric matrix and compressed as tablet.
2. Tablet is then coated with semi permeable membrane.
3. When MOS comes in contact with aqueous
environment, the water penetrates in the core and
forms a saturated solution of component which will
generate osmotic pressure which results in the
rupturing of membrane of polymeric matrix
surrounding the agent. Thus liberating drug to move
outside the environment.
23

24. 5. Factors affecting release of medicament
from Osmotic DDS
A. Solubility
B. Osmotic pressure
C. Delivery orifice
D. Membrane
A. Solubility
1. Solubility of drug is one of the most important factors
since kinetic of osmotic release is directly related to the
drug solubility.
2. Both highly soluble and poorly soluble drugs are not good
candidates for osmotic drug delivery.
24

25. B. Osmotic pressure
1. The next release-controlling factor that must be optimized
is the osmotic pressure gradient between inside the
compartment and the external environment.
2. The release rate of a drug from an osmotic system is
directly proportional to the osmotic pressure of the core
formulation
C. Delivery orifice
1. To achieve an optimal zero order delivery profile,the
orifice must be smaller .
2. The typical orifice size in osmotic pumps ranges from
600µ to 1 mm.
25

26. D. Membrane
1. 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
2. Membrane thickness
 release rate from osmotic systems is inversely proportional
to membrane thickness
3. Wet strength
4. Water permeability
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27. Laser light drilling
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28. 6.EVALUATION
1. IN VITRO EVALUATION
2. IN VIVO EVALUATION
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29. 7.MARKETED PRODUCTS
1. Products Incorporating ALZA's OROS® Technology
A. Cardura® XL (doxazosin mesylate) sold in Germany for
the treatment of hypertension.
B. Covera-HS® (verapamil) a Controlled Release system
for the management of hypertension and angina pectoris.
C. Sudafed® (pseudoephedrine) for 24-hour relief of cold
and other respiratory allergies.
D. Procardia XL® (nifedipine) extended-release tablet for
the treatment of angina and hypertension.
2.Products Incorporating ALZA's DUROS® Implant
Technology
A. Viadur® (leuprolide acetate implant) delivers
leuprolide continuously for 12 months.
29

30. 8. CURRENT ISSUES
1. Microporous bilayer osmotic tablet for colon-specific
delivery .
2. Development and evaluation of push-pull based osmotic
delivery system for pramipexole
 offer significant patient benefits by providing enhanced
efficacy and reduced side effects and may also reduce the
number of daily doses compared to conventional therapies.
3. A controlled porosity osmotic pump system with biphasic
release of theophylline
 The developed system was composed of a tablet-in-tablet
(TNT) core and a controlled porosity coating membrane
 osmotic agent: sodium phosphate, sodium chloride .
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31. 9. Advantages
1. Zero order release
2. High release rate
3. High degree of IVIVC
4. Production scale up is easy
5. Increase efficacy of drug
6. Controlled drug delivery
7. Reduce dosing frequency
31

32. 10. Disadvantages
1. Expensive
2. Chance of toxicity due to dose dumping
3. Release of drug depends on :
- size of drug port
- surface area
- thickness and composition of membrane
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