ANIRBAN NANDI PHARMACY

1. Presented by
Anirban Nandi
M. Pharm.
(PHARMACEUTICS)
Dr. B.C.ROY COLLEGE OF PHARMACY & AHS.
1

2. LIST OF CONTENT
 INTRODUCTION
 PRINCIPLE OF OSMOSIS
 THEORY OF OSMOTIC PUMP
 BASIC COMPONENT OF OSMOTIC PUMP
 CLASSIFICATION OF OSMOTIC PUMP
 FACTOR AFFECTING RELEASE OF MEDICAMENT FROM
OSMOTIC DRUG DELIVERY SYSTEM
 EVALUTION
 MARKETED PRODUCT
 PATENTS
 ADVANTAGES
 DISADVANTAGES
 CURRENT ISSUES
 CONCLUSION
 REFERENCES
2

3. •Osmotic drug delivery uses the osmotic pressure for controlled
delivery of drugs by using osmogens.
•Osmosis :- The net movement of water across a selectively
permeable membrane driven by a difference in osmotic pressure
across the membrane.
•Osmotic pressure :- The pressure which, if applied to the more
concentrated solution, would prevent transport of water across
the semipermeable membrane.
•Osmotic pressure is a colligative property.
•These systems can be used for both route of administration i.e.
oral and parenterals.
3

4. Utilize a membrane permeable to water but
impermeable to sugar is used to separate
sugar solution from pure water.
A flow of water takes place into sugar
Solution that can be stopped until a
pressure π is applied to sugar solution.
4

5. The osmotic pressure π of sugar solution is directly
proportional to:-
(1) Solution concentration.
(2) Absolute temperature.
π =θcRT
Where,
π = osmotic pressure,θ = osmotic co-efficient,
c = molar concentration, R= gas constant,
T= absolute temperature.
5

6. The basic principle of osmosis is expression by (Van’t Hoff),
π = n₂RT
Where,
n₂= molar concentration of sugar
( or other solute ) in the solution,
R = the gas constant and T = temperature.
6

7. Measurement of osmotic pressure by
utilizing vapor pressure measurements,
π = RT In (P₀ /P )/V
Where,
P₀ = the vapour pressure of the pure solvent,
P = the vapour pressure of the solution,
V = the molar volume of the solvent,
7

8. The general expression for the solute delivery rate (dm dt)
from an osmotic pump can be describe by the following
equation :-
dm dt = (AH) Lp(σ∆π―∆p) .C
Where, A= the membrane area, h= the membrane
thickness, Lр = the mechanical permeability,σ = the
reflection co-efficient,π = the osmotic pressure, p = the
hydrostatic pressure, C = the concentration of
compound in the dispensed fluid.
8

9. (1)Drug :- (a)Have short biological half life.
(b)Highly potent drug.
(c)Required for prolong treatment.
Eg Nifedipine etc.
(2) Semipermeable membrane:- Eg- Celulose acetate.
(3)Hydrophilic & hydrophobic polymers :- Eg-CMC.
(4) Wicking agent:- Eg- SLS.
(5) Solubilizing agent:- Eg-PVP.
(6) Osmogens:- Eg-Nacl.
(7) Surfactants :- Eg- Caster oil.
9

10. (8) Coating solvent :-
Eg- acetone and methanol 80 : 20,
acetone and water 90 : 10.
(9)Plasticizer :- Eg- phthalates etc.
(10) Flux regulator :- Eg- polypropylene etc.
(11) Pore forming agent :- Eg- calcium
nitrate.
10

11. (1) Any polymer that is permeable to water but
impermeable to solute can be used as a coating material in
osmotic devices.
(2) It is used to controlled the amount of water
entering to dosage form.
(3) Cellulose acetate is a commonly employed
semipermeable polymer for the preparation of osmotic
pump.
11

12. (1)These polymers are used in the formulation
development of osmotic systems for making drug
containing matrix core.
(2)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.
(3)The selection is based on the solubility of
the drug as well as the amount and rate of
drug to be released from the pump.
12

13. A wicking agent is defined as a
material with the ability for water in to
the porous network of a delivery
device. A wicking agents is either
swellable or non swellable in nature.
13

14. Non swellable solubilizing agents are classified in to
three group :-
(1)Agent that inhibit crystal formation of the drug or
otherwise act by complexation with the drug.
Eg- PVP
(2) High HLB micelle forming surfactant , particularly
anionic surfactant. Eg- Tween 20.
(3) Citrate esters and their combinations with anionic
surfactants. Eg- alkyl esters like triethyl citrate.
14

15. Osmogens are essential ingredient of
the osmotic formulations. They
maintain the osmotic presser in side
the tablet of core and thus provide the
controlled release.Eg- inorganic salts
and carbohydrates.
15

16. Surfactants are particularly useful
when added to wall forming material.
They produce an integral composite
that is useful for making the wall of the
device operative. Eg- poly
oxyethelynated glyceryl recinoleate,
glyceryl laurate etc.
16

17. Solvent suitable for making polymeric
solution that is used for manufacturing
the wall of the osmotic device include
inert inorganic and organic solvent that
do not adversely harm the core wall
and other materials.
17

18. Plasticizers increase the
workability, flexibility and
permeability of the fluids or the
elastic modules of the wall.
18

19. Flux regulating agents are added to
the wall forming materials. It assists
in regulating the fluid permeability
of flux through wall.
19

20. These pore forming agents cause the
formation of microporous membrane.
These agents are particularly used in the
pumps developed for poorly water soluble
drug and in the development of controlled
porosity or multi particulate osmotic
pumps. These pore forming agents cause
the formation of microporous membrane.
20

21. 21

22. Generally two types are there :-
(1) Implantable osmotic drug delivery system
(a)Rose nelson pump.
(b)Higuchi leeper osmotic pump.
(c)Higuchi theeuwes osmotic pump.
(2)Oral osmotic drug delivery system
(a)Elementary osmotic pump.
(b)Multichamber osmotic pump.
---expandable.
---non expandable.
(c)Modified osmotic pump.
(d)Controlled porosity osmotic pump.
(e)Multiparticulate delayed release system.
(f)Monnolithic osmotic system.
22

23. Rose nelson pump :-
 The first osmotic pump developed in
1955 for the delivery of drugs to the
sheep and cattle gut.
 Composed of three chambers.
 Water to be loaded prior to use was the
drawbacks of rose nelson osmotic
pump.
23

24. Rose nelson pump
Water
Chamber
Rigid Semi permeable
membrane
Elastic
Diaphragm
Delivery
orifice
Drug
Chamber
Salt
Chamber
24

25. Higuchi leeper osmotic pump
 No water chamber.
 The activation of device occurs after
imbibition of the water from the
surrounding environment.
 Employed for veterinary use.
 Either swallowed or implanted in body of
animal for delivery of antibiotic or growth
hormones to animals.
25

26. Higuchi leeper osmotic pump
26

27. Higuchi theeuwes osmotic
pump
 The release of the drug from the device is governed by
the salt used in the salt chamber and the permeability
characteristics of outer membrane.
 Diffusional loss of the drug from the device is
minimized by making the delivery port in shape of a
long thin tube.
 Small osmotic pumps of this from are available under
the trade name Alzet®.
 Delivery of DNA by agarose hydrogel implant facilitate
genetic immunization in cattle by using Alzet osmotic
pumps.
27

28. Higuchi theeuwes osmotic pump
28

29. Elementary osmotic
pump
 Major method of achieving controlled drug release.
 It is fabricated as a tablet coated with semipermeable membrane
usually cellulose acetate.
 A small orifice is drilled through the membrane coating.
 The EOP was developed by Alza under the name OROS for
controlled release oral drug delivery formulations.
 Eliminates separate salt chamber.
 Tablet working as a small pump withdrawing water from external
environment.
 Ex. Swellable elementary osmotic pump , an effective device for
delivery of poorly water soluble drug indomethacin.
29

30. Elementary osmotic
pump
Semi permeable
membrane
Core
Delivery Orifice
30

31. MECHANISM OF EOP
31

32. Multi chamber osmotic
pump
Expandable MCOP.
Expandable for solid osmotic system.
 POPP(Push pull osmotic system).
 They contain two or three compartment separated by
elastic diaphragm.
 Upper compartment contain drug with or without
osmogen(drug compartment nearly 6O-8O%) and
lower compartment (push compartment) contain
osmogens at 20- 40 %.
 Example procasdia XL for Nifedipine.
32

33. MECHANISM OF PPOP
33

34. Expandable for liquid osmotic system
34

35. Expandable for liquid osmotic system
35

36. Non expandable MCOP
36

37. Non expandable MCOP
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
37

38.  Before the drug can exit from the device, it must pass
through a second chamber.
 Water is also drawn Osmotically into this chamber due
to osmotic pressure of the second chamber that bears
water-soluble osmogen.
 Such is useful when saturated solution of drug irritate
GIT.
 Reason behind the withdrawl of Osmosin (sodium
indomethacin) .
38

39. Two separate EOP tablet formed in single tablet
(Also know as sandwiched osmotic tablet system)
39

40. Modified osmotic pump
Particles of osmotic agent are coated with an elastic
semipermeable film. These particles are then mixed with the
insoluble drug and compressed in the form of a tablet.
40

41. 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.
Controlled porosity osmotic pump
41

42. Controlled porosity osmotic
pump
42

43.  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).
 Independent of the pH and agitation of the release
media.
 Ex.Chitosan-based controlled porosity osmotic pump
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.
43

44. Mutiparticulate delayed release
system
 In the multiparticulate delayed-release system, pellets
containing drug with or without osmotic agent are
coated with an SPM-like cellulose acetate.
 On contact with an aqueous environment, water
penetrates into the core and forms a saturated solution
of soluble components.
 The osmotic pressure gradient induces a water influx,
resulting in a rapid expansion of the membrane, leading
to the formation of pores.
 The osmotic ingredient and the drug are released
through these pores according to zero order kinetics. 44

45. Monnolithic osmotic system
 Dispersion of water soluble drug is made in a
polymeric matrix and compressed as tablet.
 Tablet is then coated with semi permeable
membrane or drilled on both side of tablet.
 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.
45

46. (A) Solubility.
(B) Osmotic pressure.
(C) Delivery orifice.
(D) Membrane.
(E)Use of wicking agent.
(F)Type and amount of plasticizer.
46

47. (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.
47

48. 48
•The fraction of a drug release with zero order kinetic is given by :-
F (z) = 1 – S
P
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 / cm 3
would release greater than or equals to 95 % by zero order kinetics.
•Drug with density > 0.3 g / cm 3 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.

49. 49
SOLUBILITY MODIFYING APPROACHES
i. Co-compression of drug with excipients
 The modification in solubility of CPOP of a highly
water-soluble drug, diltiazem hydrochloride.
Co-compression of drugs along with solubility
modulating agents can also be utilized for pulsatile
delivery of drugs.
Ex. Demonstrated by salbutamol, highly water
soluble drug.
ii. Use of encapsulated excipients
 Solubility modifier excipient used in form of mini-
tablet coated with rate controlling membrane.

50. 50
iii. Use of swellable polymers
 for drugs having poor aqueous solubility.
Ex. Carbamazapine, theophylline (US patent no.
4,992,278).
vinylpyrrolidone /vinyl acetate copolymer and
polyethylene oxide were used as swelling agent.
iv. Use of effervescent mixtures
Another approach to deliver poorly water-
soluble drugs form osmotic drug delivery system
Citric acid and sodium bicarbonate were used
as the effervescent couple for the delivery of
acetyl salicylic acid (US Patent no. 4,036,228).

51. 51
v. Use of cyclodextrin derivatives
CPOP of Testosterone : increase in solubility of drug from 0.039
mg/ml to 76.5 mg/ml through complexation with sulfobutyl
ether-b-cyclodextrin sodium salt .
Comparative study of CPOP of Testosterone with (SBE)- β -CD
and HP- β –CD.
vi. Resin modulation approach
Release of a highly water-soluble drug, diltiazem
hydrochloride from a CPOP was modulated effectively using
positively charged anion-exchange resin poly (4-vinyl pyridine).
Pentaerythritol was used as osmotic agent and citric and
adipic acids were added to maintain a low core pH to assure that
both the drug and resin carry a positive charge.

52. 52
vii. Use of alternative salt form
In case of metoprolol, use of fumarate salt
instead of tartarate salt achieves optimum
solubility and provided extended release up to
24 hr.
viii. Use of crystal habit modifiers
A slightly soluble drug, carbamazepine along
with crystal modifying agents (combination of
hydroxymethyl cellulose and hydroxyethyl
cellulose) and other excipients was formulated.
(US patent no. 5,284,662).

53. 53
ix. Use of lyotropic crystals
swell in presence of water.
Ex. phosphatidyl choline
(lecithin),phosphatidylethanolamine,
phosphatidylserine, phosphatidylglycerol.
for osmotic delivery of prazosin lecithin and mixture
of soybean phospholipids was utilized (US patent no.
5,108,756).
x. Use of wicking agents
an approach for poorly water-soluble drugs
Ex. of wicking agent : colloidal silicon dioxide, PVP,
sodium lauryl sulfate.

54. 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 release rate of a drug from an
osmotic system is directly proportional
to the osmotic pressure of the core
formulation. 54

55. 55

56. (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 1mm.
56

57. 57
Mechanical drill .
Laser drilling : CO2 laser beam(with out put
wavelength 10.6μ).
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.

58. Drug is released at a constant rate through the controlled
diameter delivery orifice due to the osmotic pressure developed
inside the osmotic core as water influx occurs through the
semepermeable membrane.
The dia. of the orifice is crucial & its optimum size is determined
by the equation ;-
As =(Lv/t) (8π) (η/p)½
Where,
As=C/s area of orifice,
L=dia. of the orifice,
v/t = Vol. released drug /Unit time,
η =Viscosity,
P = Hydrostatic pressure.
58

59. (1)Type and nature of polymer (polymer
that is permeable to water but
impermeable to solute can be selected).
(2) Membrane thickness (release rate from
osmotic system is inversely proportional
to membrane thickness).
(3) Wet strength.
(4) Water permeability.
59

60. (1)The wicking agent are those agents
which help to increase the contact
surface area of the drug with the
incoming aqueous fluid.
(2) The use of the wicking agent help
to enhance the rate of drug released
from the orifice of the drug.
60

61. The polymer can affect the
permeability of the polymer films
can result in the rate of change of
drug release from the osmotic
tablets.
61

62. (1)Characterization of dosage from.
(2)Effect of osmotic agents.
(3)Swelling properties.
(4)Membrane stability and thickness.
(5)Orifice diameter and drug release.
(6)In-vitro drug release study.
(7)In- vivo evaluation .
62

63. 63
IN VITRO DELIVERY RATE MEASUREMENTS
1.Method used by theeuwes and co workers
Osmotic pumps are placed in loosely woven mesh bags
of nylon or polyethylene, and the bags are attached to a
rod, which in turn is attached to a horizontal transfer
arm connected to a vertically reciprocating shaker. The
arms containing several systems are then positioned
over test tubes/containers containing a known amount
of release media.
The release rate (mg/hr) is determined by dividing the
amount of drug in each container by the time (in
hours) of the test interval.

64. 64
IN VIVO DELIVERY RATE MEASUREMENT
Carrid out mainly in dogs.
Theeuwes et al. studied the in vivo release of
indomethacin from OROS pumps in mongrel dogs.
Gastrointestinal transit of an osmotic tablet was
measured by radiolabeling an intact osmotic tablet
(placebo osmosin tablets) and monitoring the
movement of the unit in the GI tract of young and old
healthy volunteers using gamma scintiography (47).
The units were observed to move through the GI tract
at about the same rate as the released contents,
arriving at the cecum about 7 hr after dosing.

65. 65
2.Conventional USP dissolution apparatus 1 & 2.
3. flow-through apparatus.
4. In vitro release of
phenylpropanolaminehydrochloride (PPA)
from the oral osmotic pump system and a
marketed long-acting product (spansules) was
compared using a calibrated Ghannam-Chien
diffusion system as the dissolution apparatus.

66. BRAND NAME SALT USED
Alpress™LP Prazosin For the
treatment of
hypertension
Efidac 24 Chlorphenirami
ne
Allergy
symptoms and
nasal congestion
66

67. 67
PATENTS
YEAR. US PATENT NO. DRUG.
1981 4,265,874 Indomethacin
formulation.
1981 4,305,927 Acetazolamide
formulation.
1984 4,439,195 Theophylline formulation.
1986 4,610,686 Haloperidol.
1987 4,662,880 Pseudoephedrine and
bromopheniramine.

68. (1)Ease of administration.
(2) Greater effectiveness in the treatment of
chronic conditions.
(3)Greater patient convenience due to
simplified dosing schedule.
(4) Consistent blood level within the
therapeutic window.
(5) Enhance bioavailability.
68

69. (6)Reduced inter patient variability.
(7)Decreased dosing frequency.
(8)Improve patient compliance.
(9) Reduced side effect.
(10) Zero order release.
(11) Production scale up is easy.
69

70. 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 orifice diameter.
- surface area.
- thickness and composition of membrane.
70

71. 71
1. Microporous bilayer osmotic tablet for colon-specific delivery.
(Eur J Pharm Biopharm. 2011 Jan 19)
2. Push-pull osmotic pump for zero order delivery of lithium
carbonate: Development and in vitro characterization.
3. Development and evaluation of push-pull based osmotic
delivery system for pramipexole.
4. A controlled porosity osmotic pump system with
biphasic release of theophylline.
5. Release mechanisms of sparingly water-soluble drug from
controlled porosity-osmotic pump pellets using Sulfobutyl ether-
β-Cyclodextrin as both solubilizing & osmotic agent.
(JPS, VOL-98, NO.-6, JUNE-2009, Page NO.-1992)

72. Osmotic pumps have excellence
control on the drug delivery so
these are mostly used now a day.
72

73. (1)A Review Article on Osmotic Drug Delivery System.
Authors: Gohel M.C , Parikh R.K. , Shah N.Y., from L.M.
College Of Pharmacy, Ahmedabad.
(www.pharmainfo.net).
(2)L.F. Prescott. The need for improved drug delivery in
clinical practice, In: Novel Drug Delivery and Its
Therapeutic application, John Wiley and Sons, West
Susset, U.K., 1-11; 1989.
(3)Martin A. Phyical Pharmacy, 4th Edition, Lippincott Williams
and Wilkins 1994; 116-117.
73

74. (4)Aulton's Pharmaceutics; The Design and Manufacture
of Medicines. 3rd ed. Philadelphia, USA: Churchill
Livingstone Elsevier. pp: 99-102.)
(5) Controlled Drug Delivery by S.P.Vyas & Roop K.Khar
Edition 477-501.
(6) Alzet® Osmotic Mini Pump (1976)Product
brochure,Alza,Palo Alto,CA.
(7)J. Pharm. Res. Vol. 5. No. 2. April 2006. P=34.
(8)Ind. J. Pharm. Sci. May – June 2006, P= 295-300.
(9)J. Pharm. Sci. Vol. 96. No. 5. May 2007. P= 1008.
74

75. THANK YOU.
75