Osmotic drug delivery system

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1) Introduction
2) Principle of osmosis
3) Basic components of osmotic system
4) Classification of osmotic drug delivery system
5) Factors affecting release of medicament from osmotic DDS
6) Evaluation
7) References

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• 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

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Osmotic pumps are the
controlled drug delivery
system typically consist of a drug core
containing osmogen that is coated with
a semipermeable membrane.

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 Zero order release
 Delivery may be delayed or pulsed
 High release rate
 For oral osmotic system, drug release is independent of gastric
pH, agitation, presence of food, GI motility
 The release rate is predictable
 high degree of IVIVC
 Production scale up is easy

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 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 hall
- surface area
- thickness and composition of membrane

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 The solvent membrane control delivery of agent from the
osmotic system across the semi permeable membrane,
which in turn drive the agent out. Water influx of osmotic
pump can be describe as,
dv = A LP σ (ΔП – ΔP)
dt h

Where dv = water influx

dt
A = membrane area
h = membrane thickness
P = mechanical permeability
ΔП = osmotic pressure
ΔP = hydrostatic pressure difference between inside and outside the
system
σ = describes the lickages of solute through the membrane.

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 The general expression for the solute delivery rate,
dM / dt obtained by pumping through the orifice
of the reservoir is given by,
 dM = dV C
dt dt

Where C is concentration of solute if dispersed fluid

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 Drug : itself may act as osmogen otherwise osmogenic salt can
be added in formulation
 Semipermeable membrane:
criteria:
 Sufficient wet strength and water permeability
 Should be biocompatible, rigid and non swelling
 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 esters like Cellulose Acetate, Cellulose Acetate
Butyrate, Cellulose Triacetate and Ethyl Cellulose And Eudragits

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 Hydrophilic and hydrophobic polymers ( CMC, HEC, HPMC )
 Wicking agent : the material with ability to draw water into
the porous network of a delivery device ( SLS, PVP,
bentonite )
 Solubilizing agent (PVP, CD, PEG )
 Osmogens
 Surfactants : act by regulating the surface energy of
materials to imrove their blending into the composite
 Coating solvent : ( methanol, IPA, acetone, cyclohexane )
 Plasticizer : ( phalates, alkyl adipates, TEC )
 Flux regulator : ( poly propylene, poly butylene )
 Pore forming agent

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4.1 Implantable Osmotic Drug Delivery

System

4.2 Oral Osmotic Drug Delivery System

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A. 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 Salt Drug
Water Chamber Chamber Delivery
Chamber orifice

Rigid Semi permeable Elastic

membrane Diaphragm

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 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
 Pulsatile delivery can be achieved

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 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 form are available under the trade
name Alzet®.
 Delivery of DNA by agarose hydrogel implant facilitate genetic
immunization in cattle by using Alzet osmotic pumps

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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 osmtic system

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• Major method of achieving controlled drug release
• The EOP was developed by Alza undre the name OROS for
controlled release oral drug delivery formulations
Delivery Orifice

Core
Semi permeable
membrane

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 Fabricated as tablet coated with semipermeable membrane
usually cellulose acetate
 Small orifice is drilled through the membrane coating
 Eliminates separate salt chamber
 Tablet working as a small pump withdrawing water from
external environment
 Ex. Swellable elementary osmotic pump (SEOP): An
effective device for delivery of poorly water-soluble drug
indomethacin
- The results showed that concentration of wetting agent in
the core formulation was a very important parameter in
D24h and release pattern of indomethacin from SEOP
system. Increasing the amount of wetting agent to an
optimum level (60 mg) significantly increased D24h and
improved zero order release pattern of indomethacin

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i. Expandable MCOP
 Expandable for solid osmotic system
 PPOP ( 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 60 – 80 %) and lower
compartment (Push compartment) contain Osmogen at 20
– 40 %.
 Example ProcardiaXL for Nifedipine
 In vitro and in vivo evaluation of PPOP controlled release
tablet of vinpocetine using numerical deconvolution
technique. (Chemical Abstract, 63- Pharmaceutical Vol.
164., No. 6., August 2010)

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 A liquid formulation is use 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.
 Thus the L-OROS system was designed for continuous
delivery of liquid drug.


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 Depending on
function of
second chamber
non–expandable
osmotic pump
are divided into,

Drug solution
Two separate
get diluted in
EOP tablet
second chamber
formed in
before leaving
single tablet
device.

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 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)

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 also known as sandwiched osmotic tablet system

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 A more sophisticated version of these devices consists of
two rigid chambers : one chamber contains osmogen and
second chamber contain drug

Osmogen

SPM
Drug
Microporous
membrane

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 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

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 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

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 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

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 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.

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 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.

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 MOS is simple to prepare but the system fails if more then 20 –
30 % volume of active agent is incorporated in device because
above this level significant contribution is from leaching of
substance

 Ketoprofen Monolithic Osmotic Pump Control Release Tablet

made up of PEG 6000, NaCl, CMC-Na and Polyvinyl pyrrolidone
which releases drug at 93.51 % for 24 hrs
(Chemical Abstract, 63- Pharmaceutical Vol.
147., No. 6., August 6. 2007. P=1912.,
215217m)

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A. Solubility
B. Osmotic pressure
C. Delivery orifice
D. Membrane type

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• 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
•

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
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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

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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)

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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.
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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)

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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

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 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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 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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 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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 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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 Pore diameter
 Coating thickness
 Hardness
 Friability
 Weight variation
 In vitro evaluation
 In vivo evaluation

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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

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2. Conventional USP dissolution apparatus 1 and 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

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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

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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)

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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. R.K. Verma, D. M. Krishna and S. Garg. Review article on Formulation aspects in the
development of Osmotically controlled oral drug delivery systems, J. Control. Release,
79, 7-27; 2002.
3. Microporous bilayer osmotic tablet for colon-specific delivery,Chaudhary A, Tiwari N,
Jain V, Singh R. , School of Pharmaceutical Sciences, Shobhit University, Meerut, UP,
India., Eur J Pharm Biopharm. 2011 Jan 19

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