Oral Osmotic

Pump
By: Rana Muhammad Awais Khan
06331613002
 INTRODUCTION

Osmosis refers to the process of movement of solvent from lower concentration of

solute towards higher concentration of solute across a semi permeable membrane
till the equilibrium achieved.

Osmotic pressure is the pressure which, if applied to the more concentrated

solution, would prevent transport of water across the semipermeable membrane.

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.
Where, 0 is the Osmotic coefficient of the solution
c is the molar concentration of sugar in the solution,
R is the gas constant,
T is the absolute temperature.
Osmotic pressure for concentrated solution of soluble solutes commonly
used in controlled release formulation are extremely high ranging from
30 atm for sodium phosphate up to 500 atm for a Lactose-Fructose
mixture, as their osmotic pressure can produce high water flow across
semi permeable membrane.

The osmotic water flow through a membrane is given by the equation

dv/dt= AQ∆ Pi /L

Where dv,dt is water flow across the membrane of area A, thickness L,

and the permeability Q in cm2 , ∆ Pi is the osmotic pressure difference
between the two solutions on either side of the membrane.
CLASSIFICATION OF OSMOTIC PUMPS
Osmotic pump
Implantable:
The Rose and Nelson pump
Higuchi Leeper pump
Higuchi Theuwes pump
Implantable mini osmotic pump

Oral:
Single chamber osmotic pump
Multi chamber osmotic pump
Push pull osmotic pump

Specific types:
Controlled porosity OP
Osmotic burst OP
Liquid OROS
Delayed delivery OS
OROS-CT (colon targeting)
Monolithic osmotic system
BASIC COMPONENTS

Drug
Osmotic agent
Semipermeable membrane
Wicking agent
Pore forming agent
Coating agent
CRITERIA FOR SELECTION OF DRUG

Short biological half-life (2- 6 hrs)

High potency
Required for prolonged treatment
(e.G: lifedipine, glipizide, verapamil and chlorpromazine
hydrochloride).
OSMOTIC AGENTS

These are also known as osmogens or osmogents and are used to

create osmotic pressure inside the system.

When the solubility of drug is low then the drug will show zero order
release but at a slow rate. To enhance the release rate osmotic agent is
added in the formulation.

Osmotic agent creates a very high osmotic pressure gradient inside the
system and increases release rate of drug.

Osmotic pressures for concentrated solution of soluble solutes

commonly used in controlled release formulations are extremely high,
ranging from 30 atm for sodium phosphate up to 500 atm for a Lactose-
Fructose mixture.
Contd...
Some of the commercially used osmotic agents
Sodium chloride, Fructose, Sucrose, potassium chloride, xylitol, sorbitol,
citric acid, Dextrose, mannitol and Lactose.

Some mixture used as a osmotic agent

Dextrose +Fructose
Lactose +Fructose
Sucrose+ Fructose
Lactose +Dextrose
Mannitol +Fructose
Mannitol +Dextrose
Dextrose +Sucrose
Mannitol +Sucrose
SEMIPERMEABLE MEMBRANE

• The membrane must possess certain performance criteria such as:

• 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.
• Some of the polymers that can be used for above purpose include
cellulose esters such as cellulose acetate, cellulose diacetate,
cellulose triacetate, cellulose propionate, cellulose acetate
butyrate, and )1Iulose ethers like ethyl cellulose.
WICKING AGENT

The wicking agents are those agents which help to increase the contact
surface area of the drug with the incoming aqueous fluid.

The use of the wicking agent help to enhance the rate of drug released
from the orifice of the drug.

Examples are colloidal 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.
PORE FORMING AGENTS

The pore-forming agents cause the formation of micro porous membrane.

The micro porous wall may be formed in situ by a pore-former by its
leaching during the operation of the system.

The pore formers can be inorganic or organic and solid or liquid in nature.
Like,

Alkaline metal salts such as odium chloride, sodium bromide, potassium

chloride, etc.

Alkaline earth meta. such as calcium chloride and calcium nitrate

Carbohydrates such as glucose, fructose, lactose, etc.

COATING AGENTS

The primary function of solvent system is to dissolved or dispersed the

polymer and other additive and convey them to substrate surface.

Solvent used to prepare polymeric solution include inert inorganic and

organic solvents that do not adversely harm the core ,wall and other
material .The various types of solvents and their combinations are as
follows: methylene chloride, methanol, isopropyl alcohol,
dichloromethane, ethyl acetate, acetone, carbon tetrachloride,
cyclohexane, butyl alcohol, water etc

The mixture of solvents such as acetone-methanol(80:20), methylene

chloride -methanol (79:21), acetone-ethanol(80:20), methylene chloride-
methanol-water (75:22:3)
EVALUATION PARAMETERS:

PORE DIAMETER
COATING THICKNESS
HARDNESS
FRIABILITY
WEIGHT VARIATION
IN VITRO EVALUATION
IN VIVO EVALUATION
ION EXCHANGE
CONTROLLED DRUG
DELIVERY SYSTEM

By: Kainat Waqar

Roll no:06331613006
 INTRODUCTION

• Ion exchange resins (IER) are insoluble polymers that contain

acidic or basic functional groups and have the ability to
exchange counter-ions within aqueous solutions surrounding
them.
• Due to the versatile utility of ion exchange resins, they are being
used for various drug delivery and therapeutic applications. The
efficacy of ion exchange resins mainly depends upon
their physical properties such as degree of cross-
linking, porosity, acid base strength, stability, purity and
particle size. Modified release of drugs from resinate
(drug-resin complexes) is another potential application
of ion exchange resins. 
 STRUCTURE AND CHEMISTRY OF
ION EXCHANGE RESIN
• IER are simply insoluble polyelectrolyte’s that are insoluble polymers
which contain ionisable groups distributed regularly along the
polymer backbone.
• The most common resins used in formulations are cross-linked
polystyrene and polymethacrylate polymers.
• When IER are mixed with a fluid such as water, ions in the fluid can
exchange with the polyelectrolyte’s counter ions and be physically
removed from the fluid.
TYPES OF ION EXCANGE RESINS
CLASSFICATION OF ION
EXCHANGERS
ROLE OF IER IN CONTROLLED DRUG
DELIVERY SYSTEM
• The use of IER into drug delivery systems have been encouraged because
of their physico-chemical stability, inert nature, uniform size, spherical
shape assisting coating and equilibrium driven reproducible drug release in
ionic environment.
• The physical and chemical properties of the IER will release the drug more
uniformly than that simple matrix formulation. Drug molecules attached to
the resins are released by appropriate charged ions in the gastrointestinal
tract, followed by diffusion of free drug molecules out of the resins
Resin- Drug++ X+Resin-....X++ Drug+
Resin+Drug-+ X Resin+...X- + Drug-
• IER have been used as drug carriers in pharmaceutical dosage forms for
controlled release formulation . The prolonged release of the active drug
is accomplished by providing a semi-permeable coating around discrete,
minute, ion exchange resin particles with which the drug component has
been complexed to form an insoluble drug resin complex.
• The semi-permeable coating creates a diffusion barrier and the
thickness of which can be adjusted to provide the desired level of
retardation of drug availability in the gastrointestinal tract over a period
of time. Several preparations involving strong resinates of sulphuric acid
(cation exchange resins) provided more moderate release than the weak
resinates of carboxylic acid . Hence, resinates of strong cationic drugs
are formulated as sustained release suspension, tablets, capsules and
micro particles
DRUG DELIVERY SYSTEMS USING
ION EXCHANGE RESIN
 DRUG DELIVERY APPLICATIONS
 1. Oral Drug Delivery
Modified Release: E.g.
• Sustained release suspension of diltiazem using strong cation
exchange resins for the preparation of microcapsules by emulsion
solvent evaporation method.
• The sustained release suspensions possessed good stability with low
drug leaching, and their release profiles are unchanged when compared
with the dried microcapsules for 120 days at 30 and 45°C.
2. Nasal Drug Delivery
Ion exchange resins to develop novel nasal formulations of nicotine.
• A novel nasal formulation, in the form of a nicotine- Amberlite resin
complex powder, has been developed that provided an optimal
combined pulsatile and sustained plasma nicotine profile for smoking
cessation.
• Amberlite IRP69 and Amberlite IR120 are similar cationic exchange
materials with the same ion exchange capacity but due to a smaller
particle size range (10-150 micron), Amberlite IRP69 had a better flow
property and a better adsorptive capacity than Amberlite IR120.
• The nicotine plasma profiles demonstrated that an initial rapid peak
plasma level of nicotine followed by a sustained elevated level could be
achieved by adjusting the ratio of free to bound nicotine in the
Amberlite powder formulation 30
3. Transdermal Drug Delivery:
• The model for transdermal delivery using ion exchange fibers as
controlling device was designed, and the main objective of their study
was to assess the rationality of the model.
• The release rates of ketoprofen from the carbopol-based gel vehicles
containing ion exchange fibers to which the ketoprofen had been bound
were determined across 0.22 μm micro porous membrane.
• The fluctuation of the release rate of ketoprofen from the vehicles was
much lower compared with that of simple gels, though the cumulative
amount of ketoprofen delivery was less.
• Additional ions could increase the rate and extent of ketoprofen
delivery
4. Ophthalmic Drug Delivery:
• The complexation of betaxolol hydrochloride, an antiglaucoma agent
with ion exchange resins.
• Drug resin particles are incorporated into the structured vehicle,
containing Carbomer 934P as a polymer, to enhance the physical
stability and ease of resuspendability of the product.
• The 0.25% ophthalmic suspension of the drug showed an increased
bioavailability, and pharmaceutically, is an elegant suspension product,
which settles slowly, providing uniform dosage and increased ocular
comfort.
PH CONTROLLED DRUG
DELIVERY
IQRA REHMAN
 CONTROLLED DRUG DELIVERY
• Controlled drug delivery is one which delivers the drug at a
predetermined rate, for locally or systemically, for a specified
period of time.
• Challenges in Oral Drug Delivery
 PH CONTROLLED DRUG DELIVERY SYSTEM

• This type of DDS permits targeting the delivery of a drug only

in the region with a selected pH range.
• Most drugs are either weak acids or weak bases, their release
from formulation is pH dependent
 FEATURES
This type of system is designed for the
controlled release of acidic or basic drugs in GIT
at a rate independent of the variation in GI-pH
with sufficient buffering agents.
 PREPARATION
(USING BUFFER)
• It is prepared by first blending an acidic (or basic) drug with
one or more buffering agents, e.g. a primary, secondary, or
tertiary salt of citric acid
• Granulating with appropriate excipients to form small
granules,
• Then coating the granules with GI polymer .
 USING POLYMER
• Making a core tablet
• Coating a core tablet with a combination of
1. Intestinal fluid-insoluble polymers. Example- ethyl cellulose
2. Intestinal fluid soluble polymer . Example- methyl
cellulose
INTESTINAL PH ACTIVATED DDS
ADVANTAGE
• More uniform drug effect
• Reducing dose frequency
• Improved efficacy and safety ratio

DISADVANTAGE
• Dose dumping
• Stability problem
Bio/mucoadhesive DDS
SIDRA ALTAF
06331613008
Mucoadhesive drug delivery system

 It interacts with the mucus layer covering the mucosal epithelial surface, & mucin
molecules & increase the residence time of the dosage form at the site of the
absorption.
 It is a part of controlled drug delivery system.
 Bioadhesion
 The state in which two materials, at least one of which is biological in nature, are
maintained together for a prolonged time period by means of interfacial forces
Classification of Mucoadhesive Polymers
Mechanism of Mucoadhesion

Generally divided into two steps

 contact stage
 Wetting and swelling of polymer
 consolidation stage
 Interpenetration between polymer chain and mucosal membrane.
 Formation of chemical bonds between entangled chains.
 Contact stage
 The wetting and swelling step occurs when the polymer spreads
over the surface of the mucosal membrane in order to develop an
intimate contact with the substrate.
 This can be readily achieved by placing a bio adhesive
formulation such as a tablet or paste within the
oral cavity or vagina. 
 Swelling of polymers occur because the components within
the polymers have an affinity for water.
Consolidation stage

 The surface of mucosal membranes are composed of high molecular

weight polymers known as glycoproteins.
 In this step interdiffusion and interpenetration take place
between the chains of mucoadhesive polymers and themucous gel network
creating a great area of contact.
 The strength of these bond depends on the degree of penetration
between the two polymer groups.
 In order to form strong adhesive bonds, one polymer group must be
soluble in the other and both polymer types must be
of similar chemical structure. 
Formation of Chemical bond

 In this step entanglement and formation of weak chemical bonds as well as secondary
bonds between the polymer chains and mucin molecules occur.
 The types of bonding formed between the chains include primary bonds such as
covalent bonds and weaker secondary interactions such as van der Waals Interactions
and hydrogen bonds.
Dossage Form

Most common formulation in MDDS are given as below

 Matrix tablets
 (a)Monolithic
 (b)two layered tablets
 In monolithic
 mixture of drug+swelling bioadhesive polymer
|
 bidirectional release & outer side coated with impermeable hyrophobic substances

 Patches
 Films
 Gels &ointments Matrix tablets
Advantages

 MDDS offer several advantages over other controlled oral controlled release
systems by virtue of prolongation of residence of drug in GIT.
 Targeting & localization of the dosage form at a specific site.
 High drug flux at the absorbing tissue.
 MDDS will serve both the purposes of sustain release & presense of dosage
form at the site of absorption.
 Excellent accessibility.
 Painless administration.
 Low enzymatic activity & avoid of first pass metabolism
Disadvantage

 If MDDS are adhere too tightly because it is undesirable to exert too much
force to remove the formulation after use, otherwise the mucosa could be
injured.
 Some patient suffers unpleasant feeling.
 Unfortunately ,the lack of standardized techniques often leads to unclear
results.
 Costly drug delivery system.
 Medications administered orally do not enter the blood stream immediately
after passage through the buccal mucosa.