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A STUDY REPORT ON ORAL CONTROLLED DRUG DELIVERY SYSTEM
RAFQUAT RANA, Regd No. -12109112012
INTRODUCTION:
Over the past 30 years, as the expense and complications involved in marketing new drug
entities have increased, with concomitant recognition of the therapeutic advantages of controlled
drug delivery. Greater attention is being paid on development of oral controlled release drug
delivery systems. The goal in designing controlled release drug delivery system is to reduce the
frequency of dosing, reducing the dose and providing uniform drug delivery. So, controlled
release dosage form is a dosage form that releases one or more drugs continuously in
predetermined pattern for a fixed period of time. Either systematically or locally to specified
target organ. Controlled release dosage forms provide better control of plasma drug levels, less
dosage frequency, less side effect, increased efficacy and constant delivery. The modified
release oral delivery system classification.
Controlled drug delivery is one which delivers the drug at a
predetermined rate, locally or systemically, for a specified period of time. Continuous oral
delivery of drugs at predictable and reproducible kinetics for predetermined period throughout
the course of GIT. Recently, a new generation of pharmaceutical products, called controlled
release drug delivery systems, such as those developed from the osmotic pressure activated drug
delivery system, have recently received regulatory approval for marketing, and their
pharmaceutical Superiority and clinical benefits over the sustained release and immediate
release pharmaceutical products have been increased.
Controlled release drug administration means not only prolongation of the duration of drug
delivery, similar to the objective in sustained release and prolonged release, but the term also
implies the predictability and reproducibility of drug release kinetics.
The basic rationale of controlled drug delivery system is to optimize the biopharmaceutical,
pharmacokinetics and pharmacodynamics properties of drug in such a way that its utility is
maximized through reduction in the side effects and cure or control of condition in the shortest
possible time by the most suitable route. Controlled release denotes that the System is able to
provide some actual therapeutic control, whether this is of a temporal nature, spatial nature, or
both. Controlled drug delivery occurs when a polymer is combined with a drug or active agent
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such that the release from the bulk material is pre-designed.
ADVANTAGES:
Eliminate over or under dosing
Constant level of drug concentration in blood plasma.
Dose reduction.
Increased patient compliance
Prevention of side effects
Night time dosing can be avoided.
Reduces fluctuation of peak valley concentration.
Better stability of drug.
LIMITATIONS:
Poor patient compliance, increased chances of missing the dose of a drug with
short half-life for which frequent administration is necessary.
The unavoidable fluctuations of drug concentration may lead to under medication
or over medication in narrow therapeutic index drug.
A typical peak valley plasma concentration time profile is obtained which makes
attainment of steady-state condition impossible.
DESIGN OF ORAL CONTROLLED DRUG DELIVERY SYSTEM
BIOPHARMACEUTICAL CONSIDERATION:
Biopharmaceutical consideration Rate limiting step of controlled release Rate limiting
step of conventional release.
1. Release from formulation
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2. Movement within body during its passage to site of action.
BIOPHARMACEUTIC CHARACTERISTICS
Molecular Weight
Aqueous Solubility
Partition Coefficient
Ionization
Route Of Administration
Drug Stability....Etc.
PHARMACOKINETIC CHARACTERISTICS
Absorption Rate
Elimination Half-life
Rate Of Metabolism.....Etc.
PHARMACODYNAMIC CHARACTERISTICS
Therapeutic Range
Therapeutic Index
Plasma Concentration Response Relationship
TABLE-1: Design of oral controlled drug delivery system with characteristics.
DRUG RELEASE PATTERN:

Drug disposition follows first order kinetics Rate limiting step is in the
absorptions rate of drug release rapidly and completely absorbed.
POLYMERS FOR CONTROL RELEASE:
These are some of the first materials selected for delivery systems based on their
intended non-biological physical properties:
Polyurethanes for elasticity
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Polysiloxanes for insulating ability
Polymethyl methacrylate for physical strength and transparency

Polyvinyl alcohol for hydrophilicity and swelling
Polyvinyl pyrrolidone for suspension capabilities
Current Polymers used in Controlled Drug Delivery: These polymers became
usable in controlled delivery due to their inert physical characteristics and being
free of leachable impurities
Poly 2-hydroxy ethyl methacrylate
Poly N-vinyl pyrrolidone
Polyvinyl alcohol
Polyacrylic acid
Polyethylene glycol
Polymethacrylic acid
FACTORS INFLUENCING THE DESIGN OF ORAL CONTROLLED DRUG

DELIVERY SYSTEMS
Physicochemical Factors:
Solubility: Low aqueous solubility drugs have low oral bioavailability [5] .Drugs
having good solubility in stomach are poor choice for controlled/sustained
oral dosage forms .The water solubility limits the loading efficiency of
drug into a variety of carrier systems such as liposome and micro
particles, where highly water-soluble drug tend to leach fast from the
carrier. The pH dependent solubility particularly in the physiological pH
range would be another problem for controlled release formulation
because of the variation in pH throughout the gastrointestinal tract and
variation in the dissolution rate. The biopharmaceutical classification
system allow to estimate contribution of three major factors Solubility,
Dissolution and Intestinal Permeability which affect oral absorption. Class
III (High solubility-Low permeability) and Class IV (Low solubility-Low
permeability) drugs is poor candidate for controlled release dosage form.
Drug Stability: A drug in a solid state undergoes degradation at a much slower rate
[6, 7]
. Drugs that are unstable in
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than a drug in suspension or solution
gastric pH can be developed as slow release dosage form and the drugs
can be delayed till the dosage form reaches the intestine. Drugs that
undergo gut-wall metabolism and show instability in small intestine are
not suitable for oral controlled drug delivery systems. Molecular Size and
Diffusivity
[5, 8, 9, and 10]
Diffusivity defined as the ability of a drug to
diffuse through membrane, is inversely related to molecular size.

Diffusivity depends on size and shape of the cavities of the membrane.
More than 95% of drugs are absorbed by passive diffusion. The upper
limit of drug molecular size for passive diffusion is 600 Dalton. The
examples of the drugs which are difficult to control release rate of
medicament from dosage form are proteins and peptides.
Partition coefficients
[9, 10]
: Partition coefficient id defined as the fraction of drug in
an oil phase to that of an aqueous phase. It governs the permeation of

drug particles through biological membrane. Drugs with high partition
coefficient value easily permeate through biological membrane. The
diffusion of drug molecules across rate controlling membrane or through
the matrix system essentially relies on partition coefficient. Drugs that
have lower partition coefficient are not suitable for oral controlled release
drug delivery system and drugs that have higher partition coefficient are
also not suitable for oral controlled drug delivery system because they will
not partition out of the lipid membrane once it gets in the membrane.
Drug pKa and ionization at physiological pH [5, 11]: Drugs existing largely in ionized
form are poor candidate for oral controlled release drug delivery system
because absorption rate of ionized drug is 3-4 times less than that of
unionized form. The pKa range for acidic drug whose ionization is pH
sensitive is around 3.0-7.5 and for basic drug whose ionization is pH
sensitive is around 7.0-11.0 are ideal for optimum positive absorption.
Biological factors:
Absorption
[1, 4]
: The aim of formulating controlled release product is to place a
control on delivery system.
The desirable quality of oral controlled
delivery system is that it should release complete drug and the release
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drug should be completely absorbed. The fraction of drug absorbed from
the system can be lower than the expected due to degradation of drug,
protein binding, site- specific, dose-dependent absorption, poor water
solubility and small partition coefficient.
Distribution [1,
4, and 11]
: Drugs with high apparent volume of distribution, which
influence the rate of elimination of drug, are poor candidate for oral drug
delivery system.
The apparent volume of distribution is one of the
important parameter of drugs that describes the magnitude of distribution

as well as protein binding within the body. The distribution of drug can be
determined by the volume of distribution at steady state and T/P ratio.
T/P=K12/ (K21-b)
Where, T=Amount of drug in peripheral compartment,
P=Amount of drug in central compartment,
K12=Constant for distribution of drug from central to peripheral
compartment,
K21=Constant for distribution of drug from peripheral to
central
compartment,
b=Slow disposition constant.
Metabolism [4, 12]: Metabolism of a drug is either an inactivation, of an active drug or
conversion of an inactive drug to an active metabolite. There are two
factors related to metabolism of drug which restrict the design of
sustained/controlled drug delivery. For chronic administration, drugs that
are capable of either inducing or inhibiting enzyme synthesis, they are
poor candidates for controlled delivery systems due to difficulty in
maintaining uniform blood levels.
Drugs possessing variations in
bioavailability due to first-pass effect or intestinal metabolism are not

suitable for sustained/controlled drug delivery.
[4, 5]
: The duration of action is dependent on the biological half- life. Drugs
with short half-life (greater than 2 hrs) are most suitable for controlled
drug delivery system. Factors influencing the half-life of a drug are
elimination, metabolism, and distribution.
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Half- life
Therapeutic index [5]: Margin of safety can be described by considering therapeutics

index, which is the ratio of median toxic dose and median effective dose.
Therapeutic index = TD50/ED50.
Drugs with low therapeutics index are unsuitable for drug incorporation in
controlled release formulation. The side effects can be minimized by
controlling the concentration within therapeutic range.
Size of dose [5]: If the dose of a drug in conventional dosage form is high, then it is less
suitable candidate for CRDDS. This is because the size of a unit dose
controlled release oral formulation would become too big to administer
without difficulty.
Absorption window [5, 11]: Certain drugs when administered orally are absorbed only
from a specific part of GI tract. This part is known as absorption
window. These kinds of drugs are not suitable for CRDDS
Plasma concentration response relationship [1, 5, 11, 12]:
Plasma drug concentration is more responsible for pharmacological
response than dose. But the drugs having pharmacological activity
independent of plasma concentration are poor candidate for oral CR drug
delivery system.
Concentration dependency on transfer of drug:
If transfer of drug from one compartment to other follows zero order
kinetic process then such drugs are poor candidate for oral CR delivery
system
[1, 13]
. It should be first order kinetics. The following figure
represents various formulation strategies for oral CR drug delivery
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system.
FIG- 1: Representation of formulation strategy of oral crdds.
PHYSIOLOGICAL CONSIDERATIONS:
The physiological properties and anatomical structures of the gastrointestinal tract are
considered in the designing of oral controlled drug delivery system. The stomach and
intestine are the normal sites of oral delivery; however modern drug delivery systems
are designed to deliver drugs to specific sites of GIT such as colon as well as oral
cavity.
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FIG 2: HUMAN DIGESTIVE SYSTEM
BUCCAL MUCOSA:
Buccal controlled drug delivery systems have been developed since the
environment of the oral cavity provides a potential site for drug delivery. The controlled
delivery systems designed are directly accessible to systemic circulation due to rich
blood supply in oral mucosa . the acid hydrolysis and first pass effect can be avoided.
The release of drug is affected by continuous secretion of saliva. The mucin film exists
in oral mucosa offers an opportunity to develop mucoadhesive system, which retain at
absorption site for prolonged time by mucoadhesive binding. The close contact with
absorption membrane causes more absorption of the drug. The sublingual mucosa can
also be used for drug delivery where the flow of saliva is very less. The pH of the buccal
cavity ranges between 5-7 , and does not cause any problem to the drug.
STOMACH:
Controlled and targeted drug delivery systems to stomach could be achieved via the
prolongation of the gastric residence time. Such retention system are important for drugs
which are degraded in intestine, for drugs which exert a local effect in the stomach, for
drugs which are poorly soluble in intestine. Such systems are also advantageous in
improving gastrointestinal absorption of drug with narrow absorption window as well as
for controlling release of the drugs having site specific absorption limitations. Drugs that
are absorbed slowly from GIT can be given as slow release gastric retention systems, to
improve the absorption and bioavailability. The retention of these system depends on
many factors such as gastric anatomy, physiology mobility, pH, and presence of food. It
is not easy to design a system that can overcome all these difficulties.
Blood Flow: The GI tract is a well perfuse organ, receiving about 30% of the total
cardiac output. Changes in blood flow can only affect the absorption of
compounds with high intestinal permeability and lipid soluble molecules.
Blood flow increases considerably after a meal, reaching its peak after a
heavy meal, dosage form given with large volume of water (200 ml or
more) could facilitate drug absorption by inducing an increase in blood
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flow.
pH and Volume: pH of the gastric environment affects the performance of orally

administered drug. The pH of the stomach in fasted condition is about 1.5
to 2 and in fed condition usuaaly it is 2 to 6. A large volume of water
administered with oral dosage form changes the ph of stomach to the pH
of water initially. This change occurs because the stomach does not have
enough time to produce sufficient quantity of acid before emptying of
liquid from the stomach. It does not improve the dissolution of basic
drug. Basic drugs will have a better chance to dissolve in fed condition
rather than in fasted condition. Gastric volume is important for
dissolution of dosage forms following their administration.
Gastric Mucosa: Mucus is considered to be an absorption barrier in GI tract, since it
acts as a stagnant diffusion layer. Many substances can interact with
mucus and change its physicochemical properties. This interaction can
also result in a change in absorption of these compounds.
Gastric Secretion: On average the daily intake of a normal adult is 3-4 kg of food and
drink. In response to this stimulus the stomach secretes an additional 5L
of fluids. The volume produced within the first hour of eating can be as
much as twice that of meals . a distinct pH gradient exists in the stomach
after a meal; the ingestion of food is the major stimulus to the acid
secretions. This effect is more pronounced if the meal is of high protein
content.
Gastric Emptying: The rate of emptying is controlled by feedback mechanism from
duodenum and ileum. Solids are not emptied in the fed state unless they
have been ground to particle size of 2mm or less. Since grinding and
mixing takes place in antral area, dosage form tends to reside in this area
due to their large size, while multi unit dosage form are dispersed and
emptied with food. In the fed state more fluid is available for dissolution
of dosage form. Total time for gastric emptying varies from 2 - 6 hr.
Gastric Motility: it is difficult to control the environment of dosage form in the GIT at
all the times following ingestion. The existing motility pattern at the time
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of administration affects the performance of oral dosage forms.
SMALL INTESTINE:
Controlled and targeted drug delivery systems specifically to small intestine are
designed to avoid or bypass the acid environment of stomach and release the drug in
alkaline environment of small intestine. These systems are designed for drugs which are
acid labile, irritate the gastric mucosa, adsorbed from small intestine and required for
local effect in the intestine.
Advantages:
Avoidance of first pass metabolism.
Selective treatment of diseases and infections of mesenteric lymphatic.
Enhanced absorption of large molecules such as proteins and peptides.
Inhibition of cancer cell metastasis.
Systemic absorption of drugs which are highly hydrophilic and stable at all pH
values.
Oral administration of antigens.
COLON:
The colonic environment properties such as pH, mucoadhesion, microflora and large
surface area are taken into consideration while designing the colon specific systems. The
longer colonic transit times provide prolonged time for drug release and the colonic
microflora provides various enzymes to trigger release.
CLASSIFICATION:
1. Continuous release system Dissolution Controlled drug release system
a. Matrix Dissolution Controlled system
b. Encapsulation/coating Dissolution Controlled drug
release system
2. Diffusion Controlled drug release system

a. Matrix Diffusion system.
b. Reservoir devices.
3. Dissolution and diffusion Controlled drug release system.
4. Ion exchange resin drug complexes.
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5. pH independent formulation.
6. Osmotic pressure controlled system

7. Hydrodynamic pressure controlled system.
8. Altered density system.
a. Floating tablets
b. Muco-adhesive system
c. Size based system.
1. Dissolution controlled drug release system

a. Matrix type
Also called as Monolithic dissolution controlled system since the drug
homogenously dispersed throughout a rate controlling medium waxes (beeswax,
carnauba wax, hydrogenated castor oil etc.) which control drug dissolution by
controlling the rate of dissolution through
1. Altering porosity of tablet.
2. Decreasing its wettability.
3. Dissolving at slower rate.
Exhibit First order drug release.
Drug release determined by dissolution rate of polymer.
Examples: Demeaned extencaps, Dimetapp extentabs.
SDM
Soluble API mixed

with SDM
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FIG 3: Monolithic dissolution controlled system
b. Encapsulation type
Also called as Coating dissolution controlled
system since the drug encapsulated, with slowly dissolving material like
cellulose, PEG, PMA (polymethylacrylates) & waxes. Dissolution rate of
coat depends upon stability & thickness of coating.
Slow dissolving
Or erodible coat
Soluble drug
FIG 4: Coating dissolution controlled system

2. Diffusion controlled drug release system
It is a major process for absorption in which no energy required. In this drug
molecules diffuse from a region of higher concentration to lower concentration
until equilibrium is attained and it is directly proportional to the concentration
gradient across the membrane. In this system release rate is determined by its
diffusion through a water-insoluble polymer. There are two types of diffusion
devices:
a. Matrix diffusion system
b. Reservoir diffusion system
a. Matrix Diffusion
The matrix system is defined as a well-mixed composite of one or more
drugs with gelling agent i.e. hydrophilic polymers. Matrix systems are
widely used for sustaining the release rate. It is the release
system
which prolongs and controls the release of the drug that is dissolved or
dispersed
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Rigid Matrix Diffusion
Materials used are insoluble plastics such as PVP & fatty acids.
Swell able Matrix Diffusion
Also called as Glassy hydrogels. Popular for sustaining the
release of highly water soluble drugs. Materials used are hydrophilic gums.
Examples: Natural: Guargum, Tragacanth.
Semi-synthetic: HPMC, CMC, Xantham gum.
Synthetic: Polyacrylamide.
Advantages:
Easier to produce than reservoir or encapsulated devices.
Versatile, effective and low cost.
Possible
to
formulate
high
molecular weight compounds.

Increased
the
stability
by protecting
the
drug
from hydrolysis or
other derivative changes in gastrointestinal tract.

Disadvantages:
The ghost matrix must be removed after the drug has been released.
The release rates are affected by various factors such as,
food and the rate transit through the gut.
Cannot provide pure zero order release.
b. Reservoir System:
Also called as laminated matrix device.
Hollow system containing an inner core surrounded in water insoluble

membrane.
Polymer can be applied by coating or micro encapsulation.
Rate controlling mechanism - partitioning into membrane with subsequent

release into surrounding fluid by diffusion.
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Commonly used polymers - HPC, ethyl cellulose & polyvinyl acetate.
DRUG
DRUG reservoir is saturated

(Unit activity).
DRUG
Rate-controlling membrane has

Constant thickness(x), diffusivity (D)
And solubility coefficient for drug.
DRUG
FIG 5: Reservoir Diffusion Drug Delivery System

3. Dissolution & Diffusion Controlled Release system :
In this drug is encased in a partially soluble membrane and pores are created due
to dissolution of parts of membrane. It permits entry of aqueous medium into core
& drug is dissolved or diffused out of the system.
Ex- Ethyl cellulose & PVP mixture dissolves in water & creates pores of
insoluble ethyl cellulose.
Insoluble membrane
Entry of dissolution fluid
Drug Diffusion
Pores created by dissolution of soluble fraction of membrane.
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FIG 6: Dissolution Diffusion Controlled System
4. Ion exchange resins controlled release system
POLYMER
COATING
ETHYL
CELLULOSE
COATING
DRUG
CONTAINING
RESIN GRANULES
DRUG
CONTAINING
RESIN
GRANULES
POLYETHYLENE
GLYCOL
COATING
POLYMER COATING-DRUG RESIN

DESIGN
POLYMER COATED DRUG RESIN

DISPERSION
FIG 7: Ion Exchange Resins

Ion exchange resins are cross-linked water insoluble polymers carrying ionizable
functional groups. These resins are used for taste masking and controlled release
system. The formulations are developed by embedding the drug molecules in the
ion-exchange resin matrix and this core is then coated with a semi permeable
coating material such as Ethyl Cellulose. This system reduced the degradation of
drug in GIT.
The
most
widely
used
and
safe
ion-exchange
resin
is
divinylbenzenesulphonate. In tablet formulations ion-exchange resins have been

used as disintegrant.
5. pH independent formulation:
Most drugs are either weak acids or weak bases. The release from controlled
release formulation is pH dependent. However buffers such as salts of amino acids,
citric acid, phthalic acid phosphoric acid or tartaric acid can be added to
formulation to maintain a constant pH thereby rendering pH independent drug
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release.
A buffered formulation is prepared by mixing a basic or acidic drug with

appropriate pharmaceutical excipient and coating with GI fluid permeable film
forming polymer. When GI fluid permeates through the membrane, the buffering
agents adjust the fluid inside to suitable constant pH thereby rendering a constant
rate of drug release.
6. Osmotically controlled release system:
Osmosis is defined as the movement of solvent from lower to higher concentration
through semi permeable membrane. Osmotic pressure is the hydrostatic pressure
produced by a solution in a space divided by a semi permeable membrane due to
difference in concentration of solutes. This technology provides zero order release
for hydrophilic drugs. Drug may be osmotically active, or combined with an
osmotically active salt (e.g., NaCl). Semi permeable membrane is usually made
from cellulose acetate.
Examples: Glucotrol XL, Procardia XL.
H2 O
Rigid, Water permeable
membrane controls delivery
rate.
Drug
Saturated drug solution exits

Only through hole in
Outer membrane.
Drug
FIG :8 Osmotic Pressure Controlled System
7. Hydrodynamic pressure controlled system

One of the most feasible approaches for achieving a prolonged and predictable
drug delivery profile in the GI tract is to control the gastric residence time i.e.
Gastro retentive Dosage Forms (GRDFs). These are primarily controlled release
drug delivery systems, which gets retained in the stomach for longer periods of
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time, thus helping in absorption of drug for the intended duration of time. Gastric
retentive drug delivery devices can be useful for the spatial and temporal delivery
of many drugs. Thus, control of placement of a DDS in a specific region of the GI
tract offers numerous advantages, especially for drug exhibiting an absorption
window in the GI tract.
The intimate contact of the DDS with the absorbing membrane and also the
potential to maximize drug absorption may influence the rate of drug absorption.
These considerations have led to the development of oral controlled release (CR)
dosage forms possessing gastric retention capabilities. Drug may not be absorbed
uniformly over the length of the gastrointestinal tract, because dosage form may be
rapidly transported from more absorptive upper regions of the intestine to lower
regions where the drug is less absorbed and drug absorption from colon is usually
erratic and inefficient. Moreover, certain drugs are absorbed only from the stomach
or the upper part of small intestine.
FIG 9: Hydrodynamic Controlled System

One such approach is Floating Microspheres (Hollow Microspheres). Floating
Microspheres are gastro retentive drug delivery systems based on non-effervescent
approach. Hollow Microspheres are in strict sense, spherical empty particles
without core. These Microspheres are characteristically free flowing powders
consisting of proteins or synthetic polymers, ideally having a size less than 200
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micrometer.
Gastro-retentive floating Microspheres are low-density systems that have sufficient

buoyancy to float over gastric contents and remain in stomach for prolonged
period. The drug is released slowly at desired rate resulting in increased gastric
retention with reduced fluctuations in plasma drug concentration. Floating
Microspheres to improve patient compliance by decreasing dosing frequency, better
therapeutic effect of short half-life drugs can be achieved. Enhanced absorption of
drugs which solubilize only in stomach, Gastric retention time is increased because
of buoyancy.
Floating Microspheres are prepared by solvent diffusion and evaporation methods
to create the hollow inner core. Floating Microspheres are characterized by their
micrometric properties such as particle size, tapped density, compressibility index,
true density and flow properties including angle of repose, scanning electron
microscopy, in vitro floatability studies, in vivo floatability studies in dogs, in vitro
drug release studies and stability studies etc.
8. Altered density system
Several approaches have been developed to prolong the residence time of drug
delivery system in the GI tract. One such approach is the bio adhesion approach
which is based on the adherence of bio adhesive polymer to mucin/epithelial
surface of GI tract. The other approach is to alter the formulations density by using
either high or low density pellets. It includesa. Floating Tablets :
Floating systems are low-density systems that have sufficient buoyancy to float
over the gastric contents and remain in the stomach for a prolonged period.
While the system floats over the gastric contents, the drug is released slowly at
the desired rate, which results in increased gastro-retention time and reduces
fluctuation in plasma drug concentration.
It can be used for local action in the proximal GIT. Poorly soluble and
unstable as well as poorly absorbable (intestine) drugs are suitable candidate for
floating dosage units.* these system are designed to have lesser gravity than
gastric contents, thereby float on the gastric fluid for extended period.
Hypodermically balanced systems (HBS) are typical examples of floating
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tablets.
b. Muco-adhesive system:
The term bio adhesion describe materials that bind to the biological
substrates, such as mucosal membrane. Adhesion of bio adhesive drug
delivery devices to the mucosal tissue offers the possibility of creating an
intimate and prolonged contact at the site of administration. This prolonged
residence time can result in the enhanced absorption and in combination with
a controlled release of drug also improved patient compliance by reducing the
frequency of administration. The epithelial adhesive properties of mucin have
been applied in the development of gastro retentive drug delivery systems.
FIG 10: Mechanistic Aspect Of Muco-Adhesive System

Buccal and sublingual mucosa offers for mucoadhesion and several
advantages such as lead to rapid onset of action, high blood levels, and
avoidance of first pass effect. Drugs can be applied locally and removed
easily. Synthetic polymers including cellulose derivatives and poly (acrylic
acid) as well as plant gums have been used for the preparation of bioadhesive
systems.
c. Size based system Microspheres are small spherical particles, with diameters in the micrometer
range (typically 1 m to 1000 m (1 mm)). Microspheres are sometimes
referred to as microparticles.
There are two types of microparticles are present, namely:
1. Microspheres
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2. Microcapsules
FIG 11: Microcapsule

Microspheres
Microspheres can be manufactured from various natural and synthetic
materials. Glass Microspheres, polymer Microspheres and ceramic
Microspheres are commercially available. Solid and hollow Microspheres
vary widely in density and, therefore, are used for different applications.
Hollow Microspheres are typically used as additives to lower the density of a
material. Solid Microspheres have numerous applications depending on what
material they are constructed. The Microspheres were characterized by
shape, size, surface morphology, size distribution, incorporation efficiency,
and invitro drug release studies. The outer surfaces of the core and coated
Microspheres, which were spherical in shape, were rough and smooth,
respectively. The size of the core Microspheres ranged from 22 to 55 m,
and the size of the coated Microspheres ranged from 103 to 185 m.
1. Microcapsules
A microcapsule is a system that contains a well defined core and a welldefined envelope: the core can be solid, liquid, or gas; the envelope is made
of a continuous, porous or nonporous, polymeric phase. The drug can be
dispersed inside the microcapsule as solid particulates with regular or
irregular shapes. Other forms may consist of a pure or dissolved solution,
suspension, emulsion, or a combination of suspension and emulsion. Specific
applications sometimes require modifications, e.g., when proteins are
encapsulated they may contain stabilizers as well as the active ingredient.
Also, the core can be something other than a chemical meant for release. An
interesting application is the encapsulation of gases for the use of ultrasonic
G O V E R N M E N T
P H A R M A C Y
I N S T I T U T E ,
P A T N A .
Page
21
imaging [13-15].
TABLE 2: MARKETED DRUG PRODUCTS WITH THEIR MECHANISM BASED

CLASSIFICATION
Sl.
TECHNOLOGY
No.
BRAND NAME
DRUG
MANUFACTURER
1.
Diffusion controlled system
Welbutrin XL
Bupropion
GlaxoSmithKline
2.
Matrix system tablet
Ambien CR
Zolpidem
tartarate
Sanofi-Aventis
3.
Tussionex
Methods using ion Exchange
Pennkinetics
Resin
ER suspension
4.
Methods
Using
Osmotic
Pressure
Elementary
Osmotic pump
Efidac 24@
Push-Pull
Glucotrol XL@
Osmotic system
Hydrocodon
Polistirex and
UCB inc.
Chlorpheneramine
Polistirex
Chlorpheneramine
Novartis
maleate
Glipizide
Pfizer inc.
5.
pH independent formulation
Inderal @ LA
Propanolol HCL
Wyeth Inc.
6.
Altered density formulation
Modapar
Levodopa and
Benserazide
Roche Products,
USA
MECHANISTIC ASPECT OF ORAL CONTROL RELEASE DRUG DELIVERY

SYSTEM FORMULATION
FORMULATION STRATEGY OF ORAL

CONTROL RELEASE DRUG DELIVERY
SYSTEM
Dissolution
Method
Sustained
Sustained
Using
System
System
IonExchange
Methods
using
osmotic
pressure
pH
Altered
Independent
Density
Formulation
Formulation
G O V E R N M E N T
P H A R M A C Y
I N S T I T U T E ,
P A T N A .
Page
22
Diffusion
Dissolution controlled release :

Dissolution is defined as solid substance solubilized in a given solvent. It is a
rate determining step when liquid is diffusing from solid. Several theories
explain dissolution: Diffusion layer theory, Surface renewal theory, Limited
solvation theory.
Noyes Whitney Equation:
dc/dt = k*D*A (Cs C)
dc/dt = D/h A* (Cs C)
Where,
dc/dt = Dissolution rate,
k
= Dissolution rate constant (1st order).
D = Diffusion coefficient/diffusivity.
Cs = Saturation/ maximum drug solubility.
C
= Conc. Of drug in bulk solution.
Cs-C = Conc. Gradient.

h = Thickness of diffusion layer.
Diffusion system :
The Higuchi Equation describing the drug release from this system:
Q = [D/T (2A- Cs*t)] 1/2
Where, Q=amt of drug release per unit surface area at time t,
D=diffusion
coefficient
of
drug
in
the
release
medium,
=porosity of the matrix,

Cs=solubility of drug in release medium,
T=tortuosity of matrix,
A=concentration of drug present in matrix per unit volume.
G O V E R N M E N T
P H A R M A C Y
I N S T I T U T E ,
P A T N A .
Page
23
Rate controlling step: Diffusion of dissolved drug in matrix.
Ion-Exchange resin tablets:

These tablets are commonly developed by embedding the drug molecules in the
ion exchange resin matrix and this core is then coated with a semipermeable
coating membrane called EC.
D
Electrolysis In
Gastric Environment
E
D
ANIONIC RESIN
CATIONIC RESIN
EPOSITIVELY CHARGED
ELECTROLYTE
FIG 12: Mechanism of Ion Drug Release from Ion-Exchange Resins

Osmotically controlled release system:
The volume flow of water into core reservoir dv/dt is expressed as:
dv/dt = K A/ h (-p)
Where,
K= Membrane permeability,
A= effective surface area
h = thickness of semi permeable membrane,
= osmotic pressure difference,
p = hydrostatic pressure difference.
G O V E R N M E N T
P H A R M A C Y
I N S T I T U T E ,
P A T N A .
Page
24
FIG 13: Osmotically Controlled System
APPROACHES TO IMPROVE ORAL BIOAVAILABILITY[5]

Most of the medicinally important compounds such as peptides and proteins are not
effectively absorbed by gastrointestinal barriers. To improve the absorption of the drugs
through GIT tissue barrier, various approaches have been developed. These approaches
include addition of absorption enhancers in formulations, lipid carrier systems, chemical
modification, receptor and carrier mediated targeting and use of particulate systems.
Absorption Enhancers:
Many compounds with different structures have been reported and proposed as effective
absorption promoters for drugs after oral administration. According to their ability of
promotion and their adverse reactions with the mucosal membrane of the GIT, these
absorption promoters are classified into four groups (Muranishi 1990) and they are
summarized in table.
Group I compounds promote drug absorption with strong, fast reactivity, and also with
a rapid recovery of barrier function. Group II compounds exert a moderately fast reactivity at
absorption promotion and also possess fast recovery. Group III compounds are relatively
effective in absorption enhancement of drugs, but show slow recovery rate. Group IV
miscible solvents have been showed moderate reactivity. All groups of compounds are
structurally possessing hydrophilic moieties such as C10-C20 acyl chain or steroid skeleton
and hydrophilic groups such as hydroxyl, carboxy, glyceryl or sulfate groups (Muranishi,
1990).
Prodrugs and Analogues:

By improving the physicochemical properties of the drugs, one can improve the absorption of
the drugs, thereby can improve the bioavailability. The improved physicochemical properties
can be obtained by chemical modification; the drugs are chemically modified into either
prodrugs or analogs (Sinkula and Yalkowsky, 1975). Prodrug possesses a promoiety that does
not express the pharmacological effect. Analogues exert pharmacological activity without
disintegration. Generally absorption through lipid membrane of GI barriers occurs by simple
diffusion. So, the prodrug designing involves improving the lipophilicity to raise the
G O V E R N M E N T
P H A R M A C Y
I N S T I T U T E ,
P A T N A .
Page
25
permeability across the membrane.
Lipidic Systems
Micro and Multiple Emulsions:
Aqueous
Phase
Oil
Phase
w/o/w emulsion
o/w/o emulsion
Figure 14: Multiple Emulsions

Micro and Multiple Emulsions are having the dispersed phase diameter less than 0.1m and
appear translucent or transparent and they are thermodynamically stable compared to the
conventional emulsions. Multiple emulsions are containing three phases either o/w/o or w/o/w
type. The selection of type of emulsions depends on the hydrophilic or lipophilic nature of the
drugs. Recently, to improve absorption and retaining drug in the GIT, the potential of micro
and multiple emulsions have been studied. Lipid soluble drugs are more suitable to these
system for improved absorption (Goff, 1997; Borkovee, 1992).
Mixed Micelles:
G O V E R N M E N T
P H A R M A C Y
I N S T I T U T E ,
P A T N A .
Page
26
FIG 15: Mixed Micelles
Mixed Micelles have also been employed to promote intestinal and rectal absorption of
macromolecules and small molecular weight drugs. Mixed micelles are reportedly safe and
effective absorption enhancers for small particles delivered into large intestine. Mixed
micelles bearing particulate ink and colloidal gold as markers showed enhanced absorption
and the study concluded that the upper limit for particles absorbed by the large intestine under
the influence of mixed micelles was 40nm. The absorbed particulates were selectively
transported into lymphatic and accumulated in regional lymph nodes(Muranishi,1985;
Muranishi et al.,1987).
Liposomes:
FIG 16: Liposomes

Liposomes are vesicles comprising double layer membrane of phospholipid. Liposomes
fundamentally resemble the structure of biomembrane. Liposomes can encapsulate drugs and
are susceptible to endocytosis or fusion with cell membranes. Different types of liposomes
such as unilamellar and multilamellar liposomes can be prepared by various specific methods
of preparations (Szoka and Papahadjopoulos, 1980).
Furthermore, incorporating acidic or basic lipids, the surface charge of the liposomes can
utilize liposomes, as controlled release carrier systems or to stabilize or target drugs.
Particulate System:
In oral administration, particulate systems such as micro and nanoparticles have been utilized
as a carrier for drugs to improve the absorption through GI membrane (Hagan, 1990).
Microparticles or microspheres and nanoparticles are polymeric particles ranging in size from
1-100 m and 1-1000nm, respectively (Kreuter, 1983). Natural as well as synthetic polymeric
G O V E R N M E N T
P H A R M A C Y
I N S T I T U T E ,
P A T N A .
Page
27
materials have been used to develop particulate systems in which drugs are encapsulated
entrapped or dissolved. The studies with particulate systems concluded that microencapsulation of proteins markedly affects the oral uptake as well as post absorption
pharmacokinetic parameters, possibly. Furthermore, it is believed that particulate material
itself would be absorbed from the GIT. The application of particulate system by oral route
includes the delivery of antigens and vaccines.
Carrier or Receptor mediated Conjugated systems:
INTESTINAL
LUMEN
SYSTEMIC
CIRCULATION
Intestinal
Epithelial cell
Drug-Carrier
Interaction
Drug release
from Carrier
Drug-Conjugate
Drug Carrier
Transportation
FIG 17: Carrier Mediated Transportation System

To overcome the problem associated with poor bioavailability of peptides and proteins, a
number of carrier mediated systems are being developed. Various specific carrier mediated
systems may be harnessed for oral drug delivery. The properties of the systems in common
involve epithelial cells (enterocytes), transfer across the cell membrane or the entire cell, and
release from the basal surface of the intestinal epithelial cell into circulation.
Various natural transporter systems such as the intestinal peptide transporter, the bile acid
transport system , immunoglobulin transport (IgG and polymeric IgA), viral and bacterial
transport and other receptor mediated transport [ Iron(Fe) and Vitamin B12 ] have been
G O V E R N M E N T
P H A R M A C Y
I N S T I T U T E ,
P A T N A .
Page
28
exploited for the specific oral delivery of drugs.
The intestinal Peptide transporter

By using the intestinal peptide transporter systems, molecules and dipeptides
including glyceryl sarcosine, glycyl L-proline , amino--lactam antibiotics
(Kimura,1983;Hori,1988), peniciliins (amoxicillin, ampicillin, cyclacillin) (Walter et
al ., 1996; Iseki, 1989),ACE inhibitors (captopril, enalapril, etc.) (Swan et al., 1995),
cephalosporins (cofactor, cefadroxil etc.) (Walteret al ., 1996; Kramer et al 1988)
and rennin inhibitors (Pauletti , 1996) are transported. This transport system a high
capacity but is limited to molecules of a small molecular weight (less than 600 Da)
and to peptides or molecules having structural homologies with di and tri peptides
The Bile Acid Transport System:

The high uptake capacity of the intestine for bile salts(>20 per day), and subsequent
targeting of the bile salts to the liver offer the use the bile acid transport system to
enhance intestinal absorption of small, poorly absorbed molecules and to specifically
target drugs to liver (Kramer et al., 1983 , 1994). Several classes of compounds have
an affinity for bile acid transporter . they include steroid analogs (ouabain and
fusidic acid ), cyclic peptides (antamanide), cyclic stomastatin derivatives (octretide)
and rennin inhibitors (Swan et al., 1996,1997). Liver specific targeting the bile salts
have been shown for conjugated chlorambucil, phalloidin and various oxaprolyl
peptides (Kramer , 1994). However, successful systemic delivery after oral
administration of a bile acid conjugate would require the presence of a
biodegradable linkage or prodrug approach for the drugs to remain in the circulation
rather than to be delivered to liver.
Immunoglobulin transport:
For the transport of IgG, many neonatal animals possess luminal receptors for the
transport of IgG. These receptors specifically bind to other immunoglobulin located
in intestine and showing specific binding characteristics at different pH(bind at pH
6.0 and do not bind at pH 7.4). this point endows the system for binding to intestinal
IgG (pH<6.5) and release in serosal plasma (pH7.4) (Rodewald,1980). In the IgG
G O V E R N M E N T
P H A R M A C Y
I N S T I T U T E ,
P A T N A .
Page
29
transport system, molecules such as ferritin has been linked to the IgG molecules to
follow the uptake and transcytosis. Thus , it would be possible for large molecules
such as ferritin to be carried into neonate following conjugation with IgG.
Across many types of epithelial cells, operates the receptor mediated transport of
polymeric IgA and IgM mediated by the polymeric immunoglobulin receptor
(pIgR). Transport occurs through binding of Immunoglobulin Fc to the pIgR on the
basal surface of the epithelial cells followed by transport of the molecules from the
basolateral to apical surface. In the same way, drugs (or peptides) bound to IgA or
IgM may be transported (Mostov et al., 1984; Hirt,1993).
Lectin, Adhesions, Haemagglutinins and Toxins Mediated Transport:

The surface characteristics of the bacteria and viruses are responsible for the specific
binding to the intestinal epithelium and thereby subsequent internalization within the
intestinal epithelial cells. Many plant and some animal Lectin and toxins possess the
same property. The binding of these molecules have been shown the potential to be
utilized for the intestinal transit of drugs. The conjugated molecules have shown
specific uptake and transcytosis of the drugs across the intestinal epithelial cell.
Receptor Mediated Endocytosis of Transferrin and Uptake of Fe.

The iron uptake through intestine is mediated by lactotranferrin. Iron bound to
transferring is internalized by intestinal epithelial cells. The transferring receptors
are located in the brush-bordered membrane (Mazurier et al., 1985; Johnson et al.,
1983). Inside the cell, the lower pH of endosomal vesicles (pH 5.5) causes
dissociation of iron from the transferrin and releases iron to the cell (Dautry-Varset
et al., 1983; Klausner tranferrin could be targeted. Antibodies to the transferrin
receptor could be equivocally used to target the drug by employing the receptor
mediated uptake system.
Vitamin B12 Mediated Transport Systems:

In VB12 uptake system, the absorption occurs by receptor mediated transport, which
G O V E R N M E N T
P H A R M A C Y
I N S T I T U T E ,
P A T N A .
Page
30
is facilitated by intrinsic factor (IF). The molecular level uptake of VB12 is
schematically given in Fig. . VB12 possess many advantages as a carrier for oral drug
delivery;
Molecular weight is small (1356 Da) and less immunogenic.
Relatively inexpensive and can be modified easily to provide suitable functional

groups for conjugation with proteins and peptides.
The extended period for uptake of VB12 generally lasts for 6-8h, hence, serves as a
natural sustained delivery system that is highly suitable for oral peptide/ protein
delivery.
VB12+ IF (Intestine)
Binds to an IF receptor located on
The epithelium of small intestine
(Predominantly ileum)
VB12 IF complex
Internalization through sub epithelial

Vacuole (presumably an endosome)
IF in complex degraded by
Cathepsin and VB12 released.
Released VB12 binds to

Intracellular transcobalamin II
Transcytosis of VB12-transcobalamin II
Complex into circulation
31
FIG18: Molecular level natural uptake of Vitamin B12
G O V E R N M E N T
P H A R M A C Y
I N S T I T U T E ,
P A T N A .
Page
Vitamin B12 uptake and Nanoparticles:

Formulating the drugs loaded nanoparticles to which VB12 is linked could result in a
1000-10000 fold increase in the absorption. This process documented to protect the
drugs from the enzymes and other degradative processes , during intestinal transit.
Moreover, when the drugs incorporated into nanoparticles , the chemical linkage of
VB12 and drug can be avoided. For effective delivery, such nanoparticulate systems
would need to be designed so that they remain intact within the intestine however
functionally release their contents, when they reach the circulation (Russel-Jones,
G O V E R N M E N T
P H A R M A C Y
I N S T I T U T E ,
P A T N A .
Page
32
1996b; Desai et al., 1996).
CONCLUSION:
In last three decades a number of modern technologies including targeting
concepts have emerged for successful and oral controlled delivery of various bioactives. The limitations have been overwhelmed by these modern technologies, which
are providing effective local as well as systemic drug levels at desirable sites with
improved safety profiles. The matrix , ionexchange, floating and bio-adhesive
concepts have been developed and explored for controlled and pulsatile oral delivery.
Current research involves the sophistication of designing oral controlled/sustained
drug delivery systems with modern targeting or site-specific concepts. The
development in the bio engineering and cell biology provided newer dimensions to
designing and fabrication of oral systems. The gastric retention time has been
prolonged by using the buoyancy and bio-adhesive principles; furthermore site
specific bioadhesion concept has been introduced to enhance the efficacy of these
systems. The vesicular and lipidic systems extend more advantages for lymphatic and
mucosal uptake. The carrier and receptor mediated uptake of novel systems provided
an insight into their functioning for the site-specific oral delivery. By these systems,
the pre-systemic clearance of drugs can be avoided and drug can reach pre-selected
site in intact form. The development in the in vitro and in vivo evaluation methods
with the aid of modern scientific technologies provides necessary tools to make the in
vitro dissolution test, which stimulates in vivo condition more precise and decisive.
From the above discussion, I conclude that the controlled release
drug delivery system is very helpful in increasing the efficiency of the dose as well as
the patient compliance. Moreover, the reasonable cost of oral controlled release drug
delivery system has lead ease of market penetration as replacement of oral
G O V E R N M E N T
P H A R M A C Y
I N S T I T U T E ,
P A T N A .
Page
33
conventional drug delivery system.
REFERENCE:
1.
Brahmankar DM, Jaiswal SB. Biopharmaceutics and Pharmacokinetics:

Pharmacokinetics. 2nd ed. Vallabh Prakashan, Delhi: 2009; 399-401.
2.
John C, Morten C, The Science of Dosage Form Design, and Aulton: Modified
release peroral dosage forms. 2nd ed. Churchill Livingstone. 2002; 290-300.
3.
Lee VHL. Controlled Drug Delivery Fundamentals and Applications: Influence of

drug properties on design. 2nd ed. Marcel Dekker, Inc. New York: 1987; 16-25.
4.
Modi Kushal, Modi Monali, Mishra Durgavati, Panchal Mittal, Sorathiya Umesh,
Shelat Pragna. Oral controlled release drug delivery system: An overview. Int. Res.
J. Pharm. 2013; 4(3):70-76.
5. Vyas SP, Khar RK. Controlled drug delivery: Concepts and Advances. 1st ed.
Vallabh prakashan; 2002; 156-189.
6.
Y.W. Chien. Novel drug delivery system. Volume 50.
7.
Allen LV, Popvich GN, Ansel HC. Ansels Pharmaceutical dosage form and drug
delivery system. 8th ed. 2004; 260-263.
8.
Patrick JS. Martins Physical Pharmacy and Pharmaceutical Sciences. 3rd ed.
Varghese Publishing House. Bombay: 1991; 512-519.
9.
Kar RK, Mohapatra S, Barik BB. Design and characterization of controlled release
matrix tablets of Zidovudin. Asian J Pharm Cli Res. 2009; 2:54-6
10. Lachaman L, Liberman HA, Kanig JL.The theory and practice of industrial
pharmacy. 3rd ed. Bombay: Varghese publishing house 1987.
11. Jain NK. Controlled and novel drug delivery. CBS publisher and distribution. 1997;
1-25.
12. Venkataraman DSN, Chester A, Kliener L. An overview of controlled release
system. Handbook of pharmaceutical controlled release technology. Marcel Dekker
Inc. 2000; 1-30.
13. Mamidala R, Ramana V, Lingam M, Gannu R, Rao MY. Review article factors
influencing the design and performance of oral sustained/controlled release dosage
form. Int. journal of pharmaceutical science and nanotechnology. 2009; 2:583.
14. Gupta S, Singh RP, Sharma R, Kalyanwat R, Lokwani P. Osmotic pumps: A review.
Int. journal of comprehensive pharmacy. 2011; 6:1-8.
15. Robinson JR, Lee VH. Controlled drug delivery. 2nd ed. Marcel Dekker, 1987; 415.
G O V E R N M E N T
P H A R M A C Y
I N S T I T U T E ,
P A T N A .
Page
34
16. Kamboj S, Gupta GD. Matrix Tablets: An important tool for oral controlled release
dosage form. Pharmainfo. Net. 2009; 7:1-9.
17. Bechgaard H, Nielson GH. Controlled release multiple units and single unit dosage.
Drug Dev.and Ind. Pharm. 1978; 4:53-67. dx.doi.org/10.3109/03639047809055639
18. Wise DL. Handbook of pharmaceutical controlled release technology. Marcel
Dekker Inc. New York: 2002; 432-460.
19. Tripathi KD. Essentials of Medical pharmacology. 5th ed. New Delhi: Jaypee
Brothers Medical Publishers (P) Ltd; 2003.
20. Gibaldi M. Biopharmaceutics and clinical pharmacokinetics. 3rd ed. Philadelphia:
Lea & Febiger; 1984.
21. Heilmann K. Therapeutics systems rate controlled drug delivery: Concept and
Development. 2nd ed. Stuttgart Georg Thieme Verlag; 1984.
22. Conaghey OM, Corish J, Corrigan OI. Iontophoretically assisted in vitro membrane
transport of nicotine from a hydrogel containing ion exchange resin. Int.J. Pharm.
1998; 170-225. dx.doi.org/10.1016/s0378-5173 (98)00144-6
23. Mahore JG, Wadher J, Umekar MJ, Bhoyar PK. Ion exchange resins: Pharmaceutical
application and recent advancement. Int. J. Pharm.Sci. Rev. Res. 2010; 1(2): 8-13.
24. Javed Ali, RK Khar, Alka Ahuja. Dosage form design. 4th ed. Birla Publication Pvt.
Ltd; 2009; 181-194.
25. Cristina M, Aranzazu Z, Jose ML. Review: Critical factors in the release of drugs
from sustained release hydrophilic matrices. Int. journal of Research in Ayurveda
and Pharmacy. 2011; 21: 1701-08.
26. Herbig SM, Cardial JR, Korsmeyer RW, Smith KL. Asymmetric membrane tablet
coating for osmotic drug delivery. J. Control. Release. 1995; 35:127-136.
dx.doi.org/10.1016/0168-3659 (95)00028-7
27. Gupta RN, Gupta R, Basniwal PK, Rathore GS. Osmotically controlled oral drug
delivery systems; A Review. Int. J. Pharm. Sci. 2009: 1(2): 75-269.
28. Wagnaer JG. Biopharmaceutics and pharmacokinetics. Org. Intelligence Publisher;
1971: 57-148.
29. Srikanth MV,Sunil SA, Rao NS, Uhumwangho MU, Ramana Murthy KV. Ion
exchange resins as controlled drug delivery carriers. J. Sci. Res. 2010; 2(3): 11-597.
G O V E R N M E N T
P H A R M A C Y
I N S T I T U T E ,
P A T N A .
Page
35
30. Ballard BE. Sustained and controlled release drug delivery system. USA: Marcel
Dekker Inc. 1978; 76- 106.

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A STUDY REPORT ON ORAL CONTROLLED DRUG DELIVERY SYSTEM

RAFQUAT RANA, Regd No. -12109112012

such that the release from the bulk material is pre-designed.

A STUDY REPORT ON ORAL CONTROLLED DRUG DELIVERY SYSTEM

RAFQUAT RANA, Regd No. -12109112012

DESIGN OF ORAL CONTROLLED DRUG DELIVERY SYSTEM

2. Movement within body during its passage to site of action.

A STUDY REPORT ON ORAL CONTROLLED DRUG DELIVERY SYSTEM

RAFQUAT RANA, Regd No. -12109112012

TABLE-1: Design of oral controlled drug delivery system with characteristics.

DRUG RELEASE PATTERN:

Polysiloxanes for insulating ability

A STUDY REPORT ON ORAL CONTROLLED DRUG DELIVERY SYSTEM

RAFQUAT RANA, Regd No. -12109112012

Polymethyl methacrylate for physical strength and transparency

FACTORS INFLUENCING THE DESIGN OF ORAL CONTROLLED DRUG

. Drugs that are unstable in

than a drug in suspension or solution

A STUDY REPORT ON ORAL CONTROLLED DRUG DELIVERY SYSTEM

RAFQUAT RANA, Regd No. -12109112012

[5, 8, 9, and 10]

Diffusivity defined as the ability of a drug to

diffuse through membrane, is inversely related to molecular size.

: Partition coefficient id defined as the fraction of drug in

an oil phase to that of an aqueous phase. It governs the permeation of

: The aim of formulating controlled release product is to place a

control on delivery system.

The desirable quality of oral controlled

drug should be completely absorbed. The fraction of drug absorbed from

A STUDY REPORT ON ORAL CONTROLLED DRUG DELIVERY SYSTEM

RAFQUAT RANA, Regd No. -12109112012

: Drugs with high apparent volume of distribution, which

The apparent volume of distribution is one of the

important parameter of drugs that describes the magnitude of distribution

Drugs possessing variations in

bioavailability due to first-pass effect or intestinal metabolism are not

: The duration of action is dependent on the biological half- life. Drugs

elimination, metabolism, and distribution.

A STUDY REPORT ON ORAL CONTROLLED DRUG DELIVERY SYSTEM

RAFQUAT RANA, Regd No. -12109112012

Therapeutic index [5]: Margin of safety can be described by considering therapeutics

. It should be first order kinetics. The following figure

represents various formulation strategies for oral CR drug delivery

A STUDY REPORT ON ORAL CONTROLLED DRUG DELIVERY SYSTEM

RAFQUAT RANA, Regd No. -12109112012

FIG- 1: Representation of formulation strategy of oral crdds.

FIG 2: HUMAN DIGESTIVE SYSTEM

A STUDY REPORT ON ORAL CONTROLLED DRUG DELIVERY SYSTEM

RAFQUAT RANA, Regd No. -12109112012

A STUDY REPORT ON ORAL CONTROLLED DRUG DELIVERY SYSTEM

RAFQUAT RANA, Regd No. -12109112012

pH and Volume: pH of the gastric environment affects the performance of orally

of administration affects the performance of oral dosage forms.

A STUDY REPORT ON ORAL CONTROLLED DRUG DELIVERY SYSTEM

RAFQUAT RANA, Regd No. -12109112012

2. Diffusion Controlled drug release system

A STUDY REPORT ON ORAL CONTROLLED DRUG DELIVERY SYSTEM

RAFQUAT RANA, Regd No. -12109112012

6. Osmotic pressure controlled system

1. Dissolution controlled drug release system

Soluble API mixed

FIG 3: Monolithic dissolution controlled system

A STUDY REPORT ON ORAL CONTROLLED DRUG DELIVERY SYSTEM