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Controlled Release Dosage Forms

Drug delivery systems designed to provide a controlled or delayed release of active

component from the dosage form.

Advantages of controlled release dosage forms are as follows,
1. Minimizes frequent drug administrations.
2. Less fluctuation in drug levels in the body.
3. Better disease control.
4. Steady-state levels are maintained in the body.

Disadvantages include,
1. Variation in drug release.
2. Risk of dose dumping in case of drug released all at once.
3. Difficulty in retrieval of dose in case of toxicity.
4. Variable absorption.

Classification of Controlled release drug delivery systems.

Based on route of administration
A. Oral route: They are further classified as,
I. Continuous release systems: Include the following,
• Matrix type systems: The active ingredient is dispersed in a polymer matrix
which releases the drug slowly with time. The release depends on the matrix
characteristics. The matrix may be Hydrophilic/Hydrophilic, single/multi
layered.
• Reservoir type systems: In such systems, the drug is encapsulated in a film/
membrane which has definite sickness and is rate controlled. The release of
drug depends on the membrane characteristics. Examples are Tablets, pellets,
granules,microencapsulates etc.
II. Gastroretentive systems: These are designed to release the drug specifically in the
GIT over a period of time. They are classified as,
• Floating systems: In these systems, the density of the dosage form is less than
that of the GI fluid causing it to float in the stomach. They are of following
types,

Effervescent systems: Formulated using swellable polymers such as
HPMC, CMC in the core, using citric or tartaric acid , which give rise to
gas during swelling.

Non-effervescent systems: These are formulated using swellable polymers
which expand during swelling.
• Low density systems: These are formulated to be inherently low density, i.e.
before coming in contact with GI fluids. They are formulated by entrapment of
air in volatile liquids (Microspheres) or by using pressure.
• Mucoadhesive systems: The dosage form is formulated using polymers like
Chitosan, which adhere to the gastric mucosa, so that there is extended contact
of the dosage form with GIT.

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III. Time specific systems: They are designed to be time-controlled and

independent of the environment. The examples of such systems are,
• Osmotic systems: These systems consist of a drug layer, an osmagent
(substance that imbibes water swells), a semipermeable membrane and a
delivery orifice. These systems may be formulated as Tablets or capsules.
Examples are,
1. Elementary osmotic pump: Single layer of tablet containing drug and
NaCl (osmagent), encased by SPM containing a laser-drilled delivery
orifice. After coming in contact with water, the osmagent swells and pushes
the drug through the delivery orifice.
2. Osmotic tablets: These may be divided as bilayered osmotic tablet
(containing a lower layer of osmagent and upper layer of drug, the
osmagent swells and pushes the drug from the orifice), trilayered tablet
(contains two drug layers and an osmagent layer at the bottom) etc.
3. Osmotic capsules: The drug is liquid and is present in a gelatin capsule
which is encased by a semipermeable membrane and osmagent. These may
be softgels or hard-gelatin capsules.
IV. Site specific systems: These are usually dependent upon pH, presence of
enzymes, presence of bacterial flora etc to release the drug from the dosage
form.
They are classified as,
• pH dependent systems: Formulated using pH dependent polymers ( which
are soluble at specific pH), such as Eudrajit L or Eudrajit S.
Eudrajit L: Soluble at pH 6, delivers drug in the intestine.
Eudrajit S: soluble at pH 7, delivers drug in the colon/rectum
These systems can also be modified to have a non pH dependent polymer
such as Eudrajit RS in the centre with Eudrajit L/S at the outer layer.
• Enzyme dependent systems: These systems are designed with polymers
that are broken down by enzymes present in the colon/intestine. The
enzymes present are azoreductases, polysaccharidases etc.
Example: Formulation of 5-amino salicylic acid to azo-linked polymer
which is broken down by bacterial azoreductase enzymes to release the
drug into the colon.
B. Transdermal route: These are formulated as patches that are applied over the skin
which release the drug from the skin at a controlled rate, also called as TDDS.
TDDS can be formulated in one of the following ways,

Drug in reservoir systems: The drug and the skin are separated by a rate
controlling membrane, which may be prepared by using poly elastomers,
silicones, polyacrylonitriles etc.

Drug in matrix systems: The drug is dispersed in a polymeric matrix
composed of polyurethanes, polyvinyl alcohol or elastomers.

Drug in adhesive matrix: In this case, the drug is dispersed in a matrix which
possesses adhesive properties for adhering to the skin.

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Microreservoir type system: Combination of reservoir and matrix type of

systems.
TDDS patches contain the following components,
1. Backing membrane: That supports the system.
2. Adhesive layer: A pressure sensitive adhesive layer is coated on top of the
backing membrane.
3. The release liner: It is the topmost layer of drug in a polymer.

C. Parenteral route: These systems are designed to provide controlled release of the drug
by the parenteral route.
These systems are classified as follows,
A. Injectables:
1) Emulsions: Microemulsions or coarse emulsions
2) Suspensions: Microsususpensions or coarse suspensions.
3) Liposomes
4) Nanoparticles: Nanosuspensions or nanoemulsions
5) Microspheres/ Microcapsules

Parenteral systems can also be formulated into implants or osmotic pumps.

Kinetics of Sustained release dosage forms:

Kinetic model Equation Example

Water soluble drugs in porous matrix
First order release
log Q1 = log Q0 + Kt (Drug release proportional to drug
model
concentration)
Osmotic systems, TDDS
Zero order release
ft = K0t ( release independent of
model
concentration)
Higuchi’s equation ft = KHt1/2 Diffusion matrix formulations
Hixson – Crowell
cube root W01/3 – Wt1/3 = Kst Erodible matrix system
equation
Korsmeyer- Peppas’
power Mt/M∞ = Ktn Swellable polymeric systems
Law equation
Peppas - Sahlin Mt/M∞ = Ktm + Kt2m Swellable polymeric systems
3/2 [1 – (1 – Mt/M∞)2/3] –
Baker - Londsdale Microspheres or microcapsules
Mt/M∞ = Kt

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