Controlled and sustained release dosage form/CONTROLLED RELEASE DOSAGE FORM/SUISTAINED RELEASE DOSAGE FORM

1. CONTROLLED AND SUSTAINED RELEASE DOSAGE FORM
INTRODUCTION
1. CONTROLLED RELEASE DOSAGE FORM
• Controlled drug delivery is one which delivers the drug at a
predetermined rate, for locally or systemically, for a specified period
of time.
• Continuous oral delivery of drugs at predictable & reproducible
kinetics for predetermined period throughout the course of GIT.
2. SUSTAINED RELEASE DOSAGE FORM
• Sustained drug delivery may provide an immediate dose required
for the normal therapeutic response, followed by the gradual release
of drug in amounts sufficient to maintain the therapeutic response
for a specific extended period of time usually 8-12 hours.

2. Differences between sustained and controlled drug delivery system
Sustained release dosage form Controlled release dosage form
1. Constitutes dosage form that
provides medication over
extended period of time
2. SRDF generally do not attain
zero order release kinetics
3. Usually do not contain
mechanisms to promote
localization of the drug at
active site.
1. Constitutes dosage form that
maintains constant drug levels
in blood or tissue
2. Maintains constant drug
levels in the blood target
tissue usually by releasing the
drug in a zero order pattern.
3. Controlled dosage forms
contain methods to promote
localization of the drug at
active site.

3. Comparison of Drug Release Profile

4. 1. Diffusion
• Major process for absorption.
• No energy required.
• Drug molecules diffuse from a region of higher concentration to
lower concentration until equilibrium is attained.
• They are of 2 types:
1. Matrix diffusion system 2. Reservoir diffusion system
•The drug is released either by
passing through the pores or
between polymer chains.
•Example- Such as polyehylene,
polyvinylacetate.
•The drug is contained in a core,
which is surrounded by a polymer
membrane, and it is released by
diffusion through rate- controlling
membrane.
• e.g. Poly(N-vinyl pyrrolidone),
Poly(ethylene-co-vinyl acetate).
Mechanism aspects of controlled and Sustained release

5. 2. Dissolution
• It is of 2 types:
1. Matrix Type 2. Encapsulation
•Also called as Monolith dissolution
controlled system.
•Controlled dissolution by:
1.Altering porosity of tablet.
2.Decreasing its wettebility.
3.Dissolving at slower rate.
•First order drug release.
•Drug release determined by
dissolution rate of polymer.
•Examples: Dimetane extencaps.
•Called as Coating dissolution
controlled system.
•Dissolution rate of coat depends
upon stability & thickness of
coating.
•Masks colour, odour, taste,
minimising GI irritation.
•Examples: Ornade spansules.
Soluble drug
Slowly dissolving
matrix
Soluble drug
Slowly
dissolving
or erodible
coat

6. 3. Osmotic Pressure Controlled System
• Provides zero order release
• Drug may be osmotically active, or combined with an osmotically
active salt (e.g., NaCl).
• Semipermeable membrane usually made from cellulose acetate.
• More suitable for hydrophilic drug.
• Examples: Glucotrol XL, Procardia XL.
4. Water penetration (swelling)
• This type of systems are initially dry and when placed in body, absorb
water or other fluid and it swells.
• Swelling increases aq. solvent content within the formulation as well as
the polymer mesh size, enabling the drug to diffuse through the swollen
network into external environment.
• E.g(N-isopro-pylacrylamide), Ethylene-vinyl alcohol

7.  Advantages and disadvantages of controlled release and
sustained release
Advantages Disadvantages
• Total dose is low.
• Reduced GI side effects.
• Reduced dosing frequency.
• Better patient acceptance and
compliance.
• Less fluctuation at plasma drug
levels.
• More uniform drug effect
• Improved efficacy/safety ratio.
• Dose dumping.
• Reduced potential for accurate
dose adjustment.
• Need of additional patient
education.
• Stability problem.
• The physician has less flexibility
in adjusting dosage regimen, as it
is fixed by dosage form design.

8. EXAMPLES OF Controlled and Susatained Release Dosage Forms
1. Transdermal patches
• A transdermal patch is a medicated adhesive patch that is placed on
the skin to deliver a specific dose of medication through the skin and
into the bloodstream. Often, this promotes healing to an injured area
of the body.
Advantages Disadvantages
1. Topical patches are a painless
way to deliver substance
directly into the body.
2. Topical patches are cost
effective , and preferable with
fewer side effect.
3. They are controlled, steady
dellivary of medication over
long periods of time.
1. It cannot achive high drug levels
in blood/plasma.
2. It cannot deliver ionic drugs, and
cannot develop for drugs of
large molecular size.
3. It cannot deliver drugs in a
pulsatile fashion.

9. 2. Implants
• An implant is a medical device manufactured to replace a missing
biological structure, support a damaged biological structure, or
enhance an existing biological structure.
Advantages Disadvantages
1. Convenience- effective
concentration of drug in the
blood can be maintained for
longer period of time.
2. Improved drug delivery- Drug
is distributed in systemic
ciculation with least interference
by metabolic or biological
barrier.
3. Compliance- By allowing
complete elimination, of patient-
involved dosing compliance is
increased.
1. Invasive- to initiate therapy
either a minor or a major surical
procedure is required to initiate
therapy.
2. Danger of device failure- If
device may for some reason
fails to work, it requires surgical
involvement to correct.
3. Limited to potent drug- The
size of implant is small,
therefore implants have potent
medicine like hormones in
limited loading capicity.

10. 3. Liposomes
• Liposomes is an artificial vesicle composed of one or more
concentric phospholipid bilayers and used especially to deliver
microscopic substances to body cells.
Advantages Disadvantages
1. Liposomes are biocompatible,
completely biodegradable, non-
toxic and non-immunogenic for
systemic and non-systemic
administrations.
2. Liposomes are increased
efficacy and therapeutic index of
drug.
3. Liposomes helps to reduce
exposure of sensitive tissue to
toxic drugs.
1. The production cost is high, they
have short half-life
2. Liposomes have low solublity,
leakage and fusion of
encapsulated drug molecules.
3. Sometimes phospholipid
undergoes oxidation and
hydrolysis like reaction.