CONTROL RELEASE DRUG

DELIVERY SYSTEM
PRESENTED BY-

Hatasha Vaddadi
M.Pharm 1st year,
School of Pharmacy, Parul University
GUIDED BY,
Bhargavi Mistry
Ass. Professor, Pharmaceutics
School of Pharmacy, Parul University

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CONTENTS
o Introduction
o Advantages
o Disadvantages
o Factors affecting CRDDS
o Desired characters for CRDDS
o Classification

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 CONTROLLED RELEASE DRUG DELIVERY SYSTEM
o Delivers the drug at a
predetermined rate
o To achieve prolong effect
o Implies predictability in drug
release kinetics
o Basic objective is to maintain
steady state therapeutic
concentration of drug in the
blood or tissue for an extended
period

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 A. Single Dose
B. Double Dose
C. Intravenous Dose
C D. Controlled Release

Toxic Level

Drug Concentration in Blood

D
B

Minimum
Effective
Level

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Time(h) 4
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ADVANTAGES
o Reduction in frequency of drug administration
o Improved patient compliance
o Reduction in drug level fluctuation in blood
o Reduction in total drug usage when compared with conventional therapy
o Reduction in drug accumulation with chronic therapy
o Reduction in drug toxicity (local/systemic)
o Stabilization of medical condition (because of more uniform drug levels)
o Improvement in bioavailability of some drugs because of spatial control
o Economical to the health care providers and the patient

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DISADVANTAGES

o Delay in onset of drug action

o Costly
o Possibility of dose dumping in the case of a poor formulation strategy
o Increased potential for first pass metabolism
o Greater dependence on GI residence time of dosage form
o Possibility of less accurate dose adjustment in some cases
o Cost per unit dose is higher when compared with conventional doses
o Not all drugs are suitable for formulating into ER dosage form
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FACTORS INFLUENCING THE DESIGN OF CRDDS

Drug related Biological

Pharmacokinetic

Others Physiological

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 Aqueous solubility
Protein binding

DRUG
RELATED Partition coefficient
FACTORS

Molecular size

Drug Stability

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o AQUEOUS SOLUBILITY- A drug with good aqueous is a good candidate
for CRDDS.
o PROTEIN BINDING- Drugs which have high protein binding capacity, need
special attention while formulating due to their protein binding ability,
they have prolonged duration of action.
o MOLECULAR SIZE- Drugs with larger molecular size ( >600 daltons ) are
poor candidates for CRDDS.
Ex- proteins and peptides.
o DRUG STABILITY- The drug should be stable for a sufficient duration of
time for which the delivery system has to remain within the body.
Eg Rabeprazole get degraded within 72 seconds in acidic pH of the stomach
o PARTITION COEFFICIENT- Drugs having low oil/water partition coefficient
cannot penetrate the membranes.

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BIOLOGICAL FACTORS AFFECTING CRDDS

Margin of
safety

Distribution

Side effects Elimination

Duration of Absorption
action
Disease
state
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o ABSORPTION- It is necessary that the rate of release is much slower than
the rate of absorption, the drug with slow absorption is a poor candidate
for CRDDS.
o DISTRIBUTION OF DRUG- Volume of Distribution affects the
concentration and the amount of the drug circulating in blood.
o DURATION OF ACTION- ideal CRDDS is one from which rate of drug
absorption is equal to rate of elimination.
t½ = 2-4 hrs would be the best candidate for CRDDS.
o MARGIN OF SAFETY- Drug to be formulated into CRDDS,its margin of
safety should be very high.
o ADVERSE EFFECTS- Side effects can be minimized by controlling the
concentration at which the drug exists in plasma at any given time, and
hence, controlled release formulations appear to offer a solution to this
problem.
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 FPM

DOSE
OCCUPANCY
DUMPING
TIME

PHARMACOKINETIC
PROPERTIES

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o DOSE DUMPING- Dose Dumping takes place when more than the
planned amount of the drug specified for the product is released per unit
time.
o OCCUPANCY TIME- The time during which the plasma concentration
stays within the therapeutic range, becomes an important criterion for
the evaluation for the controlled release formulation.

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Variability on GI emptying
and motility Rate of metabolism

PHYSIOLOGICAL
FACTORS

Food effects

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o GASTRIC EMPTYING- Influences the viscosity of stomach contents as well as
pH and temperature.
eg- Gastric emptying inhibited by anticholinergics and narcotic analgesics
while enhanced by metoclopramide.
A meal with high fat content has been shown to increase the rate and extent
of bioavailability of the controlled release preparations of theophylline.
o RATE OF METABOLISM- Drugs which are extensively metabolize by lives are
suitable candidates for CRDDS as long as the rate of metabolism is not too
rapid.
Metabolism should be predictable. It should not change with a change
in route of administration
o DRUG pKa -The drugs which are extensively ionized are poor candidates for
CRDDS.
Eg- Hexamethanium
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 OTHER FACTORS INFLUENCING CRDDS
o MECHANISM AND SITE OF ABSORPTION- Drugs absorbed by carrier-
mediated transport and drugs having absorption window are poor
candidates for CRDDS.
Eg. Vitamins

o COMPATIBILITY- Ramipril, an antihypertensive drug is incompatible with

almost all the excipients used in the formulation of controlled release
dosage forms.
o ROUTE OF ADMINISTRATION – In Transdermal Route First-pass
metabolism is avoided.

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CHARACTERISTICS THAT MAY MAKE A DRUG
UNSUITABLE FOR CONTROL RELEASE DOSAGE
FORM
o Short elimination half-life3, 4, 5.
o Long elimination half-life
o Narrow therapeutic index
o Poor absorption
o Active absorption
o Low or slow absorption
o Extensive first pass effect

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 Encapsulation Matrix

Reservoir and Environment

Monolithic Responsive
Matrix Chemically
Dissolution Controlled Controlled
Reservoir Diffusion
Controlled

Diffusion Controlled Hydrogels

Swelling
Cation Controlled Release Controlled
Exchange Systems
Ion-exchange Water Penetration
Resins Controlled
Anion
Exchange
Diffusion and Chemically Osmotically Swelling
Controlled Controlled
Dissolution Controlled
Controlled
Drug Covalently
Erodible linked with
Systems polymer

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1. DIFFUSION CONTROLLED RELEASED SYSTEM
(diffusion through membrane)

A. RESERVOIR SYSTEM
o Therapeutic agent is contained in a core surrounded by a thin polymer
membrane and the active agent is released to the surrounding
environment by diffusion process.
o The drug delivery rate remains fairly constant
o Polymer is the rate controlling material
o Chance of dose dumping and it might be dangerous
o Polymers used –ethyl cellulose, polyvinyl acetate

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B. MATRIX SYSTEM
o Also known as porous / monolithic matrix delivery system
o Therapeutic agent is dispersed in a polymer matrix and drug release is
controlled by its diffusion from the matrix into the surrounding
environment
o Polymers uses are -polyvinyl chloride[ rigid polymer]
HPMC, gums [Swellable polymers]
o No danger of dose dumping
o Delivery rate decreases with time

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C. COMBINED TYPE
o It has 2 phases; 1st is outer membrane which is a matrix and the
2nd which a reservoir .
o Initially the release rate of diffusion is through the phase 1 as the
time progresses a layer depleted from the active agent is
generated in phase 2 matrix reservoir material immediatedly
adjacent to the membrane.

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2. DISSOLUTION CONTROLLED RELEASE SYSTEM

A. ENCAPSULATION DISSOLUTION CONTROL

o Coating of individual particles of drug with slow dissolving materials
o Coated materials directily compressed into tablets or capsules
o Coating thickness determine the time required for dissolution.

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2. MATRIX DISSOLUTION CONTROL
o The rate of penetration of dissolution fluid into the matrix
determines the drug dissolution and subsequent release.

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 3. DIFFUSION AND DISSOLUTION CONTROLLED SYSTEM

o Dissolution of the outer membrane leads to

facilitated diffusion of the contained drug
through pores in the coating.
o Fraction of soluble drug in the coationg
material is the release rate controlling factor
o Eg KCl, it cause GI irriatation hence
formulationg this may minimizes irritation

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4. WATER PENETRATION CONTROLLED
(rate control is obtained by the penetration of water into the system)

A. SWELLING CONTROLLED
SYSTEM
When placed in the body absorb water or
other body fluids and swell

As the swelling increases the aqueous

solvent content and polymer mesh size also
increases

This enables the drug to diffuse into the

external environment 12/26/2023 27
B. OSMOTICALLY REGULATED SYSTEMS
The device consists of a rigid housing containing osmotic agent by a
movable piston

One wall of rigid housing is composed of semi permeable membrane

On aqueous exposure, water is driven osmotically by the semi permable

membrane

Increase in vol within osmotic compartment

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 Which in turn exerts pressure in moveable piston

Piston forces the therapeutic agent to move out the osmotic pump

Osmotic pump
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5.CHEMICALLY CONTROLLED SYSTEMS
o Delivery system that change their chemical structure , when exposed to
biological milieu.
MECHANISM OF POLYMER EROSION
o Conversion of water insoluble material into soluble ones by a chemical
degradation
o This is basically of 3 types:
I. Type 1- 3D formed by water soluble macromolecules are eroded at
cleavage or disintegration takes place
II. Type 2-conversion into water insoluble macromolecule by hydrolysis
III. Type 3- change in molecular weight of higher insoluble
macromolecules into soluble ones
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Type 2

Type 3

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DIFFERNET DRUG RELEASE MECHANISM

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6. HYDROGELS
o Hydrogels are water swollen 3D structures composed of primarily
hydrophilic polymers
o They are rendered insoluble because of chemical and physical crosslink
and these cross links are of weak forces which provide physical integrity
and network structure .

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CLASSIFICATION OF HYDROGELS
o Swelling controlled hydrogel systems
o Chemically controlled hydrogel systems
o Environmental responsive systems hydrogel systems
o Diffusion controlled hydrogel systems

Reservoir system
Matrix system

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ENVIRONMENTAL RESPONSIVE HYDROGEL SYSTEM

o The changes in network structure in response to external environment is

reversible in nature

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7. ION EXCHANGE RESINS
Rate is proportional to the concentration of the ions present in
the vicinity of the administration site.

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 TYPES OF ION EXCHANGE
ANION EXCHANGE RESIN
o Involve basic functional groups
capable of extracting anions from
the acidic solutions.
o Strong anion exchanger-Quaternary
ammonium groups attached to a
styrene and divinyl benzene
copolymer
o Weak anion exchanger-
Polyalkylamine groups linked to a
styrene and divinyl benzene
copolymer
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CATION EXCHANGE RESIN
o Contain acidic function groups
like –OH, -COOH
o Strong cation exchanger- sulfonic
acid groups attached to a styrene
and divinyl benzene
copolymer
o Weak cation exchanger –
carboxylic acid groups linked to
an acrylic acid and divinyl
benzene co polymer
37
CONCLUSION
(present status and future prospects )

o Controlled drug delivery systems are developed to combat the problems

associated with conventional drug delivery
o Employment to different polymers and coating systems, different route
of administration
o Market establishment
o Highly potent drugs which have a very narrow margin of safety should
not be used in CRDDS
o Drugs with short half-lives require frequent dosing in order to minimize
fluctuations in blood levels accompanying conventional oral dosage
regimens an are ideal candidates for controlled release dosage form.

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REFERNCE
1. Journals and articles
Https://www.Thepharmajournal.Com/archives/2012/vol1issue1
0/parta/3.1.Pdf
Https://www.Mdpi.Com/1420-3049/26/19/5905
Https://www.Ncbi.Nlm.Nih.Gov/pmc/articles/PMC3407637/#:~:
text=osmotically%20controlled%20drug%20delivery%20systems
&text=it%20is%20driven%20by
2. Books
• Controlled drug delivery concepts and advances by suresh P
vyas and Roop K Khar
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THANK YOU

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