Introduction

• The basic goals of therapy is to

achieve a steady-state blood or
tissue level that is therapeutically
effective and nontoxic for an
extended period of time.
• This objective can be accomplished
by maximizing drug availability.
• This can be done by increasing the
drug absorption.

Objectives of drug delivery

• The two aspects most important to

drug delivery.
• Spatial Placement:- relates to
targeting a drug to a specific organ
or tissue.
• Temporal Placement:- refers to the
controlling the rate of the drug
delivery to the target tissues.

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Convention Drug therapy

Convention Drug therapy

• Convention drug therapy is of short

duration of action.
• This is due to the inability of
conventional dosage forms to
control temporal delivery..
• If an attempt is made to maintain
drug blood levels in the therapeutic
range for longer period of time
• For e.g. By increasing the dose, then
toxic level may be produced at early
times.

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 Problems with conventional
drug therapy

• If the dosing intervals is not

appropriate for the biological half life
of the drug, large “peaks” and
“valleys” in drug blood level may
results.
• The drug blood level may not be
within the therapeutics range at
sufficiently early time.
• Patient noncompliance with multiple
dosing regimen.

Sustained Release

• The conventional dosage forms

• Dosage form ÆAbsorption poolÆ Target poolÆ
• The rate of absorption is rate limiting step

• Sustained Release
• Dosage form Æ Target poolÆ
• The release of the drug from the dosage from is rate
limiting step.

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 Application

Classification

• No immediate –release delivery

systems may classified as follows:-
• Delayed release
• Sustained release
• Controlled
• Prolonged
• Site specific release
• Receptor release

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• Delayed release:- system uses
repetitive intermitted dosing of
a drug from one or more
immediate release units
incorporated in a single dosage
form.

• Sustained Release:- includes

any drug delivery system that
achieves slow release of drug
over and extended period of
time.

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• Site specific:- targeting the drug
effectively to a certain
biological location.

Potential advantages of
sustained release

• Avoid patient compliance problem

• Employ less total drug
• Minimizing or eliminate local side effects.
• Minimizing or eliminate systemic side effects.
• Minimize drug accumulation.
• Improve the efficiency of the treatment
• Cure or control condition more promptly
• Reduce the fluctuation in drug level.
• Improves bioavailability
• Economy

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Controlled Release:
Art or Science?

dMt
dt

CONTROLLED
t
RELEASE

FORMULATION
dMt
dt

DIFFUSION-CONTROLLED CHEMICALLY-ACTIVATED

Matrix Systems Biodegradable Polymers

Membrane Reservoirs Pendant Chain Chemistry

CONTROLLED
RELEASE

PULSATILE
SOLVENT-ACTIVATED
pH- or Temperature- Sensitive
Swellable Gels Electric or Ultrasonic
Osmotic Systemsrs Multi-Compartmental

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 Swellable Hydrogel
Systems

ξ ξ
Solvent Absorption
Drug

Drug released by diffusion;

Rate controlled by gel mesh space, ξ, and polymer relaxation

Diffusion in Porous Systems

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 Adjusting the Drug Flux
Through Polymers

• Change of the Polymer Structure

(Crosslinking, Crystallinity)
• Change Of Thickness
(Multilaminate Systems)
• Change Of Barriers
(Porosity)
• Change Of Solubility
(Plasticizers)

Adjusting the Drug Flux

Through Polymers

• Change of the Polymer Structure

(Crosslinking, Crystallinity)
• Change Of Thickness
(Multilaminate Systems)
• Change Of Barriers
(Porosity)
• Change Of Solubility
(Plasticizers)

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 3. Solvent-activated controlled

the active agent is dissolved or dispersed within a polymeric matrix and

is not able to diffuse through that matrix.
advantage
˙ complex control
disadvantage
˙ generally more bulky devices and require implantation

Osmotically Controlled
Systems

ƒ Consider Polymer with Drug Incorporated

Throughout
ƒ Presence of Highly Soluble Drug Leads to very
High Osmotic Pressure
ƒ As a Result, the Release System Starts
Rupturing

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 The Oros® System

Elementary Osmotic Pump Cross Section

“Push-Pull” Osmotic
Tablet

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 Osmotic Pump Systems

ƒ Advantages

ƒ Release Rates are Independent of Agent

Properties

ƒ Can Deliver Macromolecules and Ionic Species

ƒ Relatively High Fluxes

ƒ Release Rates are not Dependent on

Environmental Conditions

Osmotic Pump Systems

Disadvantages

ƒ Subject to dose dumping if membrane

breaks
ƒ [e.g. someone chews it]

ƒ Slightly more expensive to formulate

than coating tablets

ƒ Possible hole plugging

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 Targeted Drug Delivery

• Chemotherapy targets all

proliferating cells Æ toxic to
normally dividing cells:
• Bone marrow
• Skin
• GI mucosa

• Purpose:
• Increase drug specificity to
pathological tissue
• Increase drug therapeutic
efficacy
• Decrease systemic toxicity

• Methods:
• Passive targeting Æ Enhanced
Permeability & Retention effect
• Active targeting

Cancer

• In 2000, 1.4 million cases of

cancer
• 560,000 deaths, > 1,500 people
a day
• 1/4 of deaths in US are from
cancer
• Cancer cost:
• $37 billion direct medical costs
• $11 billion low productivity

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• Passive Targeting
• Minimizes non-specific interactions which may lead to
renal excretion or uptake by the reticuloendothelial system
• Utilizes carrier physiochemical characteristics such as size
and hydrophobicity

• Enhanced Permeability and

Retention Effect (EPR)
• Leaky capillaries allow Leaky tumor
extravasation of drug vasculture allows
carriers drug/carrier to
enter
• Deficient lymphatic
system surrounding
tumors leads to
entrapment of large Lower permeability of
molecules within the vasculature in normal Poor
tumor tissue prevents drug lymphatic
carrier from escaping drainage
• Result: passive to areas where it is not traps
accumulation of needed = drug carrier molecules in
molecules the tumor

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