1

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.

2

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.

3

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 Absorption pool Target pool• The rate of absorption is rate limiting step

• Sustained Release• Dosage form Target pool• The release of the drug from the dosage from is rate

limiting step.

4

Application

Classification

• No immediate –release delivery systems may classified as follows:-

• Delayed release• Sustained release

• Controlled• Prolonged

• Site specific release• Receptor release

5

• 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.

6

• 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

7

CONTROLLED

RELEASE

FORMULATION

dMtdt

dMtdt

t

t

Controlled Release:Art or Science?

CONTROLLEDRELEASE

DIFFUSION-CONTROLLED

Matrix SystemsMembrane Reservoirs

CHEMICALLY-ACTIVATED

Biodegradable PolymersPendant Chain Chemistry

SOLVENT-ACTIVATED

Swellable GelsOsmotic Systemsrs

PULSATILE

pH- or Temperature- SensitiveElectric or UltrasonicMulti-Compartmental

8

Swellable Hydrogel Systems

ξSolvent Absorption

Drug released by diffusion;Rate controlled by gel mesh space, ξ, and polymer relaxation

ξDrugDrug

Diffusion in Porous Systems

9

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)

10

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

Consider Polymer with Drug Incorporated Throughout

Presence of Highly Soluble Drug Leads to very High Osmotic Pressure

As a Result, the Release System Starts Rupturing

11

The Oros® System

Elementary Osmotic Pump Cross Section

“Push-Pull” Osmotic Tablet

12

Osmotic Pump Systems

Advantages

Release Rates are Independent of Agent Properties

Can Deliver Macromolecules and Ionic Species

Relatively High Fluxes

Release Rates are not Dependent on Environmental Conditions

Osmotic Pump Systems

Disadvantages

Subject to dose dumping if membrane breaks

[e.g. someone chews it]

Slightly more expensive to formulate than coating tablets

Possible hole plugging

13

Targeted Drug Delivery

• Chemotherapy targets all proliferating cells 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 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

14

• 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

Leaky tumor vasculture allows drug/carrier to enter

Poor lymphatic drainage traps molecules in the tumor

= drug carrier

Lower permeability of vasculature in normal tissue prevents drug carrier from escaping to areas where it is not needed

• Enhanced Permeability and Retention Effect (EPR)• Leaky capillaries allow

extravasation of drug carriers

• Deficient lymphatic system surrounding tumors leads to entrapment of large molecules within the tumor

• Result: passive accumulation of molecules