7/30/2019 1 IntroDDS(a)

1/22

Controlled Drug Delivery Systems:

An Overview of the Field

Prof. Allan S. Hoffman, ScD.

Bioengineering DepartmentUniversity of Washington

Seattle WA, 98195, USA

7/30/2019 1 IntroDDS(a)

2/22

Thereisgreatinterestaroundthe

worldinthedrugdelivery field.

7/30/2019 1 IntroDDS(a)

3/22

Itis oneofthemost activeareasof

R&Dinpolymericbiomaterials.

7/30/2019 1 IntroDDS(a)

4/22

Sign if ican t drug del ivery sys tems (DDS)

developed from the 1970s to the present

Transdermal patches

Implanted, drug-loaded, degradable microparticles

Soluble polymer-drug conjugates

Osmotic pressure-driven capsules for oral DD

Implanted, drug-loaded silicone rods

Special inhalers for pulmonary DD

Colon-specific DDS

Enteric coatings for oral tablets

Drug-loaded polymer coatings for stents

Stealth liposomes

7/30/2019 1 IntroDDS(a)

5/22

Tissue engineering implants are an

emerging application of drug delivery!

7/30/2019 1 IntroDDS(a)

6/22

First, a few words about the

principles for designing a drugdelivery system based on how and

where the drug will act in the body.

7/30/2019 1 IntroDDS(a)

7/22

To design a DDS it is important to know

how much drug is needed?

at what delivery rate?

over what period of time (duration)?

with what bioavailability?

acting at which sites or on which cells?

7/30/2019 1 IntroDDS(a)

8/22

In the c ircu lat ion

In the tissue space (ECM)

At the cel l membrane

Ins ide the cel l

Where do drugs act in the body?

7/30/2019 1 IntroDDS(a)

9/22

The Dose-Effect Relationship

Pharmacokinetics

Dose

Plasma Concentration

Pharmacodynamics

Effect

(PK)

(PD)

7/30/2019 1 IntroDDS(a)

10/22

The Dose-Effect Relationship

Pharmacokinetics

Dose

Plasma Concentration

Pharmacodynamics

Effect

(PK)

(PD)

Dont forget--every person has

a different dose-effect with each

drug and dosetherefore, a large

population is needed to design aneffective dosage formulation.

7/30/2019 1 IntroDDS(a)

11/22

L. Maggi, U. Conti,

Geomatrix Technology,

Segno & Forma, 2003

7/30/2019 1 IntroDDS(a)

12/22

Pharmacokinetics / Pharmacodynamics

0

1

2

3

4

5

6

7

0 5 10 15 20 25

Time

Drug

Conc

entration

Pharmacokinetics (PK)

What the body does to the

drug

Fairly easy to measure

(e.g., biodistribution)

Used to get to the PD

Pharmacodynamics (PD)

What the drug does to the

body

Less well understood

PD has clinical relevance

0

0.5

1

1.5

2

2.5

3

3.5

0 2 4 6 8 10

Drug Concentration

D

rugE

ffect

Absorption and Distribution

Metabolism and Elimination

Drug effect

Drug concn.

Drug

concn.

in

blood

Time

ADME Large population

7/30/2019 1 IntroDDS(a)

13/22

Pharmacokinetics of Pills and Shots

vs. Controlled Drug Delivery

(pi l ls or in ject ion s)

Drug wasted below range (TI)

Toxicity possible above range (TI)

Con trol led release also results in better pat ient compliance!Cour tesy of Prof. Emo Chiell in i

Also

Therapeutic

Index (TI)

7/30/2019 1 IntroDDS(a)

14/22

CONTROLLED RE LEASE SYSTE MS

Rationale forCont ro l ledRelease of Drugs

In cr eas ed pat ient c om pl ianc e

less frequent dosing

more acceptable (eg, needle-less)

Safety

can control PK to remain within Therapeu

Index window

Im pro ved ther ap ycan time release

environmentally-responsive systems

Dec rease d cos t

lower doses->more efficient use of drug

Gr eate r p ro fit s

patent extension for drug

controlled release feature more profitable

Therapeutic

controlled release feature more profitable

7/30/2019 1 IntroDDS(a)

15/22

An example of economic rationale for controlled release

7/30/2019 1 IntroDDS(a)

16/22

Harvard Health Letter

July 2004

Another example of potential profitability of controlled release

7/30/2019 1 IntroDDS(a)

17/22

Harvard Health Letter

July 2004

7/30/2019 1 IntroDDS(a)

18/22

Some Unso lved Prob lems w ith DDS

Oral delivery of proteins Effective delivery of low solubility drugs

Feedback DDS using body signals to stimulate

delivery of specific amount of drug

Chrono-DDS, delivery based on known circadianrhythms of body organs (perhaps

combined with Feedback DDS)

Pharmacogenomics, drug indications and

prescriptions based on ones geneticmakeup (many ethical issues)

A.S. Hoffman, UW, Seattle, WA

7/30/2019 1 IntroDDS(a)

19/22

How would you design anoverview lecture on drug delivery

systems (DDS)? There are many

different possibilities

7/30/2019 1 IntroDDS(a)

20/22

Des ign o f Drug Del ivery Sys tems (DDS)

This lectu recou ld beorganized accord ing to :

ROUTES OF DELIVERY

(eg, Oral, Injected, Transdermal...)BODY SITE OF DELIVERY

(eg, Blood, Liver, Lungs, Pancreas)

LOCAL SITE FOR ACTION(eg, Body Fluids, Cell Surface, Intracellular)

MECHANISM OF DEL IVERY

(eg, Drug Diffusion, Swelling, Degradation..)DISEASE

(eg, Cancer, Glaucoma, Diabetes..)

7/30/2019 1 IntroDDS(a)

21/22

Des ign o f Drug Del ivery Sys tems (DDS)

This lectu rew i ll beorganized accord ing to :

ROUTES OF DELIVERY

(eg, Oral, Injections, Transdermal...)BODY SITE OF DELIVERY

(eg, Blood, Liver, Lungs, Pancreas)

LOCAL SITE FOR ACTION(eg, Body Fluids, Cell Surface, Intracellular)

MECHANISM OF DEL IVERY

(eg, Drug Diffusion, Swelling, Degradation..)DISEASE

(eg, Cancer, Glaucoma, Diabetes..)

7/30/2019 1 IntroDDS(a)

22/22

Routes of Drug Delivery

OralGastric, enteric, colonic

In ject ion s and ImplantsIntra-venous (IV), sub-cutaneous (SQ),intra-muscular (IM), intra-epidural (IE),

intra-cranial (IC)

TransdermalSkin

Mucosal

Ophthalmic, nasal, vaginal, anal, buccal, sub-lingual

Inhalat ionPulmonary