Drug Delivery

Currently dumb, someday (hopefully) intelligent

David Beebe
Dept. of Biomedical Engineering
 Outline
Intro, terminology, etc.
Methods
Future
 Terminology
Parenteral - other than GI tract (i.e. IV,
subcut., intramuscular, transdermal, etc.)
First pass effect - metabolic breakdown in
the liver
Bioavailability - amount of dose available
to actually do something
 Why drug delivery?
Improve therapy
Improve efficacy, prolong duration, improve
bioavailability, improve targeting, mimic
biopattern
Increase patient compliance
Decrease dose frequency, allow self-admin.
Add competitive advantage (e.g. post drug patent)
New drug $500+ M vs. New delivery system $10-50 M
 Market/Methods/Companies
Oral controlled release largest part of market (~50%)
Gaining are parenteral and implantable types based on
polymers, monoclonal antibodies, liposomes, radioactive
seeds and DNA.
Dry powder inhalers and transdermal patches are also
gaining popularity.
~$40 billion US drug delivery systems market.
Key players include - 3M, Elan, ALZA, Biovail, MiniMed,
RP Scherer, and Andrx.
 Protein Delivery
Major growth area possible because of
recombinant DNA techniques
Applications
Osteoporosis (Calcitonin)
Growth disorders (growth hormones)
Cancer (Interferon)
Diabetes (Insulin)
Barriers
Enzymatic degradation (GI tract)
Membranes (typically proteins traverse membranes via
carrier-mediated process)
 Methods
Oral
Parenteral (IV, etc)
Inhalation
Ocular
Transdermal
Needleless
Implants
Liposomes
 Oral Delivery
90 % of all prescriptions are oral
Controlled release dates to 60s
Protein delivery
Protective coatings (protect from acids,
enzymes)
Permeation enhancers (aid in transport thru
epithelial cells)
 Controlled Release

Sustained Modified

Pulsatile Chrono
 Parenteral
Intravenous
Immediate action
Size/location (>7um trapped in lung, <0.1 um
accumulate in bone marrow, 0.1-7 um taken up by
liver/spleen)
Intramuscular / Subcutaneous
Sustained action
Injected into skeletal muscle / subcut. Tissue
Diffusion limited
 Transdermal Delivery
Skin receives 1/3 of blood
Accessible
Barriers
Permeation
Irritation
Advantages
Avoids first pass metabolism and GI degradation
Ideal for continuous delivery
Improved patient compliance
 Patch Design
Reservoir
Matrix
Drug in adhesive

Iontophoretic - low voltage current drives

movement of charged molecules
Electroporation - high voltage pulses creates pores
Microneedle arrays
 Transdermal

TheraTech
 Inhalation Delivery
Traditionally for respiratory disease
Banning of CFCs created need for redesign
Features
Large surface area
High blood flow
No first pass and low metabolic activity
Non-respiratory disease treatment
Diabetes, cancer, infertility, osteoporosis
 Methods
Nebuliser
Inefficient (1%), large, non-portable
Metered dose inhalers
Inefficient (15%) best case
Difficult to coordinate (inhalation with actuation)
Breath actuated
Dry powder inhalers
No propellant (requires peak inhalation)
 Liposomes
Microscopic vesicles of lipid bilayers
Advantages
Water or oil soluble okay
Biocompatible / degradable
Protect from metabolic degradation
Slow release
 Pumps
Osmotic pumps
Electronic
Insulin Pumps
Two microprocessors, motor/piston,
programmed basal rate
Features
Individual programming
Additional delivery of insulin at
mealtimes or for corrections (bolus)
Temporary increase or decrease of
the basal rate in case of changed
insulin need
The insulin pump does not measure
glucose levels and does not
automatically react to glucose
fluctuations (i.e. its NOT intelligent -
WHY??)
 Next Generation
Intelligent delivery
Detect/sense
Diagnose
Treat
Challenge - requires highly integrated
micro/nano systems
Next Generation
MicroChips

iMedd
 Engineering Organic
Microsystems
Skin (2 cm x 2 cm) a highly integrated system
9 ft blood vessels, 600 pain sensors, 30 hairs,
300 sweat glands, 4 oil glands, 13 yds nerves,
9000 nerve endings, 6 cold sensors, 36 heat
sensors, 75 pressure sensors
Traditional engineering approaches dont
cut it
New approaches needed
 Autonomous Systems
pH Regulation System
 System Design

Input (pH 2)

Outlet (pH 7)

Compensating
Stream (pH 12)
 Autonomous Regulation

13 pH w/ actuator
11 pH w/o actuator
9
pH

1
0 10 20 30 40 50 60 70 80 90 100

time (min)
120
pH 2 buffer flow rate (uL/min)

100

80

60

40

20

0
0 10 20 30 40 50 60 70 80 90 100

time (min)
 Summary
Drug delivery will continue to grow in
importance
Big role for BME
Problems are simple
Solutions are difficult

Will stem cells solve all our problems?

IV. ORAL DRUG DELIVERY SYSTEMS
Oral Controlled-Release Drug Delivery Systems
Coated-Bead Systems
Diffusion Systems
Reservoir Delivery Systems
Other Oral Drug Delivery Systems
Chewable Tablets
Rapid Disintegration Systems
Buccal Systems
Effervescent Systems
Polymer-Based Systems
Miscellaneous Oral Drug Delivery Systems
V. PARENTERAL DRUG DELIVERY SYSTEMS
Infusion Products
IV Administration Sets
IV Pumps & Controllers
IV Catheters
Premixed IV Solutions
Hypodermic Products
Prefilled Syringes
Hypodermic Supplies & Devices
Hypodermic Syringes
Hypodermic Needles
Other Parenteral Drug Delivery Systems
Specialized Parenteral Dosage Formats
Monoclonal Antibodies
Polymers
Liposomes
Gene Delivery Systems
Other Parenteral Supplies & Devices
Hemodialysis Products
Peritoneal Dialysis Products
Enteral Feeding Products
VI. INHALATION DRUG DELIVERY SYSTEMS
Dosage Formulations
Metered Dose Inhalers
Dry Powder Inhalers
Nasal Spray Dispensers
Inhalation Supplies & Devices
Oxygen Therapy Equipment
Oxygen Therapy Supplies
Ventilators
Anesthesia Equipment
Anesthesia Disposables
Nebulizers
VII. TRANSDERMAL & IMPLANTABLE DRUG DELIVERY SYSTEMS
Transdermal Drug Delivery Systems
Transdermal Technologies
Product Applications
Producers & Developers
Implantable Drug Delivery Systems
Pulse Generators
Drug Inserts
Other Implantable Drug Delivery Systems
VIII. DRUG DELIVERY SYSTEMS BY END USE
Respiratory Agents
Central Nervous System Agents
Cardiovascular Agents
Gastrointestinal Agents
Hormones & Related Agents
Anticancer Agents
Nutritional Agents