4 Principles of Pharmacology Methods of Drug Delivery
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Course
Pharmacology
Institution
Pharmacology
The object of the course is to teach students an approach to the study of pharmacologic agents. It is not intended to be a review of the pharmacopoeia. The focus is on the basic principles of biophysics, biochemistry, and physiology as to the mechanisms of drug action, biodistribution and metabolis...
Harvard-MIT Division of Health Sciences and Technology
HST.151: Principles of Pharmocology
Instructor: Prof. Robert Langer
R. Langer/HST-151 1
Methods of Drug Delivery
Professor Robert Langer, D. Sc.
I. Introduction:
The means by which a drug is introduced into the body is almost as important as
the drug itself. Drug concentration at the site of action must be maintained at a
level that provides maximum therapeutic benefit and minimum toxicity. The
pharmaceutical developer must also consider how to transport the drug to the
appropriate part of the body and, once there, make it available for use.
As the name implies, a controlled-release drug delivery system serves two
functions:
1. Drug delivery, involves the absorption and transport of the drug to a particular
part of the body. This may be accomplished intravenously, transdermally,
orally, by implantable reservoir, etc.
2. Controlled release governs the rate at which the drug is made available to the
effect site once it has been delivered.
Traditionally, delivery systems have not incorporated means of controlled release.
This means that the concentration of most drugs peaks and declines rapidly after
each dose and will often be above or below the desired therapeutic range.
Plasma Drug Level
Desired
Range
Time
Next Dosage
,R. Langer/HST-151 2
II. Sustained Release
Sustained release is an incremental improvement. It provides prolonged but not uniform
release of drug and reduces the need for repeated dosing. Once the maximal level is
reached, the amount of drug in the body decreases slowly so it will take longer to drop
below the therapeutic range. Sustained release technologies in current use include
1. Complexes
2. Slowly dissolving coatings
3. Suspensions
4. Emulsions
5. Compressed tablets
Release rates are strongly influenced by environmental conditions
Release rarely lasts longer than 12 hours; so the benefits are limited.
Plasma Drug Level
Desired
Range
Time
, R. Langer/HST-151 3
III. Controlled Release
This is a substantial advance over sustained release. Technologies include
1. Polymers
2. Pumps
Weakly influenced by local environment (fixed release pattern)
Release can occur over long periods
Pl
as
ma
Dr
ug
Le
Plasma Drug Level
vel
Desired Range
Time
Time
IV. Targeted (Controlled) Release
Controlled release technology designed to maintain relatively high concentrations at a
specific site. Techniques include
1. Liposomes
2. Microspheres and microcarriers
3. Drug-carrier complexes (pendant systems)
V. What is driving growth of this technology?
Consider U.S. Annual Statistics
1. Adverse Drug Effects
15% of hospital admissions
100,000 deaths
$136 billion in health care costs
2. Patient Compliance
10% of hospital admissions
3. 2001 Sales of Drug Delivery Systems
$20 billion
Multiple incentives for manufacturers to use controlled release:
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