Course outline

IPPH 363
Basic Pharmaceutics II

Pharmaceutics and drug delivery systems

Powders, capsules, tablets
Polymers
Basics of controlled drug delivery
Mechanisms of controlled drug delivery

Controlled Drug Delivery Systems

Drug administration routes

Drug targeting
Modulated drug delivery (advanced dds)

Fundamentals & Applications

Regulatory considerations

Chapter 1.
Pharmaceutics and Drug Delivery Systems

Drug delivery systems in the global market

Higher profit
Saving in R&D

I. Drug Discovery in Global Economy

Global:

Drug delivery technology

Transportation (a small world)

Communication (phone, fax, e-mail)
Internet

$$53 Billion
(10-25% Annual growth)
(40% of the total market by 2007)

Global competition (made in U.S.A.)

Contract research throughout the world
Contract research organization (CRO)
Contract service organization (CSO)

Mergers between Pharmas:

More blockbuster drugs

M
More
innovation
i
i

$400 Billion

Global Pharmaceutical Industry in 2002

II. Drugs and Economy

II. Drugs and Economy

A. Roles of drugs

A. Roles of drugs

1. Treatment of diseases and illnesses

Infections, hypertension, heart attack, cancers, ulcers, pain

1. Treatment of diseases and illnesses

Infections, hypertension, heart attack, cancers, ulcers, pain

Modern medicine
does not exist
without drugs.

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2. Support of other therapeutic techniques

Surgery (anesthesia)
Organ transplant (immunosuppresseants)
Psychiatry
3. Diagnostic tool
Imaging agents

II. Drugs and Economy

II. Drugs and Economy

B. Criteria for todays drugs

C. Drug development an economic issue

1. Scientific criterion
Effectiveness & safety
2. Economic criterion: prifitability
diseases with high population (cardiac diseases, asthma,
cancer, osteoporosis)
New market with new drugs
No orphan drugs (for diseases with <200,000 in US)
No drugs for orphan diseases (3rd world)

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II. Drugs and Economy

C. Drug development an economic issue
Cost of drug development: $150 M - $1,700 M

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Ii. Drugs and Economy

C. Drug development an economic issue
Cost of drug development: $150 M - $1.700 M
Why drugs are so expensive?
(For human applications)
High development cost
Liability for unforeseen side effects (Vioxx)
Competition by generic drugs
Control of drug cost by government?
Drug development by government

Pharmaceutical companies
are also to be blamed.

If prilosec is such a good

drug, why is the same
company now promoting
Nexium?

III.Drug Discovery

III.Drug Discovery

A. Scientific disciplines in drug

discovery

A. Scientific disciplines in drug discovery

1. Chemotherapy
2. Pharmacology
Experimental pharmacology
Observation, hypothesis, and experiments in animals
Modern pharmacology
Dosage-effect relationship
3. Microbiology and fermentation: penicillin
4. Biochemistry
Isolatioin of enzymes
From cell cultures to chemical processes
Concept of a receptor (receiver for specific stimulus or signal)
Concept of intracellular signal transduction
5. Molecular biology

1. Chemotherapy
Binding of dyes to certain
fabrics & cells
Paul Ehrlich:
not only dyes but also many
chemical molecules have
affinity to tissues, cells, and
cellular components.
1890s: antitoxins (= antibodies)
Magic bullets

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III.

Drug Discovery

III.

Drug Discovery

III.

Drug Discovery

B. Search for new drugs

B. Search for new drugs

B. Search for new drugs

1. Serendipity
(Penicillin)

1. Serendipity
(Penicillin)

1. Serendipity
(Penicillin)

2. Folk medicine
botanical medicine

2. Folk medicine
botanical medicine
3. Rational screening
Allegra (Seldane)
Desloratadine (Claritin)
R-fluoxetine (Prozac)
Cholestrol lowering drugs

III.

Drug Discovery

B. Search for new drugs

1.
2.
3
3.
4.

Serendipity: penicillin
Folk medicine, botanical medicine
Random screening (blind screening)
Rational screening

5. Semirational drug design (target molecule)

6. Fully rational drug design
(Structural data of target molecule)

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III. Drug Discovery

III. Drug Discovery

C. Drug discovery in the past

C. Drug discovery in the past

Edward Jenner (1749-1823)

Concept of vaccination

Edward Jenner (1749-1823)

Concept of vaccination
Louis Pasteur (1822-1895)
Germ theory of disease
(A
(Attenuated
d bacilli)
b illi)

Prevention of smallpox using

cowpox (relatively
( l i l harmless).
h
l )

III. Drug Discovery

III. Drug Discovery

C. Drug discovery in the past

C. Drug discovery in the past

Edward Jenner (1749-1823)

Concept of vaccination
Louis Pasteur (1822-1895)
Germ theory of disease
(A
(Attenuated
d bacilli)
b illi)
Joseph Lister (1867)
Antiseptic, carbolic acid

Edward Jenner (1749-1823)

Concept of vaccination
Louis Pasteur (1822-1895)
Germ theory of disease
(A
(Attenuated
d bacilli)
b illi)
Joseph Lister (1867)
Antiseptic, carbolic acid
Robert Koch (1843-1910)
Bacteria causing anthrax,
tuberculosis, & cholera

III.Drug Discovery

Drug discovery in the past

Edward Jenner (1749-1823)

Concept of vaccination
Louis Pasteur (1822-1895)
Germ theory of disease
(Attenuated bacilli)
Joseph Lister (1867)
Antiseptic, carbolic acid
Robert Koch (1843-1910)
Bacteria causing anthrax,
tuberculosis, & cholera
Paul Ehrlich (1854-1915)
Magic bullet
Sleeping sickness, trypan red
Syphilis, Sarvasan 606

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III.Drug Discovery

III.Drug Discovery
C. Drug discovery in the past

C. Drug discovery in the past

Edward Jenner (1749-1823)

Concept of vaccination
Louis Pasteur (1822-1895)
Germ theory of disease
(Attenuated bacilli)
Joseph Lister (1867)
Antiseptic, carbolic acid
Robert Koch (1843-1910)
Bacteria causing anthrax,
tuberculosis, & cholera
Paul Ehrlich (1854-1915)
Magic bullet
Sleeping sickness, trypan red
Syphilis, Sarvasan 606
Alexander Flemming (1881-1955)
Lysozyme, Penicillin

Edward Jenner (1749-1823)

Concept of vaccination
Louis Pasteur (1822-1895)
Germ theory of disease
(Attenuated bacilli)
Joseph Lister (1867)
Antiseptic carbolic acid
Antiseptic,
Robert Koch (1843-1910)
Bacteria causing anthrax,
tuberculosis, & cholera
Paul Ehrlich (1854-1915)
Magic bullet
Sleeping sickness, trypan red
Syphilis, Sarvasan 606

Synthetic drugs
(sulfa drug, progesteron,
chlorpromazine, imipramine,
clozapine, fluoxetin)

Alexander Flemming (1881-1955)

Lysozyme, Penicillin

III.Drug Discovery
D. Drug discovery & development in the modern era
Pharmacogenesis: process of drug discovery
Drug discovery
1. From plants:
Paclitaxel (yew tree)
2. By synthetic chemistry:
(Combinatorial chem. High throughput scrn)
3. Through biotechnology
(Protein drugs)

III.Drug Discovery
D. Drug discovery & development in the modern era
Observational: wine
(resveratrol: antioxidant, antiplatelet, cancer preventive)
Planned:
T
Tagamet
t (Hi
(Histamine
t i H2-receptor
H2
t antagonist)
t
i t)
High throughput screening
In vitro binding assay (target protein)
Binding to receptors: selectivity
Animal experiments: bioavailability. Toxicity
Animal model for drug screening: flawed (thalidomide)

Genomics

III.Drug Discovery
E. Drug development in the future
Discovery of the DNA Structure (1953)

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Genome:
The entire collection of
Genes in an organism.

Pharmacogenomics:
Genetic variations
determining drug efficacy &
toxicity

Targeted medicine
= Personalized medicine.
Link between
A specific disease and
a genetic variation

Personalized drugs

Pharmacogenetics:

Link between
The generic aberration and
drug that interferes with it.

Breast cancer patients

30% of the patients:
Overabundance of Her2 gene
making receptors for growth
factors.
Growing of cells.
Turning into tumors.

Genetic variations affecting

response to a drug (mainly
drug metabolism)

Old medicine:
Blockbuster drugs
Personalized
medicine:
Smaller market.
But lower failure
rates in drug
development.
All drugs will be
viable to a certain
group of patients.

Personalized medicine:
Propelled by the
deciphering of the human
genome.
There is no such thing as a
human genome.
Infinite range of human
variability.
(DNA evidence in CSI)

Pharmacogenomics

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Info Tech

PROTEOMICS

PROTEOMICS

(PROTEIN CHEMISTRY)

The study of multi-protein

systems.
Focus on the interplay of
multiple, distinct proteins
in their roles as part of a
larger system or network.
network
Complex protein mixtures
Partial sequence analysis
(Database matching)
System biology
(Behavior of the system,
not of any single component)

Iv. Development of Drug Products

Preclinical study
Biological properties
pharmacology, adme, toxicology

NEW CHEMICAL ENTITY

Preformulation studies
Water-solubility
y
Dissolution rate
Physical form
(size, crystalline vs amorphous)
Stability
Partition coefficient
Permeability

PRECLINICAL STUDY

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DRUG ABSORPTION FROM THE GI TRACT

ABSORPTION INTO BLOOD
GI TRACT

DOSAGE
FORM
DISSOLUTION

DRUG IN
SOLUTION

TRANSIT

CLASS II DRUGS
HIGH P, LOW S

V.

DOSAGE FORMS

DOSAGE FORMS = DRUG DELIVERY SYSTEMS (DDS)

V.DOSAGE FORMS

DRUG DELIVERY SYSTEMS

PERIOD CHARACTERISTICS

TECHNOLOGY

50-70

SUSTAINED RELEASE
LOW MOL. WT. DRUGS

WAXES, OILS
ENTERIC COATING

70-90

CONTROLLED RELEASE
ZERO-ORDER RELEASE
DRUG TARGETING

VARIOUS POLYMERS
& HYDROGELS

90-00

MODULATED DELIVERY
PROTEIN DRUGS, GENES

SMART POLYMERS
& HYDROGELS

00-10

DELIVERY OF LOW &

HIGH MOL. WT. DRUGS

CLINICALLY USEFUL
FORMULATIONS

DOSAGE FORMS = DRUG DELIVERY SYSTEMS (DDS)

A. REASONS FOR HAVING VARIOUS DOSAGE FORMS
TO PROVIDE SAFE AND CONVENIENT DELIVERY OF ACCURATE
AMOUNT OF A DRUG TO APPROPRIATE PLACES.
SPECIFIC DOSAGE FORMS DEPENDING ON DRUGS
(PHYSICOCHEMICAL AND OTHER) PROPERTIES
SUSCEPTIBLE TO OXIDATION & HYDRATION (SEALED
AMPULES)
ACID-LABILE (ENTERIC COATED TABLETS)
POSSESSING BITTER TASTE OR OFFENSIVE ORDER
(CAPSULES, COATED TABLETS, FLAVORED SYRUPS)

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V. DOSAGE FORMS

V. DOSAGE FORMS

DOSAGE FORMS = DRUG DELIVERY SYSTEMS (DDS)

C. CONVENTIONAL VS. CONTROLLED RELEASE

DOSAGE FORMS

B. DOSAGE FOR DESIGN

1.
2.
3.
4.
5.
6.

FACTORS TO CONSIDER IN FORMULATION

CONVENTIONAL DOSAGE FORMS

THE DRUG AMOUNT & DURATION OF ACTION

NATURE OF ILLNESS
THERAPEUTIC SITUATION (PREVENTION OR TREATMENT?)
METHOD OF TREATMENT (LOCAL OR SYSTEMIC?)
ROUTE OF ADMINISTRATION (ORAL, TRANSDERMAL, ETC.)
AGE (GERIATRIC, PEDIATRIC, ADULT?)
ANTICIPATED CONDITION OF THE PATIENT
(AWAKE, IN COMA?) (MOTION SICKNESS/VOMITING?)

CONTROLLED RELEASE DDS

DELAYED RELEASE
SUSTAINED RELEASE
REPEAT ACTION
RELEASE KINETICS

DRUG DELIVERY SYSTEMS

PATIENCE COMPLIANCE AND CONVENIENCE
(ONCE-A-DAY, PULMONARY DELIVERY, NEEDLE-FREE DEVICE)

Toxi c r an ge
Ze r o-or d e r r e le a se

Ma x. s a fe con c. (Cmax )
Dru g
co n ce nt .
in b lood

Th e ra peu t ic r an ge
Mi n. e ffe
ff ctt ive
i
r an ge ( Cmini )

Dr u g r e le a se r a t e
fr om con t r o ll ed
r e le a se d osa ge for m s

Dr u g r e le a s e
r a t e (d M/ d t )

INCREASE IN PATENT LIFE AND MARKET SHARE

WITH UNIQUE DRUG DELIVERY SYSTEMS

Non -z er o -o r d er r el ea se

In effect ive ra nge

(Subt h er ap eu t ic r an ge)

Dr u g r e le a se r a t e
fr om con v en t i on a l
d osa ge fo rm s

Tim e

SPECIALIZED FIELD OF PHARMACEUTICAL AND

BIOTECHNOLOGY INDUSTRIES.

Tim e

DRUG DELIVERY INDUSTRY - SYNERGISTIC

PARTNERSHIP WITH PHARMA INDUSTRY

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