Drug Delivery Considerations
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Transcript of Drug Delivery Considerations
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IPPH 363
Basic Pharmaceutics II
Controlled Drug Delivery Systems
Fundamentals & Applications
Course outline
Pharmaceutics and drug delivery systems
Powders, capsules, tablets
Polymers
Basicsof controlled dru deliver
Mechanisms of controlled drug delivery
Drug administration routes
Drug targeting
Modulated drug delivery (advanced dds)
Regulatory considerations
Chapter 1.Pharmaceutics and Drug Delivery Systems
I. Drug Discovery in Global Economy
Global: Transportation (a small world)
Communication (phone, fax, e-mail)
Global competition (made in U.S.A.)
Contract research throughout the world
Contract research organization (CRO)
Contract service organization (CSO)
Drug delivery systems in the global market
$53 Billion
Drug delivery technology
Global Pharmaceutical Industry in 2002
$400 Billion
(10-25% Annual growth)(40% of the total market by 2007)
Mergers between Pharmas:
Higher profit
Saving in R&D
More blockbuster drugs
More innovation
II. Drugs and Economy
A. Roles of drugs
1. Treatment of diseases and illnesses
Infections, hypertension, heart attack, cancers, ulcers, pain
Modern medicine
does not existwithout drugs.
II. Drugs and Economy
A. Roles of drugs
1. Treatment of diseases and illnesses
Infections, hypertension, heart attack, cancers, ulcers, pain
2. Support of other therapeutic techniques
Surgery (anesthesia)
Organ transplant (immunosuppresseants)
Psychiatry
3. Diagnostic tool
Imaging agents
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II. Drugs and Economy
B. Criteria for todays drugs
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
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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
A. Scientific disciplines in drug
discovery
1. Chemotherapy
Binding of dyes to certainfabrics & cells
Paul Ehrlich:
not only dyes but also many
chemical molecules haveaffinity to tissues, cells, and
cellular components.
1890s: antitoxins (= antibodies)
Magic bullets
III.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 enzymesFrom cell cultures to chemical processes
Concept of a receptor (receiver for specific stimulus or signal)
Concept of intracellular signal transduction
5. Molecular biology
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III. Drug Discovery
B. Search for new drugs
1. Serendipity
(Penicillin)
III. Drug Discovery
B. Search for new drugs
1. Serendipity
(Penicillin)
2. Folk medicinebotanical medicine
III. Drug Discovery
B. Search for new drugs
1. Serendipity(Penicillin)
2. Folk medicine
botanical medicine
3. Rational screeningAllegra (Seldane)Desloratadine (Claritin)R-fluoxetine (Prozac)
Cholestrol lowering drugs
III. Drug Discovery
B. Search for new drugs
1. Serendipity: penicillin
2. Folk medicine, botanical medicine.
4. 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
C. Drug discovery in the past
Edward Jenner (1749-1823)Concept of vaccination
Prevention of smallpox using
cowpox (re at ve y armess).
III. Drug Discovery
C. Drug discovery in the past
Edward Jenner (1749-1823)Concept of vaccination
Louis Pasteur (1822-1895)
Germ theory of disease
( ttenuate ac )
III. Drug Discovery
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
III. Drug Discovery
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 acidRobert 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
Joseph Lister (1867)
Antiseptic, carbolic acid
Robert Koch (1843-1910)Bacteria causing anthrax,
tuberculosis, & cholera
Paul Ehrlich (1854-1915)
Magic bullet
Sleeping sickness, trypan redSyphilis, Sarvasan 606
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III.Drug Discovery
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)
,
Robert Koch (1843-1910)Bacteria causing anthrax,
tuberculosis, & choleraPaul Ehrlich (1854-1915)
Magic bullet
Sleeping sickness, trypan redSyphilis, Sarvasan 606
Alexander Flemming (1881-1955)
Lysozyme, Penicillin
III.Drug Discovery
C. Drug discovery in the pastEdward Jenner (1749-1823)
Concept of vaccinationLouis 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 bulletSleeping sickness, trypan redSyphilis, Sarvasan 606
Alexander Flemming (1881-1955)
Lysozyme, Penicillin
Synthetic drugs
(sulfa drug, progesteron,
chlorpromazine, imipramine,clozapine, fluoxetin)
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:
agame s amne -recep or an agon s
High throughput screening
In vitro binding assay (target protein)
Binding to receptors: selectivity
Animal experiments: bioavailability. Toxicity
Animal model for drug screening: flawed (thalidomide)
III.Drug Discovery
E. Drug development in the futureDiscovery of the DNA Structure (1953)
Genomics
Genome:
The entire collection of
Genes in an organism.
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Pharmacogenomics:
Genetic variationsdetermining drug efficacy &
toxicity
Personalized drugs
Pharmacogenetics:
Genetic variations affectingresponse to a drug (mainly
drug metabolism)
Targeted medicine
= Personalized medicine.
Link between
A specific disease anda genetic variation
The generic aberration and
drug that interferes with it.
Breast cancer patients
30% of the patients:
Overabundance of Her2 genemaking receptors for growth
factors.
Growing of cells.
Turning into tumors.
Old medicine:
Blockbuster drugs
Personalized
medicine:
Smaller market.
But lower failure
Info Tech
rates in drugdevelopment.
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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PROTEOMICS(PROTEIN CHEMISTRY)
The study of multi-protein
systems.
Focus on the interplay of
multiple, distinct proteins
in their roles as part of a
.
Complex protein mixtures
Partial sequence analysis(Database matching)
System biology(Behavior of the system,
not of any single component)
PROTEOMICS
Iv. Development of Drug Products
NEW CHEMICAL ENTITY
PRECLINICAL STUDY
Preclinical study
Biological properties
pharmacology, adme, toxicology
Preformulation studiesWater-solubilitDissolution rate
Physical form(size, crystalline vs amorphous)
StabilityPartition coefficientPermeability
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DRUG ABSORPTION FROM THE GI TRACT
GI TRACT
ABSORPTION INTO BLOOD
DRUG IN
SOLUTIONTRANSITDISSOLUTION
FORM
CLASS II DRUGS
HIGH P, LOW S
V. DOSAGE FORMS
DOSAGE FORMS = DRUG DELIVERY SYSTEMS (DDS)
DRUG DELIVERY SYSTEMS
PERIOD CHARACTERISTICS TECHNOLO GY
50-70 SUSTAINED RELEASE WAXES, OILS
L OW MO L. WT . D RU GS E NT ER IC CO AT IN G
70-90 CONTROLLED RELEASE VARIOUS POLYMERS
ZE RO -O RD ER RE LE AS E & HYD RO GE LS
DRUG TARGETING
90-00 M ODULATED DELIVERY SMART POLYM ERS
PROTEIN DRUGS, GENES & HYDROGELS
00-10 D ELI VE RY O F L OW & C LI NI CA LL Y U SE FU L
H IG H M OL . WT . D RU GS FO RM UL AT IO NS
V.DOSAGE FORMS
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 (SEALEDAMPULES)
ACID-LABILE (ENTERIC COATED TABLETS)POSSESSING BITTER TASTE OR OFFENSIVE ORDER
(CAPSULES, COATED TABLETS, FLAVORED SYRUPS)
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V. DOSAGE FORMS
DOSAGE FORMS = DRUG DELIVERY SYSTEMS (DDS)
B. DOSAGE FOR DESIGN
FACTORS TO CONSIDER IN FORMULATION
1. NATUREOFILLNESS2. THERAPEUTIC SITUATION (PREVENTION OR TREATMENT?)
3. METHOD OF TREATMENT (LOCAL OR SYSTEMIC?)4. ROUTE OF ADMINISTRATION (ORAL, TRANSDERMAL, ETC.)
5. AGE (GERIATRIC, PEDIATRIC, ADULT?)6. ANTICIPATED CONDITION OF THE PATIENT
(AWAKE, IN COMA?) (MOTION SICKNESS/VOMITING?)
V. DOSAGE FORMS
C. CONVENTIONAL VS. CONTROLLED RELEASE
DOSAGE FORMS
CONVENTIONAL DOSAGE FORMS
THE DRUG AMOUNT & DURATION OF ACTION
CONTROLLED RELEASE DDS
DELAYED RELEASE
SUSTAINED RELEASE
REPEAT ACTION
RELEASE KINETICS
Toxic range
Max. safe conc. (Cmax )
Therapeu t i c rangeDrugconcen t .i n b lood
Ineffective range
(Sub therapeu t i c range)
Time
Min . ef fect ive r ange (Cmin )
Zero-order release
Drug release
} Drug release ratefrom control ledrelease dosage forms
Time
Drug release rate
from conventionaldosage forms
ra t e (dM/ d t )
Non -zer o-o rd er relea se
DRUG DELIVERY SYSTEMS
PATIENCE COMPLIANCE AND CONVENIENCE(ONCE-A-DAY, PULMONARY DELIVERY, NEEDLE-FREE DEVICE)
INCREASE IN PATENT LIFE AND MARKET SHAREWITH UNIQUE DRUG DELIVERY SYSTEMS
SPECIALIZED FIELD OF PHARMACEUTICAL ANDBIOTECHNOLOGY INDUSTRIES.
DRUG DELIVERY INDUSTRY - SYNERGISTICPARTNERSHIP WITH PHARMA INDUSTRY