drug delivery considerations

7/24/2019 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.


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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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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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


1. Serendipity

(Penicillin)

2. Folk medicinebotanical medicine

III. Drug Discovery


1. Serendipity(Penicillin)

2. Folk medicine

botanical medicine

3. Rational screeningAllegra (Seldane)Desloratadine (Claritin)R-fluoxetine (Prozac)

Cholestrol lowering drugs

III. Drug Discovery


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



Louis Pasteur (1822-1895)

Germ theory of disease

( ttenuate ac )

III. Drug Discovery





(Attenuated bacilli)

Joseph Lister (1867)

Antiseptic, carbolic acid

III. Drug Discovery





(Attenuated bacilli)


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




Antiseptic, carbolic acid

Robert Koch (1843-1910)Bacteria causing anthrax,


Paul Ehrlich (1854-1915)

Magic bullet

Sleeping sickness, trypan redSyphilis, Sarvasan 606


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III.Drug Discovery



Louis Pasteur (1822-1895)Germ theory of disease

(Attenuated bacilli)Joseph Lister (1867)

,


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



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


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


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

drug delivery considerations

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