PHARM.

DOSAGE FORMS PRELIMS

PHARMACEUTICS201 - LEC
AND MEDICAL DEVICES
LECTURE | FIRST SEMESTER

CHAPTER 1: INTRODUCTION TO DRUGS AND PHARMACY

OBJECTIVES: 5. Expectorant
a. Mucolytic – it thins mucus
1. To define and explain drugs and some of
i. Carbocisteine
its major categories
ii. Acetylcysteine
2. To account on the history of drug
iii. Bromhexine
discoveries
b. Antitussive – for dry cough
3. To identify contemporary roles of
i. Dentromerate
pharmacist
ii. Butamirate citrate (sinecod)
6. Anti-Infectives
DRUGS 7. Cathartics / Laxatives
a. Constipation
• An agent used for the diagnosis, mitigation, b. Bisacodyl (Dulcolax)
treatment, cure or prevention of disease in c. Sema (Senokot)
humans and other animals. 8. Analgesics – allerates pain
9. Anti-pyrectics – lowered body temperature
DRUG CATEGORIES 10. Alkanizers
11. Hyperglycemic
a. Metformin
1. Cardiotonic - Opposing effect (Mydriatic –
12. Hypoglycemic
Miotic)
a. Decreses the level pf glucose
a. Mydriatic – dilation of pupils of the
13. Hyperlipidimic
eye
a. Increased lipids
i. Atropine
b. Triglyceride cholesterol
b. Miotic – constriction of pupils of the
c. LDL (Low Density Lipoprotein)
eye
d. Statins
i. Pilocarpine
14. Hypolipidemic
2. Coagulants – Anti-coagulant
a. Decreased lipids
a. Coagulants – for blood clotting
b. Fat soluble (F – Vt ADEK)
b. Anti-coagulant – for anti-blood-
15. Antineoplastics – drugs that replenish
clotting
bodily deficiency
i. Blood thinners, orevents
blood to clot
SOURCES OF DRUGS
3. Emetics – Anti-emetics
a. Emetics – for vomiting
i. Ipecac Syrup • Plants / Animals
b. Anti-emetics – anti-vomiting • Microbes – by products
i. Metoclopramide • Chemical synthesis
4. Diuretics – helps get rid of body salts, • Molecular modification
especially sodium and water. • Biotechnology
a. Classification
i. Loop (furosemide) DRUG DISCOVER IS COMPLEX
ii. Potassium Sparring
(spironolactone)
iii. Osmotic (mannitol) • Pharmacology
• Taxicology

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 PHARM. DOSAGE FORMS PRELIMS
PHARMACEUTICS201 - LEC
AND MEDICAL DEVICES
LECTURE | FIRST SEMESTER

• LADME EARLY RESEARCHES

o Liberation
o Absorption
o Distribution • Karl Wilhelm Scheele
o Metabolism o Lactic acid, citric acid, oxalic acid,
o Excretion tartaric acid, arsenic acid
• Side effects • Friedrich Serturner
• Route of administration o Isolation of morphine from opium
• Dosage form (formulation) • Joseph Caventou and Josep Pelletier
o Physical and chemical compatibility o Isolation of quinine and cinchonine
• Pelletier and Robiquet isolated caffeine
• Robiquet isolated codeine
HERITAGE OF PHARMACY
Even Today…
- The first apothecary
1. Paclitaxel (Taxol)
1. Priest Craft a. From pacific yew tree (Taxus
a. In the Homeric epics baccata)
b. Pharmakon – charm or used to 2. Vincaleukoblastine
drive out evil a. Vinca rosea
3. Digoxin
EARLY DRUGS a. Digitalis lanata

How did they ensure quality of drugs then…

• 16th Century BC
o Papyrus Ebers • Organization of Pharmacopoeias of
§ Named after George Ebers Formularies
§ 800 formulas and 700 drugs o Pharmakon (Drug) Polein (make)
§ Vehicles used before (beer, o USP / NF - First Pharmacopeia
milk, wine, and honey) § Lilitz Pharmacopeia
§ 32 page
NOTABLE CONTRIBUTIONS o Dr. Lyman Spalding
§ Proposed to have national
pharmacopeia
• Hippocrates (460 – 377 BC) § Father of USP
o Father of Medicine
• Discorides (1st Century AD)
o De Materia Medica
• Claudius Galen
o Galen’s Cerate
• Separation of Pharmacy from Medicine
o 1240 AD under Emperor Frederick
II Aereolus Theosphrastus
Bombastus von Hohenheim
§ PARACELSUS (1492 –
1541)

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 PHARM. DOSAGE FORMS PRELIMS
PHARMACEUTICS201 - LEC
AND MEDICAL DEVICES
LECTURE | FIRST SEMESTER

CHAPTER 2: NEW DRUG DEVELOPMENT AND APPROVAL PROCESS

OBJECTIVES: SUMMARY OF DRUG DEVELOPMENT

AND EVALUTION
1. Learn the processes involved in drug
discovery and development
2. Define the phases involved in FDA drug
approval
3. Explain the role of the Food and Drug
Administration (FDA) in the drug
development and approval process.

RESEARCH AND DEVELOPMENT

PROCESS (R&D)

• Development of new drugs is a complex

and costly process
• It takes an average of 12 years and about
$350 million to get a new drug from the
laboratory to the pharmacy shelf.
• R&D involves discovery (preclinical
studies) and development (clinical studies)
• Only one in 1000 compounds which begin
laboratory testing will make it to human
testing NEW DRUG DISCOVER

ROLE OF FDA Agent:

• The Food and Drug Administration (FDA) is
required to review and approve all new
drugs
• The FDA reviews and evaluates new drugs
based on the evidence presented from the
clinical research studies performed by the
drug sponsor typically a pharmaceutical
company.
GAINING APPROVAL TO MARKET
DRUG
Drug Companies
• Must demonstrate that drug is SAFE and
EFFECTIVE for use
• Drug PRODUCTION is controlled and
validated – meet standards
• Biologically characterized
• Preformulation stdies
• Formulation studies
PRE-CLINICAL STUDIES
FILE for IND (Initial Human Testing – Clinical
Studies)
• Phase 1, phase 2, phase 3
FILE for NDA
• Phase 4
1. PRECLINICAL STUDIES
• Synthesis and purification of the new drug
• Pharmacology of the new drug:
o Pharmacokinetics: absorption,
distribution, metabolism, excretion,
half-life
o Pharmacodynamics: mechanism of
action and estimates of therapeutic
effects

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 PHARM. DOSAGE FORMS
AND MEDICAL DEVICES
LECTURE | FIRST SEMESTER
• Efficacy studies on animals
2. IND
• Investigational New Drug (IND):
Application for permission to administer a
new drug to humans
• Outlines the proposal to use the new drug
for human testing in clinical trials
• Studies in humans can only begin after IND
is reviewed and approved by the FDA and
an institutional review board (IRB)
3. CLINICAL STUDIES
• Phase 1: Efficacy studies on healthy
volunteers
• Phase 2: Clinical studies on a limited scale
• Phase 3: Comparative studies on large
number of patients New Drug Application
(NDA) regulatory review
• Phase 4: Continued comparative studies.
Registration and market introduction.
PHASE 1
• Typically involves 20-80 healthy volunteers
(no women of childbearing potential)
• Emphasis is on drug safety
• Goal is to identify major side effects,
metabolism, and routes of excretion
• Lasts about 1 year
• About 70% of drugs will pass this phase
PHASE 2
• Typically involves 100-300 individuals who
have the target disease
• Emphasis is on effectiveness
• Patients receiving the drug are compared
to similar patients receiving a placebo or
another drug
• Lasts about 2 years
• About 33% of drugs will pass this phase
PRELIMS
PHARMACEUTICS201 - LEC
PHASE 3
• Typically involves 1000-3000 patients
• Emphasis is on safety and effectiveness
• Investigates through well-controlled
studies different populations and different
dosages as well as uses new drug in
combination with other drugs
• Lasts about 3 years
• 25-30% of drugs will pass this phase
NDA
• Pre-NDA period: FDA and drug sponsors
meet
• Submission of NDA: Formal step asking
the FDA to consider approving a drug for
marketing
• FDA has 60 days to decide whether it will
file it for approval consideration
• If filed, a review team is assigned to
evaluate the new drug
3 parameters
1. drug product is safe & effective
2. assurance of proper manufacture &
control
3. accurate information on final labeling
FDA ROLE
• The review team evaluates the research on
the safety of the drug and its effectiveness
• The FDA reviews the information to go on
the drug label
• It inspects the facilities where the drug will
be manufactured
• The application will be classified as
“approvable” or “not approvable”
• If approvable, the FDA requests additional
information from the sponsor
• The NDA is again reviewed
• Following drug approval, sponsors of the
drug will be required to continually assess
the safety of the drug
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 PHARM. DOSAGE FORMS PRELIMS
PHARMACEUTICS201 - LEC
AND MEDICAL DEVICES
LECTURE | FIRST SEMESTER

PHASE 4 SOURCES OF NEW DRUG

• Post-market surveillance of the drug to

continually assess the safety of the drug
• May include incidence and severity of rare
adverse reactions, cost-effectiveness
analyses, comparative trials, and quality of
life studies
• Indicate possibly new therapeutic uses for
the drug
• Demonstrate the need for additional
dosage strengths, dosage forms, or routes
of administration
PACKAGE INSERT
• Summary of the entire drug development
process
o Essential chemistry
o Pharmacology
o Toxicology
o Indication and contraindicators
o Adverse effects
o Formulation composition
o Dosage
o Storage requirements
TREATMENT IND
• Sought for orphan drugs targeted for small
number of patients who have rare
conditions or diseases which have no
satisfactory alternative treatments
ANDA
• Abbreviated New Drug Application
o to gain approval to market a
duplicate ( competing
generic ) product that is already
approved and
being marketed by the pioneer or
original sponsor
• Plant materials
• Animals
• Genetic engineering
o Recombinant DNA
o Monoclonal Antibody Production
• Human gene therapy
GOAL DRUG
- A drug perfect in all its aspect
o Produced desired effects
o Most desired route of administration
o Minimal dose
o Optimal activity
o No side effects
o perfect elimination
o Low cost
o Stable
o Elegant
METHODS OF DRUG DISCOVERY
• Careful designed research
• Molecular modification
• Mechanism-based drug design
MOLECULAR IDENTIFICATION
• Chemical alteration of a known and
previously characterized organic
compound for the purpose of:
o Enhancing its specificity for a
particular body target site
o Increasing its potency
o Improving rate & extent of
adsorption
o Modifying time course in the body
o Reducing its toxicity
o Changing the physical or chemical
properties
o Provide desired features

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 PHARM. DOSAGE FORMS PRELIMS
PHARMACEUTICS201 - LEC
AND MEDICAL DEVICES
LECTURE | FIRST SEMESTER

HOW TO ACHIEVE? § Sufficiently stable for the period of

use
• Changes in functional groups, ring
structures or configuration
• Mechanism based drug design
o Beta-blockers
§ dichloroisoproterenol →
promethalol → propranolol
o H2 – antagonists
§ Burinamide → metiamide
→ cimetidine
MECHANISM BASED DRUG DESIGN

• To design a drug that interferes specifically

with the known or suspected
biochemical pathway or mechanism
of a disease process
o Example:
§ Enalaprilat
§ Ranitidine
§ Sertraline
• LEAD compound
o A prototype chemical compound
that has a fundamental desired
biologic or pharmacologic activity
• PRODUGS
o A compound that requires
metabolic biotransformation after
administration to produce the
desired pharmacologically active
compound
• NEW DRUGS
o Any drug that is not recognized as
being safe & effective
EARLY FORMULATION STUDIES
1. Preformulation studies
§ Drug solubility
§ Partition coefficient
§ Dissolution rate
§ Physical form
§ Stability
2. Initial product Formulation and clinical Trial
Materials
§ High pharmaceutical quality
§ Meet analytical specifications for
composition, manufacturing &
control

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 PHARM. DOSAGE FORMS PRELIMS
PHARMACEUTICS201 - LEC
AND MEDICAL DEVICES
LECTURE | FIRST SEMESTER

CHAPTER 3: DRUG DELIVERY SYSTEM

WHAT ARE DRUG DELIVERY o Lower the chance of triggering drug

SYSTEMS? resistance ( broad-spectrum
antibiotics )
• DDS are engineered technologies for the
targeted delivery and/or controlled release Nanotechnology
of therapeutic agents • Nanoparticle method replaces a type of
o Advanced molecular biology gene therapy using viruses
strategies • Glioblastoma (brain cancer)
• Control the release rate and the location in o Nanoparticles target the tumor by
the body where a drug is released delivering an altered gene, or
suicide gene, that is programmed
PHYSIOLOGICAL BARRIERS TO EFFICIENT for cell death
DRUG DELIVERY Using a type of bacteria
• Bacteria deliver drugs to tumors
• Transport in the circulatory system
• Drug movement through cells and tissues
CURRENT RESEARCH ON DDS 3. CARGO

• Categories: Genes, proteins and stem cells

o Routes of delivery
o Delivery vehicles • Using nanovaccines with unique structures
o Cargo and incorporate inorganic material
o Targeting strategy o Vaccine formulated with silica rods
that assemble like a stack of match
1. ROUTES OF DELIVERY sticks
• Nanovaccine that combines a bacterial
Traditional Routes of delivery DNA (programmed to trigger an immune
response) and a nano-sized inorganic
• Oral (swallowing) substance
• Inhalation o Injection of the nanovaccine forms
• Topical (through the skin) complexes
• Injection
4. TARGETING STRATEGIES
New Method of Delivery
• Microneedle arrays (through the skin) Reverse-engineering approach
o Penetrate the skin but don’t reach
• A plant virus nanoparticle that can target
the nerves in the skin – painless
medication delivery and attach itself to prostate cancer cells
o Viral nanoparticles do not need to
o Vaccine delivery
be modified to behave in desired
2. DELIVERY VEHICLES ways, and their actions within the
human body are well understood
Biotechnology o Plant-based nanoparticles are
biodegradable, harmless to
• Improved medications that can target humans, easy to use and cheap to
diseases more effectively and precisely produce

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 PHARM. DOSAGE FORMS PRELIMS
PHARMACEUTICS201 - LEC
AND MEDICAL DEVICES
LECTURE | FIRST SEMESTER

NEW CONCEPTS IN PHARMACOLOGY 3. Drug discovery and development and as an

THAT INFLUENCE DESIGN OF DDS aid to planning clinical trials

Concepts: PHARMACOGENOMICS

1. Pharmacogenetics • Carries on that tradition by applying the

2. Pharmacogenomics large-scale systemic approaches of
3. Pharmacometabolomics genomics to understand the basic
4. Chronopharmacology mechanisms and apply them to drug
discovery and development
• Examine the way drugs act on the cells as
PHARMACOGENETICS revealed by the gene expression patterns
and thus bridges the fields of medicinal
Pregenomic era: chemistry and genomics
• Promises to enable the development of
• The study of influence of genetic factors on safer and more effective drugs
action of drugs as opposed to genetic • Will ensure that the right drug is given to
causes of disease the right person from the start
o To determine which drug regimen
Now:
best fits their genetic make-up
• The study of the linkage between the
PHARMACOMETABOLOMICS
individual’s genotype and the individual’s
ability to metabolize a foreign compound
o The pharmacological effect of a • Pharmacometabonomics
drug depends on • Is a field which stems from metabolomics,
pharmacodynamics and the quantification and analysis of
pharmacokinetics metabolites produced by the body. It helps
• Covers the influence of various factors on in studying drug effects and variation in
the 2 processes drug response.
• The application of metabolomics for the
Drug Metabolism study of drug effects and variation in drug
response
• One major determinant of drug clearance
• The direct measurement of metabolites in
• Factor responsible for interindividual
an individual's bodily fluids, in order to
differences in pharmacokinetics
predict or evaluate the metabolism of
Genetics pharmaceutical compounds
• A discipline that will contribute to
• Account for 20 – 95% of variability in drug personalized drug therapy
disposition and effects
• Genes influence pharmacodynamics and CHRONOPHARMACOLOGY
pharmacokinetics
• Genetic polymorphisms • Variations in the effect of drugs according
to the time of their administration during the
Role of pharmacogenetics in the
day
pharmaceutical industry:
o Circadian rhythms
1. For study of the drug metabolism and § The rhythms of disease and
pharmacological effects pharmacology can be taken
2. For predicting genetically determined into account to modulate
adverse reactions

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 PHARM. DOSAGE FORMS PRELIMS
PHARMACEUTICS201 - LEC
AND MEDICAL DEVICES
LECTURE | FIRST SEMESTER

treatment over the 24-h

period
CHARACTERISTICS OF AN IDEAL DDS
1. It should increase the bioavailability of the
drug
2. It should provide for controlled drug delivery
3. It should transport the drug intact to the site
of action while avoiding the non-diseased
host tissues
4. The product should be stable and delivery
should be maintained under various
physiological variables
5. A high degree of drug dispersion
6. The same method should be applicable to a
wide range of drugs
7. It should be easy to administer to the
patients
8. It should be safe and reliable
9. It should be cost-effective