TOPIC 2 Flashcards
MOLECULAR DISCOVERY &
CHARACTERIZATION
- GOAL DRUG
- PRODRUG
- BIOASSSAY
- LEAD COMPOUND
identified during drug
discovery and
development
It serves as the
starting point.
chosen based on their
ability to interact with
a specific target
Lead Compound
the ultimate
objective in drug
development,
which is to create a
safe and effective
medication
Goal Drug
an inactive or less
active precursor
molecule of a drug
that undergoes a
chemical or
enzymatic
transformation
within the body to
become an active
therapeutic agent
Prodrug
A compound that requires
metabolic biotransformation
after administration to
produce the desired pharmacologically active compound
Prodrugs
Aspirin is a prodrug of?
Salicylic acid
Enalapril ->
enalaprilat
Epinephrine ->
Dipivefrin
Epinephrine -> Dipivefrin:
◦ Enhanced solubility
◦ Enhanced lipophilic character
◦ Enhanced duration of action
Reserpine
▫ Rauwolfia serpentina
▫ (reserpine) tranquilizer and hypotensive
agent
Periwinkle
▫ Vinca rosea
▫ Vinblastin and Vincristine
▫ For cancer
Pacific Yew Tree
Taxus brevifolia
Animal Source
Endocrine glands of cattle, sheep and swine
Pregnant mares.
Embryo
Endocrine glands of cattle, sheep and swine
Thyroid extract, insulin and pituitary hormone
(replacement therapy)
Pregnant mares
Source of estrogens
Embryo
vaccines
Microbiological Source
penicillin, cephalosphorin,
tetracyclines,
aminoglycosides, lovastatin
Genetic engineering
Recombinant DNA
Monoclonal Antibody production
PRE- CLINICAL TRIAL:
●Chemical and physical characterization
●Pharmacology
●Pharmacokinetics
●Pharmacodynamics
●Analytical studies
●Toxicology
●Pharmaceutics
●File IND Application
Once passed
with pre clinical
submit
INVESTIGATIONAL
NEW DRUG (IND)
the science of the properties of the drugs
and its effects in the body
Pharmacology
the study of the interaction of drugs
with cells
Pharmacodynamics
the handling of a drug within the
body, it includes the ADME processes
Pharmacokinetics
are observational studies that are aimed
at objective examination and assessment − analysis − of
causal relationships between exposure to potential disease
determinants (risk factors) and subsequent disease
Analytical studies
the study of the A/E of the chemical agents on living
organisms
Toxicology
the general area of study concerned with the
formulation, manufacturing stability and effectiveness of a
pharmaceutical dosage form
Pharmaceutics
an exclusive rights to the use and profits of a novel
pharmaceutical for a limited term
Patent the drug
PRE- CLINICAL TRIAL Special consideration is given on
Orphan drugs and
Treatment IND, Emergency IND
Physical – Chemical
Characterization:
- Solubility
- Partition coefficient
- Dissolution rate
- Physical form
- Stability
preclinical data to check whether the product is safe for initial testing in humans
Animal Pharmacology and Toxicology Studies
information about composition, manufacturer, stability, and controls used for manufacturing the drug substance and the drug product
manufacturing information
detailed plan for proposed clinical studies to assess whether the initial phase trials will expose subjects to unnecessary risks
clinical protocols and investigator information
schedule of dosage
Dosage Regimen
the amount that may be expected to
produce, in adults, the medicinal effect for which it is
intended
Usual dose
amounts of drug that may be
prescribed within the work of usual medical practice
Usual dosage range
dose administered to children
Pediatric dose
also the priming or loading dose, is the
amount required to attain the desired concentration
of the drug in the blood or tissues
Initial dose
the amount administered to a patient before
exposure or contraction of the illness
Prophylactic dose
the amount which is administered to a patient
after the exposure or contraction of an illness
Therapeutic dose
The relationship between the desired and undesired effects of
a drug
Therapeutic Index
Therapeutic Index:
TD50/ ED50
Factors Affecting the Dose
Age
Pharmacogenetics– genetic polymorphism
Body Weight
Body Surface Area - nomogram
Sex
Pathologic State
Tolerance
Concomitant Drug therapy
Time and conditions of administration
Dosage Form and Route of Administration
Phase I:
Tolerance and safety
20 – 100 healthy volunteer
Toxicological studies
Phase II
100 – 300 first controlled studies
on patients
Efficacy and therapeutic index
Phase III
1000 – 3000 extended clinical trials
dose, efficacy, toxicity and
side effects
Performed with the final dosage form
developed in phase II
Side effects are monitored
Phase IV
Post marketing studies
Drug product may be improved
Modification on drug formulation as
obtained from manufacturing scale
up
and validation process may be done
Additional clinical studies
NDA is submitted to the FDA for _____
showing product is effective by all parameters
review and approval
The data gathered during the animal studies and human clinical
trials of an ______ become part of the NDA.
Investigational New Drug (IND)
increase in the batch size from
the clinical batch, submission batch, or to
the full-scale production batch size, using
the finished, marketed product.
Scaleup
USP–NF <795>
Pharmaceutical Compounding- Nonsterile
Preparations
USP–NF <797>
Pharmaceutical Compounding- Sterile
Preparations
USP–NF <1160>
Pharmaceutical Calculations in Prescription
Compounding
USP-NF <1163>
Quality Assurance in Pharmaceutical
Compounding
USP-NF <1176>
Prescription Balances and Volumetric
Apparatus
USP-NF <85>
Bacterial Endotoxins Test
USP-NF <1151>
Pharmaceutical dosage form
USP-NF <795>
Pharmacy Compounding- Nonsterile
Preparations
USP-NF <797>
Pharmacy Compounding- Sterile Preparations
USP-NF <800>
Hazardous Drugs
is “that which holds the
article and is or may be in direct
contact with the article.”
Container
is “that which is in direct contact
with the article at all times. The
closure is part of the container.
Immediate container
It protects the contents from extraneous solids
and from loss of the article under ordinary conditions of
handling, shipment, storage, and distribution.
Well-closed container
protects the contents from contamination by extraneous liquids,
solids, or vapors; from loss of the article; and from
efflorescence, deliquescence, or evaporation
under the ordinary or customary conditions of handling, shipment,
storage, and distribution and is capable of tight reclosure
Tight container
impervious to air
or any other gas under
the ordinary or
customary conditions of
handling, shipment,
storage, and
distribution.”
Hermetic container
and Sterile hermetic
Other containers:
Multiple-unit containers and
Multiple-dose container
Single dose container Single-unit
package
Plastic containers advantages
Lightness of weight
Versatility
Convenience
For unit
dose delivery
movement of the
product components outward
toward the container
Permeability
movement of the
components of the container into
the contents
Leaching
binding of molecules to
polymer materials
Sorption
deformation which may be
softening, hardening and other
physical changes in the plastic
container
Alteration of container
A test used to determine resistance to water
attack
Amount of alkali that release into the the content
LEACHING
is used to
reduce the risk of poisoning in children via
the ingestion of potentially hazardous
items including certain prescription and
over-the-counter (OTC) medications,
pesticides, and household chemicals.
Child-resistant (C-R) packaging
one that is significantly difficult to open
by children 5 years under
Child-resistant (C-R) packaging
Child-resistant (C-R) packaging 4 Basic
designs:
- align the arrows
- press down and turn
- squeeze and turn
- latch top
Cold:
between 2°C and 8°C
**not more than 8°C
freezer
− 25°C and − 10°C ( ** some below 20c)
Cool:
8°C and 15°C
Room temperature:
Ambiance temperature” Temperature prevailing in a
working area.
Controlled room
temperature
20°C to 25°C but also allows for temperature variations
between 15°C and 30°C
The mean kinetic temp (MKT) should not exceed 25c
Warm:
30°C and 40°C
Excessive heat:
Above 40°C
Protection from light
Light-resistant container
Protection for freezing
Protect the product from Freezing
