Dose Form Design EXAM 1
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Dose Form Design EXAM 1
DOSE FORM EXAM1 drug development prodrug lead compound INDA FDA NDA IRB NDC
Dose form design exam 1
Name 3 discovery methods for new drug development
1) Random / Accidental
2) Targeted Screening
3) Molc. modification / mechanism-based
Name the 4 main sources for new drug development
4) Genetic engineering
What is a common botanical source for drug development?
Name 3 classes for drugs obtained from animal sources
Name a downside to an animal-derived drug
May cause an immunoresponse
Give 3 examples of genetic engineering
1) recombinant DNA (rDNA)
2) monoclonal antibody therapy (MoAb)
3) gene therapy
Define "goal drug"
the ideal drug with full theraputic efficacy and no side effects
Define "lead compound"
prototype compound with fundamental desired pharmacologic / biologic activity that may or may not be modified to improve desired function / features
an inactive substance requiring
to become pharmacologically active
What are the benefits of a prodrug?
Prodrugs can be designed for better solubility, absorption, biostability, and/or prolonged release
What is a common way to achieve an ER or SR medication?
Combine a drug with it's prodrug...the active drug is released immediately and the prodrug is metabolized and released later for an extended effect
What are some obstacles to new drug development?
-complex / time consuming process
-work must be conducted over different fields
-disease process must be researched
-large $ investment
Explain the difference between Proprietary and Nonproprietary drug names.
: patented trademark or brand name given to manufacurers
: generic name given by USAN council specifically for each compound
Explain the difference between an empirical and systematic name.
: # of atoms and their relationships / ratios (ex: C
: descriptive name with relative locations of each atom (ex: 2-chloroethyl p-amino acid)
How does the FDA define a "new drug"?
-any new chemical entitiy
-a new use for an established drug
-a new dosage schedule / regimen
-a new route of admin.
-a new dosage form
-change in drug's formulation / manufacturing
-new combo of existing drugs
What does the first group of #'s in the NDC stand for?
Manufacturer ("Labeler Code")
What does the second group of #'s in the NDC stand for?
Drug Formulation ("Product Code")
What does the third group of #'s in the NDC stand for?
Package size and type ("Package Code")
What are the 5 steps of the new drug approval process?
1) Biologic characterization of the drug
2) Formulation studies
5) Post-market surveillance
What is the approximate timeline for the investigational research steps of a new drug?
-review of data
-review of data
Why are animal studies conducted?
To establish safe dosage range and toxic side effects. If too toxic, no human trials
Explain the basic INDA process
Sponsor proposes protocol and requests permission of FDA to test on humans. FDA has at least 30 days to evaluate data of drug and data from animal studies before approving / denying.
What are some requirements for the INDA?
-sound statistical methods
-suitable basis for choosing test subjects
-safeguards to protect subjects
What must be included in the sponsor's protocol?
-kinds of patients to be studied
-conditions / parameters to be measured
-how data will be collected / reported
What is a Clinical Investigator and what must they provide in order to participate in a trial?
Clinical Investigator is the "middle-man" between the sponsor and the Institutional Review Board who conducts trials on human subjects.
Must provide - statement of education, scientific training, experience, and signed statement of ethics
What must the informed consent form inform subjects of?
-purpose and duration of the study
-risks / discomforts
-alternative options / procedures
-MUST be in subject's native language and in simple terms
What is the Institutional Review Board (IRB)?
-"Ethics Committee" responsible to review and monitor biomedical research
-has purview over hospitals, universities, clinics, etc
-composed of docs, scientists and is ethnically diverse
-is non-governmental / non-regulatory
What are some criteria for approving research?
-risk to subjects are minimized
-risks are "reasonable" in relation to benefits
-selection of subjects is equitable
-informed consent is documented
-all data is monitored
When can foreign studies be used?
When they are well designed and well conducted by qualified investigators using applied ethical principles
What are some inportant aspects of clinical trials?
-controlled for age, gender, disease state, etc
-must be double-blind ; placebo controlled
What is the purpose of phase I clinical trials?
-study how drug is absorbed, processed, and excreted in
-effects on organs / tissues (healthy --> diseased?)
-initail discovery of side effects
-how much drug should be taken and how often
How many drugs pass from phase I to phase II?
13 to 14 out of 20 (~67%)
What is the purpose of phase II clinical trials?
in treating people
with the disease
-get clearer picture of side effects and risks
How many drugs pass from phase II to phase III?
5 to 6 out of 20 (~25%)
What is the purpose of phase III clinical trials?
determines drug effectiveness in up to several thousand patients with the disease at different levels
try to have a more diverse population and longer term of study (3-6 years)
find optimum dosage and less common side effects
When are some drugs "fast-tracked" through the approval process?
When a disease has no current known cure
Drugs with strong evidence for a disease of high leathality (ex:AIDS)
What 6 things must be included in the New Drug Application?
composition, toxicology, drug behavior in body, testing results, manufacturing process, labeling
What occurs during the FDA review of a NDA?
inspection of machinery and facilities, review of data, final approval by Advisory Committee
What is Post Market Surveillance?
ongoing perpetual monitoring of unexpected side effects in order to change drug labels or provide new warnings
"phase IV" clinical trials
What are the pharmaceutics concerning a drug?
formulation, manufacturing, stability, effectiveness
What is the "master formula" of a drug?
The initial formulation that gets scaled-up for mass production (handmade-->machine)
Define the term comminution
reduction of particle size via mortar and pestle
Define the term trituration
the use of a mortar and pestle
Describe how particle size can affect a drug
affects formulation and efficacy
smaller particles are better absorbed due to incr. surface area
What is polymorphism and why is it important?
crystalline vs amorphous forms
crystals dissolve more slowly and amorphous forms dissolve more quickly
Why do all drugs need some degree of aqueous solubility?
therapeutic effect - the body is an aqueous system
What are the advantages / disadvantages to salt vs ester forms?
esters are more pleasant smelling / tasting
salts have better solubility
How does pH / pKa affect a drug?
can determine the drugs solubility in water and where it is absorbed in the body (acidic stomach vs basic intestines)
What is a co-solvent?
a solvent to help increase the solubility of a poorly water-soluble substance
ethanol, glycerin and PEGs often used
What is complexation?
a drug is complexed with something to protect it from being destroyed in water
What is the partiton coefficient of a drug?
the lipid/water solubility
how the drug dissolves into organic and inorganic solvents and suggests how the drug will work in the body
What are the 5 destructive processes to drug stability discussed in class?
hydrolysis - interaction with water
oxidation - interaction with oxygen
polymerization - interaction with other chemicals
decarboxylation - removal of carboxyl group
deamination - removal of amine group