DOSAGE I: Exam 1 Flashcards
Who are the subjects of preclinical trials?
Animals
Who are the subjects of clinical trials?
Humans
What are the cardinal rules of dosage forms?
- Know what you have
- Make the same thing every time
(controlled by specifications -> binding quality standards)
What are the universal tests for New Drug Products?
- Description (only physical test -> appearance of drug)
- Identification (HPLC)
- Assay (test of potency/strength)
- Impurities
What are the challenges to drug discovery/design?
- Short time line
- Broad dose range (can’t be too close to fatal range)
- Minimal amounts of API
- API with different attributes
What is an abbreviated new drug application (NDA) used for?
Generic drugs
What is a biologics license application used for?
Vaccines + monoclonal antibodies
What is ADMET?
A = Absorption
D = Distribution
M = Metabolism
E = Excretion
T = Toxicity
What are the pre-formulation studies/tests?
- drug solubility
- partition coefficient
-> how much of the drug gets absorbed - dissolution rate
- physical form
- stability
What happens during Phase I of clinical trials?
Determine human pharmacology of the drug structure:
-activity relationships
-side effects with increasing doses
-evidence of effectiveness
What happens during Phase II of clinical trials?
- dose selection
- studies for effectiveness in patients with the condition
What happens during Phase III of clinical trials?
Hundreds to thousands of patients in controlled and uncontrolled trials
Volume/Part in Code of Federal Regulations (CFR) of General Provisions
Volume 21, Part 211
When was the NECC FDA inspection?
October 2nd, 2012
What did the FDA find in the 2012 NECC inspection?
- 83/321 vials contained a greenish-black foreign matter
- tarnished discoloration on surfaces of autoclave
- airborne particles from recycling facility only 100ft away from NECC
Define “reproducibility” in terms of drug design
- each dosage form contains between the same amount of drug
- drug has the same performance in the body
What is Cmax?
Max concentration of drug in plasma / how much is in the system
What is Tmax?
How much time it took to reach Cmax
What comprises the disposition phase (relating to ADME)?
Distribution, Metabolism, Excretion
What are the Factors Governing Drug Performance in the Clinic?
- Physicochemical properties of the API (i.e. solubility)
- Physicochemical properties and the composition of the formulation
- Physiological barriers that influence the targeted bioavailability of the drug
What are excipients?
An PHARMACOLOGICALLY inert (but otherwise active) substance that forms a vehicle for a drug
What are some common excipients?
- Cellulose based
- Sugars (i.e. sucrose, mannitol)
- Starch
- Synthetic polymers
- Magnesium stearate
Poor absorption or permeation is likely when (Lipinski’s rules):
- More than 5 H-bond donors
- More than 10 H-bond acceptors
- MW > 500
- MlogP > 4.15
- ClogP > 5
What is the Partition Coefficient?
Ratio of concentrations in two immiscible solvents (i.e. octanol and water)
Define “druggable protein”
Proteins that can bind drug-like compounds with binding affinity below 10 mM (inferred that compound can functionally modulate the protein)
