Knipp 1 Flashcards
drug performance 1
ability of drug to elicit therapeutic response
pharmacokinetics: how body responds to drugs
pharmacodynamics: therapuetic response
global formulation
to transfer therapeutic compound, it requires a reproducible dosage form.
same drug each each batch
ADME
absorption, distribution, metabolism, excretion
drugability
discovery stage, ability of NCEs to bind to drug target, in vivo models are assessed
druggable protein: proteins that can bind drug like compounds with high affinity and candidates that perform best advance
developability
drug product performance, evaluating properties that allow proper therapeutic response. pharamcokinetics and pharmacodynamics determine safe and efficacious use
**drug formulation design
physicochemical properties of the drug, physicochemical properties and composition of the formulation, biological factors that influence performance (ADME and toxicity)
drug performance
ability of drug to elicit therapeutic response, safe therapeutic range, lack of toxic/non efficacious response, described by pharmacokinetics and pharmacodynamics, function of drug and formulation
physicochemical properties that affect absorption
solubility, stability in solution, molecular size & shape, pka, lipophilicity, physical state (amorphous or crystalline)
solubility
depends on molecular structure, physical state, composition of solvents, measurement methods
partitioning coefficient
ratio of concentrations of two immiscible solvents
pH partition hypothesis
for drugs absorbed by passive transcellular mechansim, permeability transport depends on the fraction of unionized drug at intestinal pH
extra+intracellular pH effects drug transport
organelle pH can result in the trapping of a molecule in a cell
**overcoming effects of pH partition hypothesis
functionalize compound-change pka,
prodrug strategy (modify moeity and molecule to be recognize by transporter),
salt selection (ion pairing effective, salt form can alter unionized fraction)
drug delivery system
formulation factors affecting absorption
dosage form design
rates of drug release from the dosage form
residence time at absorption site
excipients
not inert, but pharmacologically inert, inactive therapeutic
common excipients
cellulose, sugars, starch, synthetic, inorganic, magnesium
factors for excipient selection
origin, quality and purity, stability, cost, toxicological considerations
**ingredients affecting bioavailability, stability, marketing considerations
disintegrates enhance rate of disintegration/dissolution
coatings-control release
flavors/sweeteners mask drug taste
colors-recognition
miscellaneous ingredients
common methods for excipient compatibility testing
mechanical stress
tablets processed by wet granulation
using amorphous drug
suspension or solution of excipients
**organoleptic senses to consider when coating/blinding clinical trials
sight, smell, sound, taste, touch
solid dosage form requirements
must have content uniformity (each tablet has approx 85%-115% API, or tighter control)
have good organoleptic properties
need to be stable for 2 year shelf life
reproducible release metrics as measured by dissolution for batch release
must not be friable (does not break)
