Knipp's Lecture Flashcards
Drug Product Performance
- ability of a drug to elicit a therapeutic response
- ability of drug to stay in a safe range during dosing regimen
- lack a toxic response
Goal of Formulations
- take a new therapeutic compound and develop a reproducible dosage form
- dosage form will go through different stages and altercations
Reproducibility of Drug
- each dosage form containing same amount of drug
- same performance in the body
ADME
Absorption (into bloodstream or GI tract)
Distribution (separated or divided)
Metabolism (made into a metabolite)
Excretion
Normally measured levels in the arm
Absorption vs Disposition Phase
Absorption begins to decline as the disposition phase begins to increase
Absorption Rate
defined by the properties of the drug, drug composition and formulation, and physiological barrier between circulation and GI tract
Druggability
- discovery stage
- assess the ability of the API to bind to a drug target (below 10mM)
- extensive characterization to demonstrate potential efficacy to perform like a drug
Process of Drugability
Gene: drugable genes are identified by methods
Protein: genes that encode disease-related proteins are identified
Pharmacophore: genes are converted to proteins and find binding cavities
Developability
- evaluating properties that will be used to generate a formulation capable of ensuring compound can be therapeutic
- begins to look at solubility and dissolution rates
- ADME
Drug Formulation Design
- Physiochemical properties of drug
- Physiochemical properties and composition of formulation
- Biological factors that influence performance (ADME & Toxicology)
Physiochemical Properties of Drug that Affect Absorption
Solubility
Stability
Lipophilicity
Size and Shape
pka
Physical State
Solubility Depends on…
Molecular Structure
Physical State
Composition and Types of Solvents
Measurement Methods
How to overcome effects of pH Partitiion Hypothesis
- Change pka
- Prodrug Strategy (modifications of charges and molecule)
- Salt Selection (ion pairing)
- Drug Delivery System
Formulation Factors Affecting Absorption
Dosage Form Size (size, compositions, shape)
Rates of Drug Release (slower or faster)
Residence Time (mucoadhesives and coatings)
Excipients
substances added to therapeutically active compounds to improve appearance, bioavailability, stability, and palatability
pharmacologically inert
