Drug discovery + extraction and sample prep Flashcards
What are the processes used to extract drugs from natural sources?
infusion, decoction, maceration, percolation, continuous hot extraction & counter current
Describe the process of infusion
drug stood in hot or cold water for a short time / solid
Describe the process of decoction
extraction of soluble constituents by simmering in boiling water for specified time / solid material should be hard and conc not adjusted / thermal degradation
Describe the process of maceration
prolonged infusion in aq alcohol in a closed container
Describe the process of percolation
maceration then flow of fresh solvent passing over ground material at a specified time
What is continuous hot extraction?
uses a soxhlet extractor also called continuous hot percolation , drug extracted using hot solvent
What is counter current?
multiple liquid-liquid extractions
What does Galenical mean?
medicinal extract or tincture derived from natural sources
What does Menstruum mean?
solvent used in extraction
What does marc mean?
insoluble materials remaining after extraction
What are the types of purification methods available?
SPE/sPME (solid phase) / filtration (solid phase) / chromatography (solid phase) / Separating funnel (immiscible liquid phases) / counter current distribution (immiscible liquid phases) / crystallization (miscible liquid phases) / fractional distillation (miscible liquid phases)
What do acid base extractions require?
pH change of aq phase
What are the methods used to separate drugs from miscible phases?
rotary evaporation (vacuum & heat) / fractional distillation / fractional crystallization (based on solubility) / sublimation/ lyophilisation (freeze drying, solid to gas using lyophiliser)
What are the key stages of a drug discovery project?
target identification / hit or lead identification / lead optimisation / pre-clinical development / clinical development phase 1,2,3
What is a hit?
a compound with biological activity in a basic model
What is a lead?
a compound with biological activity in in vitro models
What is a candidate?
a compound with an overall profile consistent with target product profile
What is LogD and how is it calculated?
same as LogP apparent / D = conc of drug in Octanol/conc in water / should always be quoted with pH 7.4
What is LogP?
a measure of lipophillicity in a compound, its partition coefficient between and organic and an aq solvent. P = conc of drug in Octanol/ conc of unionised drug in water
What’s significant about the logD value of neutral drugs?
It’s the same as its logP value
For ionisable drugs how does their logD value relate to logP?
LogD is less than or equal to logP
What does an increase in logD result in and why is it important?
it will cause an increase in potency and permeability / decrease in solubility ,metabolism, protein bonding and toxicity therefore its ability to affect other factors makes it important
