L7 - physiochemical properties of small drugs
No description yet. This curated deck is ready for daily study.
Card preview (24)
the body can’t absorb solids, so what must happen to a drug to have its biological effect?
• must be released from its dosage form at the site of administration • undergo dissolution
what can liberation (release of drug from dosage form) cause?
can affect drugs bioavailability (quantity of drug that reaches site of action + rate at which drug get there)
what is bioavailability influenced by?
• dosage form (+ excipients & manufacture method) • physiology of site of administration
steps of release of oral dosage form (tablet with insoluble permeable coating)
the drug dissolves inside the tablet (osmotic pump)
steps of release of oral dosage form (coated tablets)
• dissolution of coating • it then disintegrates • disaggregation (fine granules/ primary particles) • go into solution
steps of release of oral dosage form (drug suspensions)
• particles of drug suspended in liquid • don’t have to released from dosage form • can just diffuse to epithelium
how does drug dissolution occur from crystal to liquid?
• salvation of drug molecules at crystal surface makes a STAGNANT layer of drug solution • this is the diffusion layer • drug molecules will diffuse across the diffusion layer into the bulk dissolution medium • this can be the contents of the GI tract
what is the rate of dissolution dependent on?
the slowest step out of salvation of drug molecules at crystal surface and diffusion across diffusion layer
what can dissolution at a constant temperature and pressure be described as?
Noyes-whitney equation
notes-whitney equation
dm/dt = D A (Cs - C) / h
dm/dt
dissolution rate of drug (kg s-1)
D
diffusion coefficient of solute in dissolution medium (m s-1)
A
surface area of drug particle (m2) (part in the middle inside the diffusion layer)
Cs
solubility of the drug (kg m-3)
C
concentration of drug in bulk solution at time (kg m-3)
h
thickness of the boundary layer (diffusion layer) (m)
generally C () CS
C «_space;Cs conc of drug in bulk sol is usually a lot smaller than the solubility of the drug
key parameters that affect the rate of dissolution of a drug
• surface area of particles (particle size + wettability) • molecular weight • solubility (hydro and liphphilicity, crystal structure) • GI tract (viscosity, volume of liquid, movement, secretions, pH)
brief overview o
• drug diffuses from site of release to epithelium • across epithelium • drug in sol passes mucus layer on epithelium • through apical layer, through cell, through basolateral layer • into systematic circulation
transcellular pathway (major)
across (through) the cells into the blood
paracellular pathway (minor)
alongside the cell (between cells) to the bloodstream
what makes paracellular pathway difficult?
• tight junctions between neighbouring cells • adherens junctions which join cytoskeleton of cells together • desmosomes where proteins cross gap between cells rate limiting junction
what drugs can be absorbed across paracellular pathway?
small hydrophilic (due to aqueous medium in between the cells) drugs can pass between cells but rate of diffusion is affected by tight junctions
3 main ways that drugs go through transcellular pathway
• passive diffusion: solutes diffuse into cells down a conc gradient and go through lipid bilayer and then cytoplasm • facilitated diffusion (selective) - down a conc gradient - uses transporter/carrier protein • active transport - against a concentration gradient - needs energy - carrier mediated transport