L7 - Physicochemical properties of small drugs

• Release/Liberation(What is it? What is it influenced by?)

  Manner in which a drug is made available for absorptioninfluenced by: site of administration, dosage form, excipients
• Bioavailability(What is it? What is it affected by?)

  Extent and rate at which a drug reaches circulation. How available drug is to the body- Affected by lipophilicity/molecule size
• Dissolution


  A solid drug dissolving in a liquid

  
• Disintegration


  Breaking apart of a dosage form into smaller particles. (SA increases)
• Disaggregation


  Separation of aggregated particles into individual particles
• Aqueous suspension(what is it? Why is release fastest from this form? What about effervescent tablets?)

  - Drug particles dispersed in a liquid medium- Release from aqueous suspension is fastest as there's no dissolution step- For effervescnet tablets, dissolution occurs prior to ingestion
• Drug release from gastro resistant tablets(What are they? Where does disintegration begin? What does this mean for drug release?)

  Tablets with a coating that is stable in the stomach. pH sensitive.- disintegration only begins in small intestine- drug release is delayed, rate at which drug is available is reduced.
• Dissolution process(What is it? What are the two main steps?)

  Rate at which drug particles dissolve in solution. - Solvation at crystal surface to create saturated layer- Diffusion of dissolved molecules across this layer into bulk solution
• Noyes-Whitney equation(What does it describe? What is it?)

  Describes dissolution rate at a constant temperature.dissolution rate = DS/h x (Cs-Cb)where D = diffusivity of drug in solutionS = particle SAh = thickness of diffusion layerCs = solubility of drugCb = conc of bulk solution

  
• Dissolution rate(What is it? How can we increase rate?_

  how many molecules dissolve per unit time- increase by making smaller particles to increase SA
• Solubility

  Maximum amount of drug that can dissolve in a solvent

  
• Diffusivity


  How easily a drug diffuses in a solution
• Thickness of diffusion layer


  Distance between the stagnant layer and bulk solution

  
• Bulk solution


  Solution outside the diffusion layer
• Cbulk


  Concentration of drug in the bulk solution
• Flow


  Movement of molecules in a system- The further a system from equilibrium, the faster it moves towards equilibrium
• Flux(What is it? What's the equation? What's its relationship to energy gradient?)

  Rate of flow of moleculesJ = cvwhere J = flux (mol/sec/cm^2)c = conc. of molecules in motion (mol/cm^3)v = velocity (cm/sec)Flux is directly proportional to energy gradient
• Release vs membrane transport

  Release - drug dissolves at administration siteAbsorption - drug crosses membrane to reach blood
• Extravascular


  All administration methods except IV
• Diffusion - Fick's 1st law


  Relationship between flow and concentration gradient.Substances flow from higher conc to lower conc.
• Stokes-Einstein equation(What does it do?)

  Relates diffusivity to environmental conditions

  
• Diffusivity(How is it affected by molecular volume, solvent viscosity and temp?)

  - decreases with increasing molecular volume- decreases with increasing solvent viscosity- increases with increasing temp
• Fick's First Law equation(What's the equation? How does flux relate to SA and membrane thickness?)

  J = ADk/Δx x (C1 - C2)where J = fluxA = SA of moleculek = partitiion coefficientΔx = membrane thickness(C1-C2) = concentration difference across membrane- Flux is directly proportional to SA, and inversely proportional to membrane thickness
• Diffusion coefficient


  Measure of how easily a molecule diffuses in a medium
• Partition coefficient


  Measure of a drug's distribution between two phases (eg oil and water)A ratio of drug solubility in two phasesk = Coil / Cwater