molecules vs materials

• what is a molecule?

  a group of two or more atoms that form the smallest identifiable unit into which a pure substance an be divided and still retain the composition and chemical properties of that substance.
• what is a material?

  a substance (single) or mixture of substances that constitutes an object. Materials can be pure or impure, living or non-living matter.
• name attractive forces between molecules...

  1. ion-ion
  2. ion-dipole
  3. dipole-dipole
  4. h-bond (type of dipole-dipole)
  5. hydrophobic interactions
• describe a dipole-dipole interaction...

  Interaction between an area of electron density created by unequal sharing of electrons in a covalent bond and an area of electron deficiency in an adjacent molecule
• give examples of intrinsic properties...

  solubility, melting point, enthalpy of fusion, pKa, log P, intrinsic dissolution rate, hygroscopicity, stability
• give examples of derived properties (material properties)...

  particle shape, morphology, habit, density, powder flow, compressibility, rugosity, physical form (crystalline, amorphous) and excipient compatibility
• what do intrinsic properties depend on?

  the molecular structure
• what do derived properties depend on?

  on the interaction among these molecules within the material
• what do materials consist of?

  a group oof molecules interacting through intermolecular forces
• what form are drugs absorbed in?

  absorbed as individual molecules - their absorption of its related to their physicochemical properties
• why is aqueous solubility important?

  • biological fluids are aqueous in nature
  • the relevant solubility is the highest concentration a drug can achieve in the biological fluid
  • the bioavailability of a drug is determined by its solubility, which directly influences the dissolution rate. For poorly soluble drugs, this can be the rate-limiting step in absorption.
• Dissolution of a solid in a liquid is composed of two consecutive stages, what is stage 1?

  • an interfacial reaction that results in the liberation of solute molecules from the solid phase into the liquid phase
  • involves a phase change so that molecules of the solid become molecules of the solute in the solvent in which the crystal is dissolving
• Dissolution of a solid in a liquid is composed of two consecutive stages, what is stage 2?

  solute molecules migrate through the boundary layer surrounding the crystal to the bulk of solution
• how does the melting point impact solubility?

  • Each 100ºC increase in mpt above 25ºC (rtp) corresponds to at least a 10-fold decrease in solubility)
  • Lower melting point, more likely to be soluble - because higher mpt = more energy to break intermolecular bonds
• what is the solubility and dissolution rates of a weak acid and base dependant on?

  the pH of the biological fluid they encounter upon administration
• what pH do acidic drugs exhibit a higher permeability at?

  pH of 6.5 or lower - drug is less ionised
• what pH do basic drugs exhibit a higher permeability at?

  pH 7.4 and above - drug less ionised
• some dosage forms may ‘provide’ a higher pH to enhance diffusion across the membrane for a basic drug 
• what is a barrier to absorption - in relation to pKa?

  in the stomach where pH is very low, the concentration of unionised acidic drugs is very high - however very little drug absorption across the stomach wall occurs due to its thick muscular walls and low surface areas
• what is the pH range of the GI tract?

  1.2-6.8
• what can the log P predict?

  drug permeability via passive diffusion
• what form do ionisable compounds penetrate membranes?

  the unionised form
• drug absorption is a balance between what?

  Aqueous solubility and membrane permeability - for a drug to be absorbed, it must exhibit sufficient water solubility to be dissolved in body fluids and sufficient lipid solubility to cross biological membranes
• dissolved solutes permeated epithelial membranes by:

  Passive diffusion:

  • transcellular diffusion across the cell membrane
  • paracellular diffusion between cells

  Carrier mediated transport

  Cytosis
• how do most drugs cross the epithelial membrane?

  via transcellular permeation or diffusion across the lipid bilayer
• the ability of drugs to diffuse via the transcellular route is favoured by what type of drugs?

  for uncharged drugs with higher lipid solubility, lower molecular weight
• Movement of water and hydrophilic, low molecular weight solutes occurs through the tight junctions between cells - these channels, known as the paracellular route, open and close in response to various physiological stimuli
• paracellular route in different tissues:

  • stratum corneum: the paracellular channels are filled with lipids (limit drug diffusion)
  • capillary membranes allow solutes as large as 5000 D through their intercellular clefts
• Carrier mediated transport...

  • drug molecules bound to a specific protein site
  • down or against a concentration gradient
  • e.g. the absorption of metformin
• endocytosis and transcytosis are methods used to transport what?

  transport large macromolecules like amino acids
• what is endocytosis?

  membrane transport mechanism in which a macromolecule or particle is engulfed by a segment of the cell’s plasma membrane which then pinches off to form a vesicle inside the cell
• what is transcytosis?

  membrane transport mechanism in which a macromolecule or particle is engulfed by a segment of the cell's plasma membrane. This segment then pinches off to form a vesicle, facilitating the transfer of the macromolecule or particle to the other side of the cell
• what are the labels?

  A) endocytosis

  B) transcytosis

  
• drugs are released from the dosage form by which processes?

  dissolution and diffusion
• What does it mean if a drug is classified as Class I? (BCS classification)

  High solubility/high permeability

  e.g. beta blockers
• What does it mean if a drug is classified as Class II? (BCS classification)

  low solubility/high permeability

  e.g. NSAIDs (non-steroidal anti-inflammatory)
• What does it mean if a drug is classified as Class III? (BCS classification)

  high solubility/low permeability

  e.g. H2 antagonists
• What does it mean if a drug is classified as Class IV? (BCS classification)

  low solubility/low permeability

  e.g. diuretics
• when is a drug considered to be highly soluble?

  A drug is considered to be highly soluble when the highest dose strength is soluble in 250 mL or less of an aqueous medium over the pH range from 1 to 7.5
• when is a drug considered to be highly permeable?

  A drug is considered to be highly permeable when the extent of absorption in humans is greater than 90% of the administered dose