9/11 Drug Solubility and Formulation continued

… you skipped class… don’t do it again

for slide 26 to slide 6 for next part

Free energy transfer from non polar solvent to water is proportional to hydrophobic surface area

negative enthalpy (system is LOSING heat) —> exothermic

positive enthalpy (system is GAINING heat) —> endothermic

negative entropy (system is becoming more ordered)

positive entropy (system is becoming more disordered)

protein folding is exothermic (more favorable) bc water shit outside really does not like touching hydrophobic stuff and will freeze which requires even more energy

protein folder creates more entropy (more disorder)

  • doesn’t make sense bc wouldn’t it be more ordered?

  • no bc water molecules that were touchy earlier are unfrozen and can create more disorder

ΔG = ΔH – TΔS

ΔG negative is spontaneous

melting is endothermic (positive H)

therefore entropy outweighs for it to be spontaneous

Dissolution:

  • solvents dissolve solutes by overcoming solute-solute and solvent-solvent interactions

  • they both expand and intertwine kinda

Steps of Dissolution:

  1. need to separate intermolecular forces of solutes

  2. need to separate imf of solvents AND have big enough void space for a solute

  3. solute moves into void space

    1. if spontaneous, negative work

What affects Solubility?

  • polarity (if same polarity, they dissolve)

  • branched vs. straight

  • molecular weight

  • structural similarity

    • has to do with how solute and solvents interact

  • crystal structure

    • if it’s packed (uniform and regular), it’s less soluble

    • irregularity means more soluble bc some stuff is hanging off

What makes it more soluble in water? (high solubility)

  • high polarity (hydrophilic)

  • more branches

  • low molecular weight

  • inc structural similarity of solute and solvent

pH: weak acids and weak bases dissolve into —> ionized + unionized forms

  • solubility is the sum of those two forms

  • S = Si + S0

    • Si is ionized

    • S0 is unionized

  • when more ionized —> greater solubility

How to enhance solubility: Cosolvent

  • if hydrophobic + nonionizable —> insensitive to pH

  • adding cosolvent —> lower delectric constant

    • how much it can store energy (reduces it’s capacity)

    • be careful that the cosolvent isn’t toxic lol

    • have hydrophillic and hydrophobic parts so it gets in between to lessen imf so that the solute can dissolve

    • usually tinier than the solvent, basically if the solvent can not dissolve the solute, the cosolvent will be added which breaks up the solute-solute interactions and so it’s technically dissolved in the solvent (technically dissolved by the cosolvent)

Another way to enhance solubility: Surfactant

  • surfactants reduce surface tension bc they create micelles since they have hydrophilic heads outward and hydrophobic tails inward

  • nonpolar drug goes into the core, basically the micelle acts as an outer core that allows it to vibe inside the water and disperse

Yet ANOTHER way to enhance solubility: Nanosizing

  • dissolution rate is dependent on surface area of the medium it is in contant w/

  • dec drug size = inc SA to volume ratio + inc dissolution rate

need 38-40 + to slide 6 on next one owo good work

Polymorph (various crystalline forms)

  • pretty important work in looking into optimal ways to form the structure (salt, cosolvent, cocrystal)

  • different ways they dissolve or how well

Drug Stability:

  • temperature, heat, light, exposure, time can affect stability

  • amorphous drug dispersion (shit to add to the drug to make it soluble) fail over time which leads to more crystalline states (can’t dissolve in your blood) therefore drug is useless

new thing I learned:

  • the head facing outward is hydrophilic