week 1 / 2 phys pharm

Solids have

High intermolecular attraction and high potential energy » & little kinetic energy

Gas state particles have

High kinetic energy and little inter-molecular attraction

What state has the highest density

Solids — closely packed arrangement of particles

Permanent dipole

Covalent bond (strong)

Unequal charge distribution within a chemical bond leads to electrical dipole

Dipole is like a bar magnet and attracts other dipoles (intermolecular attraction forces)

Permanent dipole- permanent dipole

Keesom forces

One molecular dipole interacts w another molecular dipole » like 2 bar magnets attracting each other

These are weaker than H-bonds

Permanent dipole-induced dipole

Debye forces: neutral molecules can get polarized in presence of permanent dipole — like piece of metal being magnetized by strong bar magnet

Induced dipoles

London dispersion forces

Temporary dipole in one molecule distorts the e- cloud of neighboring molecule » this induces a matching dipole (London forces)

Elongated, linear molecules have stronger dispersion forces than compact, sphere molecules due to greater surface area contact and greater e- density

Vander waals forces : induced dipoles (2)

N-propranolol being linear is able to induce greater polarization vs branched isopropanol

This is why isopropanol has higher vapor pressure (evaporates quickly) vs n-propanol

so isopropanol can be used as a spray disinfectant for surface cleaning

Induced dipole interactions ..

Stabilize cell membranes

Lipid “tails” in a cell membrane induce dipoles in each other which = weak attraction forces

High # of interactions within very long lipid tails make the cell membrane stable

Permanent dipoles— H bonding

Water molecule is permanent dipole

H bonding is a special type of permanent dipole interaction

This bonding happens between highly electronegative atoms (O, N, F) of one molecule w H-atoms bound to another electronegative atom

Importance of H bonding

Gives structural stability for proteins and DNA

Double helix & alpha helical structures in proteins stabilized by H bonds

Allows them to uncouple easily during DNA replication

Heat can destabilize both of these macro molecules (disrupts H bonds)

Ion dipole interactions — NaCl in water

Ion-dipole force exists between a polar molecule and an ion

Anions: (-ve charge » attracted to the +ve end of a dipole & Cations (+ve charge » attracted to negative pole)

The greater the ionic charge / and or dipole strength…

Greater the attraction

Ion-dipole forces are important for solutions of ionic substances in polar liquids — like salt and water

In chemical series..

Compounds with similar molecular weights tend to have similar physical properties like melting/boiling point

This rule can be distorted by large intermolecular attraction forces

Ex: acetonitrile is very polar & high intermolecular interactions,, this leads to elevation in BP relative to other compounds shown

Solids are

Incompressible & have high potential energy

Atoms are

Fixed relative to each other and have little motion in solids

3 types of solids

Crystalline, amorphous, polymeric

Crystals» highly organized & sharp MP

Amorphous » irregular organization & no clear MP

Polymers» repetition of basic structure (cellulose, gums, starch) not a sharp MP

Crystalline solids..

Various arrangements (cubical, tetragonal, hexagonal)

Leads to different physical properties (MP/BP) — polymorphs

Diamond and graphite both made of C — but bc different lattice arrangements,, they are different in physical properties

Diamond and graphite are polymorphs

Ritonavir

Polymorphic crystalline solid

Some polymeric forms are more stable than others » a danger for inter-conversion of drugs from one form to another inside a dosage form

This can alter dosage form stability » drug form that is soluble previously may fall out of the formulation , which compromises the usefulness

Amorphous solids

Arranged in disorderly form

Amorphous (glass) forms

No sharp MP, but transition temp

More soluble & preferred

Less stable and can change forms over time

Polymers

Monomer links form » polymers

Physical properties depend on size of the n (peg200 vs peg3000)

Some compounds

Depress each others MP When mixed together

Eutectic point ( C ) » lowest MP for a mixture of solids

Methanol and camphor when mixed together » can become liquids (Eutectic mix)

Lidocaine & prilocaine (both solid) » become oil when mixed

Homomeric crystals»

Homogenous & contain one type of chemical

Heteromeric crystals…

Have other types of molecules (water or other ions) accommodated in crystal lattice » changed properties of hetero crystals give unique advantages over homo

Hygroscopic

When pure amoxicillin pull water from air which cause instability » trihydrate is more stable no pulling moisture

Solubility of atropine sulfate is higher than atropine free base

Liquids

More inter-particle attraction (PE) & less spontaneous motion (KE)

When gas is cooled…

Molecules lose much of kinetic energy » vander waals attraction forces take over & liquefy

Below certain critical temp» pressure may be applied to gas to liquefy it

No amt of pressure above the critical temp can liquefy the gas bc of excess kinetic energy

Liquids have PROPERTIES » vapor pressure, BP, FP, Surface tension, & viscosity

Within a liquid..

Kinetic energy is not uniform

Molecules at top have more energy to escape attraction forces and become vapor molecules ( evaporation)

Pressure exerted by the escaping vapor molecules is called vapor pressure

VP of liquid rises w increase in temp (more kinetic energy)

Some drugs have..

High VP and are potent, so they can pose a exposure risk during handling due to evaporation

Hazardous classes of drugs (anti-cancer)

Polyethylene glycol used to reduce VP of nitroglycerine

Handling of high VP drugs » require special care (fume hood)

Temp when VP = atmospheric pressure is

BP of the liquid

At BP » all energy used up by molecules to vaporize and no further increase in temp happens

Where atmospheric pressure is low,

BP is lower and at

High pressure, BP is higher

Surface tension

Molecules at surface are pulled inwards by other molecules inside the liquid

High surface tension =

Liquid resembles a stretched elastic membrane

Soap or surfactants » reduce surface tension of liquids like water and promote wetting/dissolution » skin disinfect before surgery

Viscosity

Fluids internal resistance to flow

Thickness

Tends to decrease with the increase in temp

gas molecules have ..

Little or no intermolecular attraction

Collisions against container= pressure

Pressure= force applied over an area (p=F/A)

Units of pressure : pascals, atmospheres, mm Hg, psi

Boyles law

V and P of gas inversely related

Charles law

V of gas is directly proportional to temp (T) in kelvin

Avagadros law

V of gas is proportional to # of moles (n)

PV=

nRT » universal gas equation

In aerosol dosage forms..

Propellant gases like chlorofluocarbons are liquified under high pressure (below critical temp) and drugs are dissolved in them

When actuated (release of pressure)

Compressed solvent rapidly expands and evaporates and delivers the drug as it escapes the inhaler

Aerosols need to be protected against high temp /low pressure to prevent exploding

Dalton’s law

Total pressure exerted by mix of gases = to sum of partial pressures of component gases

Ptotal= p1+p2….Pn

Henry’s law

Dissolved gas in liquid » directly proportional to pressure of gas above liquid

Increase of conc. of anesthetic gas » pressure is increased and anesthesia is deepened

O2 concentrators

Henry’s law applied

Dissolved oxygen in blood decreases rapidly w decrease in atmospheric pressure

Altitude sickness

Deep sea diver comes up quick» dissolved nitrogen tries to exit quick which leads to bubble formation and decompression sickness