1

 
Objec(ves:  
 

 
 Understanding   the   proper/es   of   gases   and   vapours,  
including   the   way   in   which   the   vapour   pressure   above  
solu/ons  varies  with  the  composi/on  of  the  solu/on  and  
the  temperature.    
 
 The  factors  controlling  the  solubility  of  gases  in  liquids  
are   reviewed   and   related   to   the   solubility   of   anesthe/c  
gases  in  the  complex  solvent  systems.    
 
 Formula/on  issues  of  gases  and  vapours.

2  
 Pressure  units  
Vapor   pressure,   the   pressure  
exerted   by   the   gas-­‐phase   molecules  
over  a  liquid.  

!   The   vapor   pressure   of   a   liquid   is  

measure  of  its  “vola/lity”  
 
!   Vapor   pressure   is   a   strong  
func/on   of   temperature—the   higher  
the   temperature,   the   higher   the  
vapor  pressure.  
 

!  The  SI  unit  is  the  pascal  (Pa)  

where  1  Pa  =  1  N  m-­‐2.  

3  
Standard  Atmospheric  Pressure    
760  mmHg  =  760  torr  =  1.013  bar  =  1.013  x  105  Pa  

Propellants  (chemical  substances)  can  be  measured  by  using  

“pound  per  square  inch  gauge  (psig)”    
 
The  atmospheric  pressure  at  sea  level  =  14.7  psi  
Absolute  pressure  in  pounds  per  square  inch  (psia)  =  psig  +  14.7    

Ideal  and  nonideal  gases  

An  ideal  gas,  the  collision  or  impact  between  the  gas  par/cles  are  
said   to   be   elas/c   (there   is   neither   aQrac/ve   nor   repulsive   energy  
included  throughout  the  collision  of  par/cles).  

PV=nRT  is  the  equa/on  of  ideal  gas  

4  
 EXAMPLE  2.1:  
Calculate  the  pressure  at  25°C  within  an  aerosol  container  of  internal  
volume   250   cm3   containing   160   cm3   of   concentrate   above   which   has  
been  introduced  0.04  mol  of  nitrogen  gas.  Assume  ideal  behaviour.  

A  nonideal  gas  (real  gas)  is  made  up  of  par/cles  or  molecules  that  may  
aQract   one   another   very   strongly   with   repulsive   energy   or   aQrac/ve  
force.  Example  (water  vapour,  ammonia,  sulfur  dioxide,  and  etc.)  
Dutch   physicist   Johannes   van   der   Waals   came   up   with   an   modified  
version  of  the  ideal  gas  equa/on  (PV  =  nRT):  
where  a  and  b  are  constants  for  a  
par/cular  gas  
5  
Comparison  between  ideal  and  real  gases:    

1. Ideal   gas   has   no   definite   volume   while   real   gas   has   definite  
volume.  
 

2. Ideal  gas  has  no  mass  whereas  real  gas  has  mass.  
3. Collision   of   ideal   gas   par/cles   is   elas/c   while   non-­‐elas/c   for  
real  gas.  
4. No   energy   involved   during   collision   of   par/cles   in   ideal   gas.  
Collision  of  par/cles  in  real  gas  has  aQrac/ng  energy.  
5. Pressure  is  high  in  ideal  gas  compared  to  real  gas.  
6. Ideal  gas  follows  the  equa/on  PV=nRT.  
Real  gas  follows  the  equa/on  (P  +  an2/V2)  (V  –  nb)  =  nRT.  

6  
 Compressibility  factor  (Z)    
The  pressure  normally  met  in  
pharmaceu/cal  systems  

For  ideal  gas  PV  =  nRT  

 
Divide  both  sides  by  
Small  gas  molecules  
nRT  
PV/nRT  =  1   Z  =  1  (ideal  gas  behavior)  

(compressibility  for   Large  gas  molecules  

ideal  gas  only  )  

7  
 Vapour  pressure  
Vapour  pressure  and  solu-on  composi-on:  Raoult’s  law  
Raoult's  law  is  important  because  it  allows  the  calcula/on  of  vapour  
pressure   above   an   aerosol   mixture   from   a   knowledge   of   the  
composi/on  of  the  solu/on:  

The  par/al  vapour  pressure  of  a  component  i  in  the  vapour  phase  

The  mole  frac/on  of  that  

component  in  solu/on,  xi  

The  vapour  pressure  of  the  pure  component  

EXAMPLE   2.2   Calcula(on   of   the   vapour   pressure   of   a   mixture   of   hydrofluoroalkanes  

Calculate  the  vapour  pressure  (in  Pa)  at  20°C  above  an  aerosol  mixture  consis/ng  of  30%  w/
w   of   HFA   134a   (tetrafluoroethane,   molecular   weight   102)   with   a   vapour   pressure   of   68.4  
psig   and   70%   w/w   of   HFA   227   (heptafluoropropane,   molecular   weight   170)   with   a   vapour  
pressure  of  56.0  psig.  Assume  ideal  behaviour.  
8  
 Varia(on  of  vapour  pressure  with  temperature:  
Clausius–Clapeyron  equa(on  
The   varia/on   of   vapour   pressure   with   temperature   may   be   expressed  
in   terms   of   the   molar   enthalpy   of   vaporisa-on   of   the   liquid,   ΔHvap,  
using  the  Clapeyron  equa/on  

• ΔV  is  the  difference  in  molar  volume  of  the  two  phases  
• Molar  volume  of  vapour  is  much  greater  than  the  molar  volume  of  
liquid,  ΔV  approaches  volume  of  vapour,  Vv    
• Assuming  that  the  vapour  obeys  ideal  gas  behaviour,  V  =  RT/P      

9  
General  integra-on,  assuming  ΔHvap  to  be  constant,  gives  

Log  P  

The  Clausius–Clapeyron  equa/on  is  useful  in  

the  calcula/on  of  the  enthalpy  of  vaporisa/on  

10  
 Applica(on  of  Clausius–Clapeyron  equa(on    
The  sublima/on  of  ibuprofen  

• Glass   vials   containing   solid  

ibuprofen   develop   a   haze   on  
their   inner   walls   when   stored   at  
40°C.   which   is   a   consequence   of  
sublima/on.  

EXAMPLE  2.3  Calcula/on  of  the  molar  

enthalpy  of  vaporisa/on  

The  slope  of  a  plot  of  log  P  against  1/T  

for  metamfetamine  is  -­‐  2.727  x  103  K.  
Calculate   the   molar   enthalpy   of  
vaporisa/on   of   this   compound   over  
the  given  temperature  range.  

11  
 Vapour  pressure  lowering  
Raoult’s   law   can   be   used   to  
calculate   the   lowering   of   vapour  
pressure  following  the  addi/on  of  a  
non-­‐vola.le  solute  to  a  solvent.  The  
equa/on  is,  
 
 
 
 
which   shows   that   the   rela/ve  
lowering   of   the   vapour   pressure   is  
equal  to  the  mole  frac/on  x2  of  the  
solute.  

12  
Boiling  point  eleva(on  
• A  solu/on  always  boils  at  a  higher  temperature  than  the  pure  solvent.  
• This  colliga/ve  property  is  a  result  of  the  vapure  pressure  lowering.  
• The  boiling  point  eleva/on  is  propor/onal  to  the  molality  of  the  solu/on  

Where  Kb  is  the  molal  eleva/on  constant,  which  has  the  value  0.511  
K  mol-­‐1  kg  for  water.  

The  freezing  point  of  the  solu/on  is  lower  than  that  of  the  pure  
solvent.  

Where  Kf  is  the  molal  freezing  point  constant,  which  is  1.86  K  
mol-­‐1  kg  for  water.  

13  
Q1:  What  is  the  boiling  point  eleva/on  when  11.4  g  of  ammonia  (NH3)  
is  dissolved  in  200  g  of  water?  Kb  for  water  is  0.51  0C/m.  
 
 
 
 
 
 
Q2:  How  many  grams  of  benzoic  acid  (C7H6O2)  must  be  dissolved  in  
78.1  g  of  ethanol  to  rise  the  boiling  point  by  4.0  0C?  Kb  for  ethanol  is  
1.20  0C/m.  

14  
Solubility  of  gases  in  liquids  
The   solubility   of   gas   in   liquid   expressed   by   Bunsen’s   absorp(on  
coefficient,   a,   which   is   the   volume   of   gas   reduced   to   273   K   and   a  
pressure  of  1  bar  which  dissolves  in  a  unit  volume  of  the  liquid  at  the  
given   temperature   when   the   par/al   pressure   of   the   gas   is   1   bar.  
(Standard  temperature  and  pressure  of  dissolved  gas)  

If  the  solubility  of  N2  in  water  at  25°C  and  a  nitrogen  pressure  
of  450  torr  is  0.378  mol  m-­‐3,  calculate  the  Bunsen  coefficient.  

In   anesthe/c   prac/ce,   an   alterna/ve   solubility   coefficient,   the  

Ostwald  solubility  coefficient,  is  preferred.  
The   volume   of   gas   is   not   corrected   to   standard   temperature  
and  pressure  but  instead  is  measured  at  the  temperature  and  
pressure  concerned.  
15  
Effect  of  temperature  on  solubility  
• When   gases   dissolve   in   water   without   chemical   reac/on  
there  is  generally  an  evolu/on  of  heat.    
• The   effect   of   temperature   on   the   absorp/on   coefficient  
may   be   determined   from   an   equa/on   analogous   to   the  
van’t  Hoff  equa/on:  

where  a1  and  a2  are  the  absorp(on  coefficients   at  temperature  

T1   and   T2   ,   respec/vely,   and   ΔH   is   the   change   in   enthalpy  
accompanying  the  solu/on  of  1  mole  of  gas.  
• As   temperature   increases   the   solubility   of   gas   in   liquid  
decreases.  
16  
Effect  of  pressure  on  solubility  

The  influence  of  pressure  on  solubility  is  expressed  by  Henry’s  
law  
where  k  is  a  propor/onality  constant.  

EXAMPLE  2.5  Henry’s  law  calcula(on  

The   solubility   of   oxygen   in   water   at   a   par/al   pressure   of   25  
torr   is   8.31   mg   dm-­‐3   at   25°C.   Calculate   the   solubility   if   the  
par/al   pressure   is   increased   to   100   torr   at   the   same  
temperature.  

17  
The  solubility  of  vola(le  anesthe(cs in  oil  (lipid)  
Oil/  gas  par((on  coefficient:  
• It   is   a   measure   of   lipid   solubility   of   the   anesthe/c   (indicates   the  
amount  of  gas  that  is  soluble  in  lipid  phase  )  
• As  solubility  of  anesthe/cs  increases  in  lipid  the  potency  increases    
minimum  alveolar  concentra(on  
(MAC)  
• Anesthe/c   dose   is   expressed   in  
terms   of   the   MAC,   the   minimum  
concentra/on   of   inhaled   gases   that  
is  represented  by  anesthe/c  gas  at  1  
atm   (prevent   muscle   movement).  
Example,   methoxyflurane   MAC   =  
0.16%,   it   means   only   0.16%   of   the  
molecules  of  inspired  gas  need  to  be  
methoxyflurane.  
18  
The  solubility  of  gases  in  blood  and  (ssues  
The  solubility  of  oxygen  in  the  blood  

• The   solubility   of   oxygen   in   the  

blood   is   dependent   upon   the  
concentra/on   of   haemoglobin,  
each  gram  of  Hb  can  combine  
with   1.34   cm3   of   oxygen   at  
37°C  (Oxygen  satura/on,  So2)  

• The  color  of  blood  depends  on  

the  oxygen  combined  Hb.  
The   par/al   pressure   of   oxygen   in   the   inspired   air  
(approximately  147  torr  at  37°C),  allows  an  assessment  of  the  
gas  exchanging  func/on  of  the  lungs.  
19  
 The  solubility  of  gases  in  blood  and  (ssues  
The  solubility  of  oxygen  in  the  blood  

Mohr  effect:  

• Increased   CO2   levels  

lowers   the   pH   of   the  
blood.  
• This   effects   the   ability  
of  Hb  to  transport  O2.  
• A  lower  pH  causes  the  
Hb   to   release   more  
O2.  
• A   higher   pH   causes  
the   Hb   to   hold   onto  
more  O2.    

20  
 The  solubility  of  anesthe(c  gases  in  blood  and  (ssues  
Blood  solubility  and  anesthe(c  ac(on  

Alveolar  concentra/on  of  anesthe/c    

More  Soluble  in  blood:  

as  a  %  of  inspired  concentra/on  

• Slower  induc/on  
• Slower  recovery  
• Ex.,  Ether,  Halothane  

Less  Soluble  in  blood:  

• Faster  induc/on  
• Faster  recovery  
• Ex.,  N2O  

21  
End of Chapter 2.