1.
Isotonicity 1

2. Learning Objectives for these classes*
Define the term ‘iso-osmotic’
Define isotonic and differentiate from iso-osmotic
Explain the mechanism of action of hypertonic and hypotonic solutions on RBCs
Explain what strategies are used to make hypertonic and hypotonic solutions isotonic
Define osmolarity and osmolality
Be able to use equations involving Ciso%, FD1%, and SCE.
Describe how one can measure isotonicity of biological fluids
*in addition to: Before our next class you need to be able to

3. Before our next class you need to be able to*:
Define a) hypertonic, and b) hypotonic
Explain why a solution containing 2 mM glucose (impermeable) and 2 mM boric acid (permeable) is hypotonic to a solution containing 3 mM sucrose (impermeable).
Explain what happens to red blood cells when they are immersed in a hypotonic solution or a hypertonic solution
Calculate Ciso for each of the classes of L
* not all the answers are in these notes, you might need to look elsewhere

4. For more information
Martin, “Physical Pharmacy,” second half of Chapter 8, i.e., ignore the section on buffered solutions (eg in 4th Ed, read from p. 180 on)
Florence and Attwood, “Physicochemical Principles of Pharmacy” Ed 4, pp 69-75

5. Questions and Feedback

6. Some preparations that may require tonicity adjustment.
Injections, particularly IM( intra-muscular), SC (subcutaneous) and large volume IV (intravenous) injections
Eye drops
Eye lotions
Bladder irrigations
Nose drops

7. A solution with a higher concentration of impermeable solutes compared to red blood cells is said to be: A:
hypotonic B:
hypertonic C:
isotonic D:
iso-osmotic

8. Solution A contains 2 mM sucrose (impermeable) and 3 mM of urea (permeable); while solution B contains 5 mM dextrose (impermeable) A:
A is hypotonic to B B:
A is hypertonic to B C:
A is isotonic to B D:
A is iso-osmotic to B

9. Under isotonic conditions Liso for a new drug is 2
Under isotonic conditions Liso for a new drug is 2.0, therefore Ciso is A:
0.9 B:
3.85 C:
1.04 D:
0.26

10. A higher than usual Packed Cell Volume result means the blood cells were placed in a
hypotonic solution B
hypertonic solution C
iso-osmotic solution D
isotonic solution

11. Hypotonic solutions Group discussion (5 minutes)
What would happen to red blood cells if they were immersed in a hypotonic solution?

12. Preparation of Isotonic Solutions
Hypotonic solutions are usually made isotonic with body fluids by adding some therapeutically inactive solute.
e.g., dextrose or NaCl for intravenous use
boric acid or NaCl for ophthalmic use
Hypertonic solutions are usually made isotonic with body fluids by dilution with water.

13. Conditions for isotonicity
Solutions which are iso-osmotic with body fluids are only considered to be isotonic if :
membranes are impermeable to the solute (urea, boric acid, hexamine can pass thru RBC membranes)
the solute does not alter the permeability of membranes (ethanol, some anaesthetics, and propylene glycol can increase the permeability)
no chemical reaction leads to a change in the total concentration of dissolved ions or molecules.

14. Ciso So from before ΔTf = Lc
So under isotonic conditions ΔTf = Lisociso
Rearranging Ciso = 0.52/ Liso
In general, Liso may be grouped as
1.9 for non-electrolytes
2.0 for weak electrolytes
3.4 for uni-univalent electrolytes, eg NaCl
Higher values for electrolytes of higher valency
So if know Liso for class of additive can calculate isotonic concentration

15. Ciso example Calculate Ciso for NaCl, dextrose and boric acid.
Liso (NaCl) = 3.4, Liso (dextrose) = 1.9, Liso (boric acid)
Ciso = 0.52/ Liso
The isotonic concentration of NaCl is 0.15 M, of dextrose is 0.27 M, and of boric acid is 0.29 M

16. Calculation of isotonic composition from freezing point data
A 1% solution of sodium chloride in water has a measured freezing point depression of 0.576º C, i.e, FD1% = 0.576º C
What is the percentage composition of NaCl required in an aqueous solution to be isotonic with serum?
Ciso NaCl = (0.52 /0.576) x 1% from 1% NaCl = °C
= 0.90%. ΔTf(iso) = 0.52 °C
This is the accepted value (w/v) of a sodium chloride solution that is isotonic to body fluids.

17. example
A 1% solution of atropine sulfate in water has a measured freezing point depression of 0.07º C.
What is the percentage of atropine sulfate required in an aqueous solution to be isotonic with serum?
Ciso atropine sulfate = (0.52 /0.07) x 1%
= 7.4%

18. example – multi-component formulations
You are asked to make a 3% morphine sulfate (Ciso = 6.5%) isotonic by adding NaCl. How much NaCl do you need?
CisoNaCl = 0.9%, %NaCl = ?