Isotonicity

1. Isotonicity PHT 434

2. osmosis • Osmosis is the diffusion of solvent through a semi-permeable membrane. • Water always flows from lower solute concentration [dilute solution] to higher solute concentration until a balance is produced • Osmotic pressureis the force that cause this diffusion . • Tonicity is a measure of the osmotic pressure of two solutions separated by a semi-permeable membrane.

3. Types of Tonicity

4. Why using isotonic solutions?

5. Isotonicity & route of administration • Subcutaneous injection: • not necessarily “small dose” but isotonicity reduce pain. • Hypodermoclysis • should be isotonic “Large volume” • Intramuscular injection • should be isotonic or slightly hypertonic to increase penetration • Intravenous injection • should be isotonic “Large volume ” • Hypotonic cause haemolysis • Hypertonic solution may be administered slowly into a vein • Hypertonic large volume administered through a cannula into large vessels.

6. Isotonicity & route of administration cont. • Intrathecal injection • Should be isotonic • Eye drops • Rapid diluted by tear, but most of it is isotonic to decrease irritation • Eye lotions • Preferably isotonic • Nasal drops • Isotonic, but not essentially

7. Classes of adjustment of isotonicity • Class I • Adding substace • to lower f.p of solution to -0.52º • Freezing point depression (FPD) “cryoscopic method”. • NaCL equivalent method. • Class II • Adding H2O • White –Vincent method

8. Freezing point depression (f.p.d) • Freezing Pointsolution = Freezing Pointsolvent - ΔTf • ΔTf =L c L : constant , c : conc.(molarity) • It is Colligative property • Depend on concetration • same f.p.d same conc. same tonicity • 0.9% NaCl is isotonic i.e. F.p.d = 0.52º

9. 1- Freezing point depression (FPD) “cryoscopic method”. • F.P. of blood & tears = - 0.52º • Any solution have F.P. = - 0.52º is isotonic. • Any solution have F.P. › - 0.52º is hypotonic • - 0.4º hypotonic • -0.6º hypertonic • Add solute to hypotonic solution to reach f.p.d of blood (- 0.52º )

10. How to calculate? = conc. gm/100 ml of adjusting substance = f.p.d of 1% of unadjusted substance(table) X percentage strength = f.p.d of 1% of adjusting substance (table)

11. Example I • How much NaCl is required to render 100 ml of a 1% soln. of apomorphin HCL isotonic? • F.p.d of 1%NaCl=0.58º, F.p.d of 1%drug=0.08º • 1% drug 0.08º (0.52º- 0.08º=0.44º) • 1% NaCl 0.58º w% NaCl 0.44º

12. Example II • adjust isotonicity of procaine HCl 3% using NaCl ? Fpd of 1%NaCl=0.57º, f.p.d of 1% drug=0.112º

13. 2-NaCl equivalent method • NaCl equivalent “E” Amount of NaCl that is equivalent to(i.e., has the same osmotic effect (same f.p.d) as ) 1 gm of drug • 1st calculate E NaCl • 2nd add NaCl to reach 0.9%

14. How to calculate ENaCl ? =

15. How to calculate amount of NaCl

16. Example I • Calculate ENaCl of drug (M.wt=187, Liso=3.4)? • How much NaCl needed to make 2% of this drug isotonic?

17. Example II • Calculate amount of NaCl needed to adjust 1.5% Atropine SO4 (ENaCl =0.12gm) • =0.9 –(W x E) = 0.9 –(1.5x 0.12) = 0.72 gm of NaCl should be added

18. 3-White – Vincent method • Principle: • 1st Addition of H2O to drug to make it isotonic • 2nd addition of isotonic vehicle to bring solution to final volume

19. How to calculate amount of H2O ? • Suppose preparing 30ml of 1% drug isotonic with body fluid(ENaCl =0.16gm) • 1gm 100ml ? 30ml =0.3gm • Amount of NaCl eq. to 0.3 drug = 0.3 x 0.16 =0.048gm • 0.9 gm 100 ml • 0.048 gm ? ml =5.3 ml

20. One step equation V : volume of H2O W: weight of drug 111.1= 100/0.9 • Last example

21. IIexample Add volume of H2O and then complete with isotonic solution Phenacaine HCl 0.06 gm (ENaCl=0.16) Boric acid 0.3 gm (ENaCl=0.5) sterile distilled H2O up to 100 ml V = 111.1 x(weight x ENaCl) V =111.1 x [(0.06x0.16)+(0.3x0.5)] = 17.7 ml H2O