isotonicity,osmosis,types,route of administration freezing point depression ,calculation method and example
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Isotonicity
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 pressure is the force that cause this diffusion . Tonicity is a measure of the osmotic pressure of two solutions separated by a semi-permeable membrane.
Isotonicity & route of administration Subcu taneous 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.
Isotonicity & route of administration cont. Intrathecal injestion 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
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
Freezing point depression (f.p.d) Freezing Point solution = Freezing Point solvent - ΔT f ΔT f =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
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 )
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)
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
Example II adjust isotonicity of procaine HCl 3% using NaCl ? Fpd of 1%NaCl=0.57º, f.p.d of 1% drug=0.112º
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 1 st calculate E NaCl 2 nd add NaCl to reach 0.9%
How to calculate E NaCl ? =
How to calculate amount of NaCl
Example I Calculate E NaCl of drug (M.wt=187, L iso =3.4)? How much NaCl needed to make 2% of this drug isotonic?
Example II Calculate amount of NaCl needed to adjust 1.5% Atropine SO 4 (E NaCl =0.12gm) =0.9 –(W x E) = 0.9 –(1.5x 0.12) = 0.72 gm of NaCl should be added
3-White – Vincent method Principle: 1 st Addition of H2O to drug to make it isotonic 2 nd addition of isotonic vehicle to bring solution to final volume
How to calculate amount of H 2 O ? Suppose preparing 30ml of 1% drug isotonic with body fluid(E NaCl =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
One step equation V : volume of H 2 O W: weight of drug 111.1= 100/0.9 Last example
II example Add volume of H 2 O and then complete with isotonic solution Phenacaine HCl 0.06 gm ( E NaCl =0.16) Boric acid 0.3 gm ( E NaCl =0.5) sterile distilled H 2 O up to 100 ml V = 111.1 x(weight x E NaCl ) V =111.1 x [(0.06x0.16)+(0.3x0.5)] = 17.7 ml H 2 O