GPAT Dispensing and Hospital Pharmacy Syllabus

What do 'over proof' (OP) and 'under proof' (UP) mean?

OP = stronger than proof spirit; UP = weaker than proof spirit; the percentage states how far above or below proof the strength is.

Why does volume contraction occur when alcohol and water are mixed?

Hydrogen bonding and tighter molecular packing between ethanol and water make the final volume less than the sum of the two starting volumes.

Because of contraction in volume, how should an alcohol dilution be prepared accurately?

Make up to the final required volume with water (q.s. to volume) rather than simply adding the calculated volume of water.

What is the difference between % v/v and % w/w for alcohol?

% v/v = mL of alcohol per 100 mL of solution; % w/w = g of alcohol per 100 g of solution. They differ because ethanol and water have different densities.

How much 95% alcohol is needed to prepare 1000 mL of 50% alcohol?

V1 = C2V2/C1 = (50x1000)/95 = 526.3 mL of 95% alcohol, then q.s. to 1000 mL with water.

To what volume can 500 mL of 90% v/v alcohol be diluted to obtain 70% v/v?

V2 = C1V1/C2 = (90x500)/70 = 642.9 mL of 70% alcohol (make up to this volume with water).

What is absolute alcohol?

Ethanol containing not less than 99.5% v/v of ethyl alcohol (essentially water-free).

What is rectified spirit?

Ethanol of about 90% v/v (roughly 95% by some specifications) obtained by rectification, i.e. fractional distillation.

Why can ordinary distillation not produce absolute alcohol?

Ethanol and water form an azeotrope at about 95.5% v/v, so distillation cannot exceed this strength; further dehydration is required for absolute alcohol.

Express the quantity of absolute alcohol for a solution of strength S and volume V.

Quantity of absolute alcohol = (S/100) x V; this value remains constant when the solution is diluted with water.

How many mL of 60% alcohol can be made from 200 mL of 90% alcohol?

V2 = (90x200)/60 = 300 mL.

How does the specific gravity of alcohol change as its strength increases?

It decreases, because ethanol is less dense than water, so higher-strength alcohol has a lower specific gravity.

Why is weighing preferred over measuring by volume for accurate alcohol dilutions?

Weighing eliminates errors caused by contraction in volume, since masses are additive while volumes are not.

Define an isotonic solution.

A solution having the same osmotic pressure (tonicity) as body fluids such as blood and tears, so cells neither swell nor shrink.

What is the isotonic concentration of sodium chloride?

0.9% w/v NaCl (normal saline).

What freezing point depression value is used as the reference for isotonicity with body fluids?

0.52 degrees C; a solution that freezes at -0.52 degrees C is isotonic with blood and tears.

Define a hypotonic solution and its effect on red blood cells.

It has lower osmotic pressure than blood; water enters the cells, causing them to swell and undergo hemolysis (bursting).

Define a hypertonic solution and its effect on red blood cells.

It has higher osmotic pressure than blood; water leaves the cells, causing them to shrink (crenation).

What is the sodium chloride equivalent (E value) of a drug?

The weight of NaCl that produces the same osmotic effect as 1 gram of the drug.

Give the formula for NaCl needed for isotonicity using sodium chloride equivalents.

NaCl required = (0.009 x volume in mL) - sum of (E value x weight of each drug); i.e. the 0.9% NaCl requirement minus the NaCl equivalent contributed by the drugs.

Name the four methods used to adjust the tonicity of solutions.

Class I: Sodium chloride (NaCl) equivalent method and Freezing point depression (cryoscopic) method. Class II: White-Vincent method and Sprowls method.

What principle does the freezing point depression (cryoscopic) method rely on?

That 0.9% NaCl and body fluids both depress the freezing point by 0.52 degrees C; the adjusting substance is added to bring the total depression to 0.52 degrees C.

State the freezing point method formula for the % of adjusting substance needed.

W = (0.52 - a)/b, where a = freezing point depression caused by the drug, b = freezing point depression of a 1% solution of the adjusting substance, and W = % w/v of adjusting substance required.

What is the White-Vincent method?

A method that finds the volume of isotonic solution obtainable from a given weight of drug using V = w x E x 111.1, after which the solution is made up to final volume with an isotonic vehicle.

In the White-Vincent method, what does the constant 111.1 represent?

The volume in mL of isotonic solution produced by 1 g of NaCl, since 0.9 g NaCl makes 100 mL isotonic, so 1 g makes 100/0.9 = 111.1 mL.

What is the Sprowls method?

A simplification of the White-Vincent method that uses precalculated tables giving the volume of isotonic solution obtainable from 0.3 g of drug (the usual weight for 30 mL).

Why is tonicity adjustment important for ophthalmic and parenteral products?

To avoid pain, tissue irritation, and cell damage (hemolysis or crenation) by matching the product's osmotic pressure to that of body fluids.

What is the Liso value, and what is its value for NaCl?

Liso is the freezing point depression of a 1 molar solution at isotonic concentration; for NaCl (a two-ion electrolyte) Liso = 3.4.

Give the formula relating a drug's E value to its molecular weight and Liso.

E = 17 x (Liso / molecular weight of the drug).

How much NaCl is needed to make 100 mL of a 1% drug solution isotonic if the drug's E value is 0.20?

Total NaCl for 100 mL = 0.9 g; drug contributes 1 g x 0.20 = 0.2 g NaCl equivalent; so add 0.9 - 0.2 = 0.7 g NaCl.