Indiffusible Mixtures: The Practical

What makes an indiffusible mixture different?

An indiffusible solid is a heavy powder that sinks quickly and may pack into a hard cake. Common examples are chalk, calamine and zinc oxide. If it is put in water alone, each dose of the shaken bottle would contain a different amount of drug.

A suspending agent makes the liquid thicker and coats the particles, so they settle slowly and are easy to shake back. Common suspending agents are:

• compound tragacanth powder
• tragacanth and acacia
• sodium carboxymethylcellulose
• bentonite

The amount to use comes from the formula. A figure often quoted for compound tragacanth powder is about 2 g in 100 mL, but use the formula from the reference your school follows, and check it with the pharmacist.

Equipment

The equipment is the same as for a diffusible mixture: balance, mortar and pestle, measuring cylinder, glass rod, funnel and strainer, bottle and labels. Use a large enough mortar, because the mixture will need room for stirring.

Method

1. Calculate all the quantities, including the suspending agent, and have them checked.
2. Weigh the indiffusible powder and the suspending agent.
3. Powder the solid finely in the mortar.
4. Mix the dry powders together in the mortar. The suspending agent must be spread through the powder before any liquid is added.
5. Add the vehicle a little at a time, stirring to a smooth cream, then more liquid to make it thinner.
6. Dissolve the soluble ingredients in some vehicle separately, strain if needed, and add them.
7. Add the flavouring and any other liquids.
8. Transfer to a measuring cylinder, then rinse the mortar with vehicle and add the rinsings.
9. Make up to the final volume and stir well.
10. Bottle at once, close and label, with "Shake the bottle well before use".

Why mix the powders dry first?

A suspending agent such as tragacanth swells when it meets water. If water is poured on it alone, the outside of each grain swells into a sticky skin before the inside is wet, and lumps form that are very hard to remove. Spreading it through the other powder keeps the grains apart, so the liquid can wet them evenly.

Worked example: scaling the formula

This is an illustrative practice formula, not a pharmacopoeial one. Use the formula your school or pharmacist gives you.

Chalk mixture, 100 mL: chalk 4 g, compound tragacanth powder 2 g, cinnamon water to 100 mL. Make 250 mL.

1. Scale factor = 250 ÷ 100 = 2.5
2. Chalk = 4 × 2.5 = 10 g
3. Compound tragacanth powder = 2 × 2.5 = 5 g
4. Cinnamon water to 250 mL

Check. Chalk strength in the formula = 4 ÷ 100 × 100 = 4% w/v. In the scaled formula, 10 ÷ 250 × 100 = 4% w/v, which is the same.

If the dose is 10 mL, there are 250 ÷ 10 = 25 doses, so each dose contains 10 ÷ 25 = 0.4 g of chalk.

Labelling

The label shows the same details as for any mixture, with:

• "Shake the bottle well before use", which is vital for every suspension;
• the dose, in millilitres or 5 mL spoonfuls;
• the discard date and storage advice;
• any warning from the pharmacist.

Faults and what to do

Safety and records

• Chalk and other powders can be dusty. Weigh them carefully and avoid breathing the dust.
• Record the weights, the batch and the discard date.
• Let the pharmacist check the final product before it is given to the patient.
• Tell the patient to shake the bottle and to use a measuring spoon or oral syringe.