Small-Scale Production of Liquid Dosage Forms
8 minute read
What you will learn
- Describe how small-scale liquid production differs from extemporaneous dispensing
- Scale a formula up to a batch
- List the equipment used for solutions, suspensions and emulsions
- Describe the steps of production and in-process checks
- Calculate batch quantities, number of bottles and yield
- State the records and hygiene needed
Key points
- Small-scale production makes a batch of a product for several patients or a unit, not for one patient.
- Every ingredient is scaled by the same factor from the master formula.
- Solutions are made by dissolving, suspensions by dispersing with a suspending agent, and emulsions by homogenising oil, water and an emulsifier.
- In-process checks include appearance, volume, pH, relative density and fill volume.
- Batch records, labels and batch numbers allow every batch to be traced.
- Hygiene is critical, because water-based liquids support germs.
- Yield compares what you obtained with what you expected.
Extemporaneous and small-scale production
| Extemporaneous dispensing | Small-scale production | |
|---|---|---|
| Quantity | One prescription | A batch for several patients or a unit |
| When | When the prescription comes | In advance, as a stock |
| Records | Dispensing record | Batch record with a batch number |
| Checks | Pharmacist's check | In-process and final checks |
| Shelf life | Short | Set by the formula and stability data |
Hospital pharmacies often make small batches of products that are not available or are costly, such as mixtures, syrups and mouthwashes.
Scaling a formula
Every ingredient is multiplied by the same factor.
scale factor = batch size ÷ master formula size
Worked example
A syrup has 125 mg of drug in each 5 mL. Make a 10-litre batch.
- 125 mg ÷ 5 mL = 25 mg per mL
- Batch = 10 litres = 10 000 mL
- Drug = 25 × 10 000 = 250 000 mg = 250 g
The batch is filled into 100 mL bottles.
- Number of bottles = 10 000 ÷ 100 = 100 bottles (if there is no loss)
96 bottles are filled.
- Yield = 96 ÷ 100 × 100 = 96%
Some loss is expected (liquid left in the vessel, pipes and filters). A low yield is investigated.
Making each type
Solutions
- Weigh the solids, measure the liquids.
- Dissolve in part of the vehicle in a mixing tank, with a stirrer, crushing large crystals first. Use gentle heat only if the formula allows.
- Filter or strain if needed.
- Add liquids, flavours and preservatives.
- Make up to volume, and mix.
Suspensions
- Powder and sieve the solid.
- Mix with the suspending agent, then wet and disperse in the vehicle.
- Mix until smooth, and add the other ingredients.
- Make up to volume and keep stirring while filling, so that the powder does not settle.
Emulsions
- Prepare the oil phase and the water phase, with the emulsifier in the right phase, and heat if the formula says.
- Mix to form the primary emulsion.
- Pass through a homogeniser or colloid mill to break the droplets into small ones.
- Cool, add the preservative and flavour, and fill.
Equipment
| Equipment | Use |
|---|---|
| Mixing tank with stirrer (stainless steel) | Dissolving and mixing |
| Jacketed vessel | Heating or cooling |
| Homogeniser, colloid mill | Emulsions and fine suspensions |
| Filter press, cartridge filter | Clarifying |
| Filling machine | Fills bottles to a set volume |
| Capping and labelling equipment | Closing and labelling |
All equipment must be clean, suitable (stainless steel, glass) and dedicated or properly cleaned between products.
In-process and final checks
- Appearance: colour, clarity, particles, uniformity.
- pH, where it matters.
- Relative density (specific gravity).
- Fill volume: check bottles at intervals.
- Closure and leaks.
- Label: correct product, strength, batch number and expiry.
- Samples are kept, and tests for quality are done as the protocol states.
Records and hygiene
- Use an approved master formula and a batch record signed at each step.
- Give every batch a batch number and expiry date.
- Keep clean working areas, wear clean clothes and gloves, and use purified water.
- Label the equipment with the product being made, and clear the area before starting the next one, so that there are no mix-ups.
Exam focus
- Scale a formula to a batch size, and calculate the amount of drug.
- State the equipment for mixing and homogenising.
- Calculate the number of bottles filled and the percentage yield.
- Common mistake: scaling the drug but not the other ingredients.
Quick check
Test yourself before you move on. Pick an answer to see the explanation.
1.A syrup contains 125 mg of drug in each 5 mL. How much drug is needed for a 10 litre batch?
2.A 10 litre batch is filled into 100 mL bottles. How many bottles are filled if there is no loss?
3.96 bottles were filled from a batch that should give 100 bottles. What is the yield?
4.Which equipment helps to make a fine emulsion on a larger scale?
5.Why is a batch number put on each bottle?