Extemporaneous spironolactone suspension for a paediatric in-patient
A 2-year-old girl weighing 11 kg is admitted to the paediatric ward of an ESIC hospital with ascites complicating nephrotic syndrome. The nephrologist prescribes spironolactone 2 mg/kg/day in two divided doses. The hospital pharmacy stocks only spironolactone 25 mg tablets; no commercial oral liquid is available anywhere in the city and the child spits out crushed tablets mixed with milk. The pharmacy has a compounding bench, a calibrated electronic balance, a 100 mL graduated cylinder, a mortar and pestle, purified water, simple syrup, and a commercially available preserved suspending vehicle that is sorbitol-free (contains methylparaben and propylparaben). There is no fume hood and no facility to assay the finished preparation. The ward wants the first dose within two hours and enough preparation to last until discharge in about ten days. A nasogastric tube is in place, although the child is currently taking oral feeds.
1. Calculate the child's dose and propose a practical strength for the compounded suspension. Give a complete formula for a 100 mL batch, the volume of each dose, and the compounding steps.
Read the worked answer
Dose calculation. 2 mg/kg/day × 11 kg = 22 mg/day, i.e. 11 mg per dose, twice daily.
Strength selection. A 5 mg/mL suspension gives 11 ÷ 5 = 2.2 mL per dose, which can be measured accurately in a 5 mL oral syringe graduated to 0.1 mL. A 1 mg/mL strength would need 11 mL per dose - too large for a toddler. 5 mg/mL is therefore the practical choice.
Formula for 100 mL. 100 mL × 5 mg/mL = 500 mg of spironolactone = 20 tablets of 25 mg (verify the actual tablet label claim before weighing, since tablets are within 95–105% of claim).
Method. Triturate 20 tablets to a fine, uniform powder; mix to a smooth paste with about 20 mL of the suspending vehicle; add vehicle in geometric increments, transferring to the graduated cylinder and rinsing the mortar three times; make up to 100 mL with vehicle; transfer to an amber bottle with a child-resistant closure.
Label. 'Spironolactone 5 mg/mL oral suspension - SHAKE WELL - refrigerate - discard after 14 days - dose 2.2 mL twice daily.' A 100 mL batch gives about 45 doses; since only 20 doses are needed, a 50 mL batch is more economical and reduces wastage, but 100 mL is acceptable if a graduated cylinder of that size is the only calibrated one available.
2. Justify the choice of vehicle and the beyond-use date. Without an HPLC, what quality checks can you actually perform before the first dose is released?
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Vehicle. Spironolactone is practically insoluble in water, so the product must be a suspension, not a solution; the drug must be wetted and kept uniformly dispersed. The preserved commercial suspending vehicle supplies a structured suspending agent plus parabens, and being sorbitol-free it avoids osmotic diarrhoea in a toddler. Simple syrup alone would be a poor suspending agent, is highly cariogenic and adds an unnecessary osmotic load, so it is used only as a diluent if the vehicle runs short - not as the main vehicle.
Beyond-use date. For a non-sterile, water-containing oral liquid the default is 14 days refrigerated when preservative efficacy has not been demonstrated for this formulation. The parabens were validated in the vehicle, not with a high solid load of tablet excipients that can adsorb preservative, so the conservative 14-day refrigerated date is the defensible one; it comfortably covers the 10-day need.
Release checks possible without HPLC:
- Visual appearance, absence of visible particles or grit, and colour consistency.
- pH by indicator strip (should stay mildly acidic to neutral; a shift suggests instability).
- Volume delivered against the graduated cylinder.
- Resuspendability after 10 minutes standing and after shaking.
- Dose uniformity by weight: pipette ten 2.2 mL aliquots, weigh each, and compute the RSD; an RSD below about 5% supports adequate mixing and transfer.
Document all of it; the absence of an assay is an accepted limitation of extemporaneous compounding, not a reason to delay therapy.
3. The nurse asks (a) whether the dose can be given down the nasogastric tube along with the feed, and (b) whether a syringe of the dose can be kept at the bedside for the night shift. Answer both and state what should be monitored.
Read the worked answer
(a) Tube administration. Yes, but not mixed into the feed. Shake the bottle vigorously, measure 2.2 mL, dilute with 10–15 mL of water, flush the tube with 15–20 mL of water before and after, and give it separated from the feed by at least 30 minutes. Never add the suspension directly to a feed container: it will adhere to the tubing and the delivered dose becomes unpredictable. Spironolactone is best given with or just after food.
(b) Bedside storage. No. A pre-drawn syringe left at room temperature overnight is a microbial and dosing risk, and the drug settles. The bottle stays refrigerated, is shaken immediately before each dose, and the remainder is discarded at 14 days or earlier if the appearance changes; it must not be frozen.
Monitoring.
- Serum potassium - this is a potassium-sparing diuretic and the child has nephrotic syndrome; hyperkalaemia is the main hazard.
- Renal function and urine output - rising creatinine means the dose or drug needs review.
- Weight, abdominal girth and oedema to judge effect.
- Bowel habit - diarrhoea would suggest the vehicle or dose is a problem and, in a child on diuretics, dehydration.
Tell the nurse to report the actual measured dose volume back to the pharmacy if the child's weight changes, because the dose is weight-based.