Paediatric capsule compounding in hospital practices: by weight or by volume?

OBJECTIVE: Capsule compounding is common for paediatric patients. In Europe, pharmacists often use a volume-based method whereas, in the USA, the weight-based method prevails. These two methods should be compared in order to help hospital pharmacists to make their choice. METHODS: We evaluated the difference between the volume-based method and the weight-based method with 10 mg spironolactone capsules. Six independent batches were made with each technique and their conformity was evaluated with a high-performance liquid chromatography assay. RESULTS: The weight-based method showed superiority over the volume-based method for the following parameters: spironolactone content homogeneity, total weight content homogeneity, batch reproducibility and batch conformity. No differences were seen in spironolactone content between the two methods, but an overall trend towards underweighing the excipient was found with the volume-based method. CONCLUSIONS: Capsule compounding with the weight-based method increases the quality of the resulting formulation. The weight-based method requires knowledge of the galenic parameters of the active pharmaceutical ingredient and excipients, but should be preferred to the volume-based method.

Pre-formulation and Stability Study of 20-mcg Clonidine Hydrochloride Pediatric Capsules.

OBJECTIVE: Clonidine hydrochloride is an antihypertensive, centrally acting α2 adrenergic agonist with various pediatric indications. For pediatric patients, 20-mcg clonidine hydrochloride capsules can be compounded from commercial tablets or from a pre-compounded titrated powder. These methods should be compared to ensure the best quality for the high-risk patients, and a beyond-use date should be established. METHODS: Eight experimental batches were made from commercial tablets and 8 were made from microcrystalline cellulose (MCC)-based titrated powders. Quality controls were performed to determine the best compounding protocol. Stability study was conducted on capsules compounded with the best method. RESULTS: Of 8 batches manufactured from commercial tablets, 7 were compliant for both clonidine mean content and content uniformity, whereas 7 of 8 batches manufactured from titrated powders were not. A clonidine loss during compounding was evidenced by surface sampling analyses. Clonidine hydrochloride 20-mcg capsules' mean content remained higher than 90% of initial content for 1 year when stored at 25°C with 60% relative humidity and protected from light. CONCLUSIONS: Commercial tablets should be preferred to 1% clonidine hydrochloride and MCC titrated powder made from the active pharmaceutical ingredient. Twenty-microgram clonidine hydrochloride capsules made from commercial tablets are stable for 1 year when stored under managed ambient storage condition.

Stability Studies of Fludrocortisone Acetate Capsules and Fludrocortisone Acetate Titrated Powders (Powder Triturates).

Fludrocortisone acetate is a drug used to treat adrenal insufficiencies which can be prescribed to hospitalized or ambulatory pediatric patients at dosages not commercially available. For these patients, 10-µg fludrocortisone capsules are currently compounded from a pre-compounded titrated powder (powder triturate). Fludrocortisone stability studies were carried out to ensure a valid beyond-use date. First, a stability-indicating fludrocortisone acetate dosing method was validated. Then fludrocortisone acetate 10-µg capsules and 1% fludrocortisone acetate titrated powders (powder triturates) were realized. Finally, stability studies were performed. The fludrocortisone acetate titrated powders (powder triturates) were stable for one year at controlled ambient temperature and protected from light, whereas 10-µg fludrocortisone acetate capsules were stable for six months. One year after, even if the fludrocortisone content remained conformed, an increase in product degradation was noted. Our work allowed us to determine a six-month beyond-use date for fludrocortisone acetate titrated powder (powder triturate) with the three most commonly used excipients for capsule compounding. We also confirmed the sixmonth theoretical stability for capsules.