3PC-018 Poorly water-soluble drugs: is the compounding of adapted doses better than pharmaceutical marketed specialties? Example of diazoxide

<h3>Background and Importance</h3> Diazoxide is a first-line treatment for hyperinsulinemic hypoglycaemia in children.¹ While a 50 mg/mL oral suspension (Proglycem) is available through compassionate use, its high concentration and numerous excipients make it unsuitable for premature infants. In the neonatology department, diazoxide 25 mg capsules (Proglicem) are opened and dissolved in 5 mL of water. A specific volume, calculated based on the child’s weight, is then drawn with a syringe and administered. However, diazoxide is almost insoluble in water,² which raises concerns about its effectiveness in this preparation. <h3>Aim and Objectives</h3> The main objective was to measure the quantity administered to the patient by applying the service protocol. Possible alternatives to optimise the therapeutic management and secure the dose administered were also studied. <h3>Material and Methods</h3> The analysis and quantification of diazoxide in solution were conducted using UV spectrophotometry (λ = 280 nm). As this assay method was already routinely used in the control laboratory, the analytical validation criteria – linearity, accuracy, precision, and specificity – had been previously verified. The assays were performed using 25 mg capsules (Proglicem). The results were compared with a similar protocol using 5 mg capsules, prepared in-house as part of hospital formulations. Additionally, multiple rinses of the container were carried out to ensure the full recovery of the dissolved dose, aiming to optimise the administration process. <h3>Results</h3> After an adapted dilution in sodium hydroxide 0.1 M, the expected theoretical concentration of diazoxide was 10 µg/mL. The average concentrations (C̄) obtained from the dissolution tests (n=5) were as follows: 25 mg capsule (in 5 mL of water): C̄ = 5.64 µg/mL (± 0.93 µg/mL). 5 mg capsule (in 5 mL of water): C̄ = 6.87 µg/mL (± 0.29 µg/mL). 5 mg capsule (with successive rinses using 2+2+1 mL of water): C̄ = 7.06 µg/mL (± 0.098 µg/mL). The Student’s t-test comparing the average concentrations obtained through the different processes showed no significant difference at a 5% significance level. <h3>Conclusion and Relevance</h3> These trials highlight variability in current administration methods, with significant risks of under-dosing. The use of appropriately dosed capsules avoids dilution, improving the security of the administered dose. However, developing ready-to-use oral suspension could improve dosing accuracy and security. <h3>References and/or Acknowledgements</h3> https://base-donnees-publique.medicaments.gouv.fr/affichageDoc.php?specid=62678246&amp;typedoc=R https://go.drugbank.com/drugs/DB01119 <h3>Conflict of Interest</h3> No conflict of interest