Binson Guillaume, Beuzit Karine, Migeot Virginie, Marco Léa, Troussier Barbara, Venisse Nicolas, Dupuis Antoine
Health-Endocrine Disruptors-EXposome (HEDEX), CIC Inserm 1402, University Hospital of Poitiers, Poitiers 86021, France.
Department of Pharmacy, University Hospital of Poitiers, Poitiers 86021, France.
Pharmaceutics. 2019 Apr 18;11(4):190. doi: 10.3390/pharmaceutics11040190.
Dexamethasone, hydrochlorothiazide, spironolactone, and phenytoin are commonly used in neonates, but no age-appropriate formulation containing these active pharmaceutical ingredients (APIs) is commercially available. Thus, pharmaceutical compounding of the liquid oral dosage form is required to enable newborn administration. A problem common to the compounded preparations described in the literature is that they include potentially harmful excipients (PHEs). Therefore, the aim of this study was to evaluate the feasibility of compounding oral liquid dosage forms free of PHE, containing dexamethasone, hydrochlorothiazide, phenytoin, or spironolactone and to assess their physicochemical stability. Due to the poor water solubility of the targeted APIs, oral suspensions were compounded using Syrspend® SF-PH4 Dry, a suspending vehicle free of PHE. Four HPLC coupled to UV spectrometry (HPLC-UV) stability-indicating methods were developed and validated according to international guidelines to assay the strength of the targeted APIs. Whatever storage condition was used (5 ± 3 °C or 22 ± 4 °C), no significant degradation of API occurred in compounded oral suspensions. Overall, the results attest to the physical and chemical stability of the four oral liquid dosage forms over 60 days under regular storage temperatures. Finally, the use of the proposed oral suspensions provides a reliable solution to reduce the exposure of children to potentially harmful excipients.
地塞米松、氢氯噻嗪、螺内酯和苯妥英常用于新生儿，但目前尚无含有这些活性药物成分（API）且适合该年龄段的商业化制剂。因此，需要配制口服液体剂型以便新生儿服用。文献中描述的复方制剂普遍存在的一个问题是它们含有潜在有害辅料（PHE）。因此，本研究的目的是评估配制不含PHE的地塞米松、氢氯噻嗪、苯妥英或螺内酯口服液体剂型的可行性，并评估其物理化学稳定性。由于目标API的水溶性较差，使用不含PHE的混悬剂载体Syrspend® SF-PH4 Dry配制口服混悬剂。根据国际指南开发并验证了四种与紫外光谱联用的高效液相色谱（HPLC-UV）稳定性指示方法，以测定目标API的含量。无论采用何种储存条件（5±3℃或22±4℃），复方口服混悬剂中的API均未发生明显降解。总体而言，结果证明了这四种口服液体剂型在常规储存温度下60天内的物理和化学稳定性。最后，使用所建议的口服混悬剂为减少儿童接触潜在有害辅料提供了可靠的解决方案。
