临时调配口服溶剂介质的制备及临床应用探索

Preparation and exploration of clinical applications of extemporaneous compounding oral pharmaceutical vehicles

摘要

目的: 研发适用于特殊人群分剂量给药的临时调配口服溶剂介质,验证其在临床分剂量给药中的应用可行性。方法: 基于原研产品分析与处方筛选优化,制备口服溶剂介质并对其关键质量属性与稳定性进行考察;随后,以螺内酯片为模型药物,考察药物在该介质中的溶解性、含量稳定性、分散均匀性,并对调配后制剂的适口性开展初步主观评价。结果: 所制备的口服溶剂介质在性状、pH值、相对密度、防腐剂含量及微生物限度等方面均符合既定标准,加速及长期条件下稳定性良好,货架期24个月便于医疗机构常规配备;调配后螺内酯混悬药液60 d内理化性质稳定,药物含量均保持在90%以上,分散均匀性良好(RSD=1.29%),口感主观评价显示其适口性有所改善。结论: 该口服溶剂介质在关键质量属性控制及体系稳定性方面具有良好的可控性,能够支持模型药物在分剂量调配过程中保持均匀分散与理化性质稳定,有望为特殊人群个体化分剂量给药提供可行方案。

Abstract

Objective: To develop an extemporaneous oral vehicle suitable for dose-splitting administration in special populations and to evaluate its clinical feasibility. Methods: Based on analysis of reference product and formulation screening, an oral vehicle was prepared and evaluated for critical quality attributes (CQAs) and stability. Using spironolactone tablets as a model drug, the solubility, content stability, and dispersion uniformity of the drug in the vehicle were investigated. A preliminary subjective assessment of palatability was also performed. Results: The prepared vehicle met the specifications for appearance, pH, relative density, preservative content, and microbial limits. It remained stable under accelerated and long-term storage conditions, enabling a 24-month shelf life for routine stocking in medical institutions. Spironolactone was uniformly dispersed in the vehicle and remained physicochemically stable for 60 days, with drug content maintained above 90% and a dispersion uniformity relative standard deviation (RSD=1.29%). Subjective palatability evaluation showed improved palatability. Conclusion: The developed oral vehicle demonstrates robust control of critical quality attributes and system stability, enabling the model drug to maintain uniform dispersion and physicochemical stability during dose-splitting compounding. It holds promise for providing a feasible approach for individualized dose-splitting administration in special populations.

关键词

临时调配 / 口服溶剂介质 / 特殊人群用药 / 个性化给药 / 螺内酯

Key words

extemporaneous compounding / oral pharmaceutical vehicle / special populations / split-dose administration / spironolactone

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