Le Hoang Lan, Bouwhuis Natalja, Hollak Carla E M, Wilhelm Abraham J, Gerards Anne-Loes E, Bijleveld Yuma A, Swart Eleonora L
Department of Pharmacy and Clinical Pharmacology, Amsterdam UMC Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Medicine for Society, Platform at Amsterdam UMC Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Pharmaceutics. 2025 Mar 25;17(4):417. doi: 10.3390/pharmaceutics17040417.
: Ambroxol hydrochloride (AMB) is a promising chaperone for treating neurological manifestations in Gaucher disease type 3 (GD3). The Amsterdam University Medical Center planned to conduct an n-of-1 clinical trial using high-dose AMB (25 mg/kg/day). As an adequate commercial AMB formulation is unavailable for this high target dosage, we aimed to develop high-dose AMB capsules and assess the formulated capsule's quality. : AMB API was sourced and tested according to the requirements of the European Pharmacopoeia. Capsule formulations of 75 mg and 200 mg AMB were developed. Drug product specifications were set following international guidelines (ICH Q6A) and the European Pharmacopoeia. Analytical methods were developed and validated, and three validation batches of each capsule strength were produced and analyzed. : The contents and the Acceptance Values (AVs) of the initial AMB batches (both strengths) varied between 89.1% to 92.7% (specification: 90% to 110%) and 12.4 to 17.6 (specification ≤ 15.0), respectively, indicating non-uniform AMB distribution. Consequently, the production of 200 mg capsules was discontinued, and modifications were made to the 75 mg capsule formulation, followed by the production of three optimized 75 mg validation batches. These batches met the specified criteria, with an AMB content and AV values ranging from 93.9% to 96.5% and 12.4 to 14.9, respectively. Furthermore, rapid dissolution profiles were observed (>80% dissolution within 15 min). No degradation products or microbiological impurities were detected after production. : The optimized formulation of 75 mg AMB capsules formulated within the hospital pharmacy setting resulted in qualitative and uniform capsules which can be used in clinical trials.
盐酸氨溴索（AMB）是一种有前景的伴侣分子，用于治疗3型戈谢病（GD3）的神经学表现。阿姆斯特丹大学医学中心计划开展一项单病例临床试验，使用高剂量AMB（25毫克/千克/天）。由于没有适用于这一高目标剂量的市售AMB制剂，我们旨在研发高剂量AMB胶囊并评估所配制胶囊的质量。：按照欧洲药典的要求采购并检测了AMB原料药。研发了75毫克和200毫克AMB的胶囊制剂。依据国际指南（ICH Q6A）和欧洲药典制定了药品规格。开发并验证了分析方法，生产并分析了每种胶囊规格的三批验证批次产品。：初始AMB批次（两种规格）的含量和接受值（AVs）分别在89.1%至92.7%（规格：90%至110%）和12.4至17.6（规格≤15.0）之间变化，表明AMB分布不均匀。因此，停止了200毫克胶囊的生产，并对75毫克胶囊制剂进行了改进，随后生产了三批优化的75毫克验证批次产品。这些批次符合规定标准，AMB含量和AV值分别在93.9%至96.5%和12.4至14.9之间。此外，观察到快速溶出曲线（15分钟内溶出>80%）。生产后未检测到降解产物或微生物杂质。：在医院药房环境中配制的75毫克AMB胶囊的优化制剂产生了质量合格且均匀的胶囊，可用于临床试验。
