Shokraneh Farnaz, Filppula Anne M, Tornio Aleksi, Aruväli Jaan, Paaver Urve, Topelius Niklas Sandler
Pharmaceutical Sciences Laboratory, Science and Engineering, Åbo Akademi University, BioCity, Tykistökatu 6A, Turku FI-20520, Finland; CurifyLabs Oy, Salmisaarenaukio 1, Helsinki FI-00180, Finland.
Pharmaceutical Sciences Laboratory, Science and Engineering, Åbo Akademi University, BioCity, Tykistökatu 6A, Turku FI-20520, Finland.
Eur J Pharm Sci. 2025 Jan 1;204:106967. doi: 10.1016/j.ejps.2024.106967. Epub 2024 Nov 19.
The exploration of three-dimensional (3D) printing inspired technologies in pharmaceutical compounding reveals a promising frontier in personalized medicine manufacture. This study focuses on the development of clopidogrel bisulphate tablets, with doses ranging from 2 mg to 20 mg per tablet, suitable for pediatric use. The study explored a semi-solid extrusion-based deposition technology already being used in compounding pharmacies across several European locations. The investigation explored various properties of two formulations of 1 % and 2 % clopidogrel gel tablets, with a specific focus on mass variation, drug content uniformity, in vitro drug release profiles, disintegration time, and stability. The mean weights of the smallest printed 200 mg tablets with 1 % and 2 % clopidogrel concentrations were 199.1 ± 4.6 mg and 201.0 ± 3.2 mg, respectively. For the largest printed 500 mg tablets with 1 % and 2 % concentrations, the mean weights were 499.3 ± 7.7 mg and 501.7 ± 6.5 mg, respectively. The mean clopidogrel content uniformity for 1 % clopidogrel 200 mg and 500 mg tablets were 102.0 ± 1.8 %and 96.6 ± 2.6 %, respectively, and for 2 % clopidogrel 200 mg and 500 mg were 102.6 ± 3.9 % and 101.2 ± 1.6 %, respectively, well within the acceptable acceptance value (AV) range of 3 to 12. Both 1 % and 2 % formulations of clopidogrel tablets exhibited rapid drug release, meeting the USP pharmacopeial target of 85 % release in 15 min. All tablet sizes formulated at 1 % and 2 % concentrations met specified disintegration specifications. The stability assessment over three months revealed consistent pH values and assay results within target specifications for both clopidogrel formulations (93.5 % for 1 % formulation and 93.6 % for 2 % formulation). At three months, X-ray Diffraction (XRD) and Fourier Transform Infrared Spectroscopy (FTIR) results demonstrated stability in clopidogrel tablets. In conclusion, a comprehensive evaluation of our developed clopidogrel tablets demonstrate their suitability for clinical use in an extemporaneous setting using the presented semi-solid extrusion-based automation technology.
在药物配制中探索三维（3D）打印启发的技术，揭示了个性化药物制造中一个充满希望的前沿领域。本研究专注于开发硫酸氢氯吡格雷片，每片剂量范围为2毫克至20毫克，适用于儿科。该研究探索了一种基于半固体挤出的沉积技术，该技术已在欧洲多个地区的配药药房中使用。该调查研究了1%和2%氯吡格雷凝胶片两种制剂的各种特性，特别关注质量变化、药物含量均匀性、体外药物释放曲线、崩解时间和稳定性。1%和2%氯吡格雷浓度的最小打印200毫克片剂的平均重量分别为199.1±4.6毫克和201.0±3.2毫克。对于1%和2%浓度的最大打印500毫克片剂，平均重量分别为499.3±7.7毫克和501.7±6.5毫克。1%氯吡格雷200毫克和500毫克片剂的平均氯吡格雷含量均匀度分别为102.0±1.8%和96.6±2.6%，2%氯吡格雷200毫克和500毫克片剂的平均含量均匀度分别为102.6±3.9%和101.2±1.6%，均在3至12的可接受值（AV）范围内。1%和2%的氯吡格雷片制剂均表现出快速药物释放，符合美国药典在15分钟内释放85%的药典目标。所有1%和2%浓度配制的片剂尺寸均符合规定的崩解规格。三个月的稳定性评估显示，两种氯吡格雷制剂的pH值和含量测定结果在目标规格内一致（1%制剂为93.5%，2%制剂为93.6%）。在三个月时，X射线衍射（XRD）和傅里叶变换红外光谱（FTIR）结果证明氯吡格雷片具有稳定性。总之，对我们开发的氯吡格雷片进行的综合评估表明，使用所展示的基于半固体挤出的自动化技术，它们适用于临时配制环境中的临床使用。
