• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

用于非晶态固体分散体原型制作的小型挤出机：热熔挤出增塑剂的选择

A Miniaturized Extruder to Prototype Amorphous Solid Dispersions: Selection of Plasticizers for Hot Melt Extrusion.

作者信息

Lauer Matthias E, Maurer Reto, Paepe Anne T De, Stillhart Cordula, Jacob Laurence, James Rajesh, Kojima Yuki, Rietmann Rene, Kissling Tom, van den Ende Joost A, Schwarz Sabine, Grassmann Olaf, Page Susanne

机构信息

Roche Pharmaceutical Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., CH-4070 Basel, Switzerland.

Pharmaceutical Research and Development, F. Hoffmann-La Roche Ltd., CH-4070 Basel, Switzerland.

出版信息

Pharmaceutics. 2018 May 19;10(2):58. doi: 10.3390/pharmaceutics10020058.

DOI:10.3390/pharmaceutics10020058
PMID:29783755
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6027370/
Abstract

Hot-melt extrusion is an option to fabricate amorphous solid dispersions and to enhance oral bioavailability of poorly soluble compounds. The selection of suitable polymer carriers and processing aids determines the dissolution, homogeneity and stability performance of this solid dosage form. A miniaturized extrusion device (MinEx) was developed and Hypromellose acetate succinate type L (HPMCAS-L) based extrudates containing the model drugs neurokinin-1 (NK1) and cholesterylester transfer protein (CETP) were manufactured, plasticizers were added and their impact on dissolution and solid-state properties were assessed. Similar mixtures were manufactured with a lab-scale extruder, for face to face comparison. The properties of MinEx extrudates widely translated to those manufactured with a lab-scale extruder. Plasticizers, Polyethyleneglycol 4000 (PEG4000) and Poloxamer 188, were homogenously distributed but decreased the storage stability of the extrudates. Stearic acid was found condensed in ultrathin nanoplatelets which did not impact the storage stability of the system. Depending on their distribution and physicochemical properties, plasticizers can modulate storage stability and dissolution performance of extrudates. MinEx is a valuable prototyping-screening method and enables rational selection of plasticizers in a time and material sparing manner. In eight out of eight cases the properties of the extrudates translated to products manufactured in lab-scale extrusion trials.

摘要

热熔挤出是制备无定形固体分散体和提高难溶性化合物口服生物利用度的一种方法。合适的聚合物载体和加工助剂的选择决定了这种固体剂型的溶出度、均匀性和稳定性。开发了一种小型挤出装置（MinEx），并制备了含有模型药物神经激肽-1（NK1）和胆固醇酯转移蛋白（CETP）的基于醋酸羟丙甲纤维素琥珀酸酯L型（HPMCAS-L）的挤出物，添加了增塑剂，并评估了它们对溶出度和固态性质的影响。用实验室规模的挤出机制造了类似的混合物，以便进行面对面比较。MinEx挤出物的性质与用实验室规模挤出机制造的挤出物的性质广泛相似。增塑剂聚乙二醇4000（PEG4000）和泊洛沙姆188均匀分布，但降低了挤出物的储存稳定性。发现硬脂酸凝聚成超薄纳米片，这对体系的储存稳定性没有影响。根据增塑剂的分布和物理化学性质，它们可以调节挤出物的储存稳定性和溶出性能。MinEx是一种有价值的原型筛选方法，能够以节省时间和材料的方式合理选择增塑剂。在所有八个案例中，挤出物的性质都与实验室规模挤出试验中制造的产品相似。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/980a/6027370/59f55e875ae7/pharmaceutics-10-00058-g015.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/980a/6027370/61bc5dd8a28a/pharmaceutics-10-00058-g0A1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/980a/6027370/4f1003026e5e/pharmaceutics-10-00058-g0A2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/980a/6027370/bad50b636356/pharmaceutics-10-00058-g0A3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/980a/6027370/cae9f82def32/pharmaceutics-10-00058-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/980a/6027370/7087f7978b4b/pharmaceutics-10-00058-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/980a/6027370/170442eea6af/pharmaceutics-10-00058-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/980a/6027370/0fd73fae7f2f/pharmaceutics-10-00058-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/980a/6027370/a88a60e0c39a/pharmaceutics-10-00058-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/980a/6027370/92481b5834c0/pharmaceutics-10-00058-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/980a/6027370/7c06debe3e1a/pharmaceutics-10-00058-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/980a/6027370/719fff3c2000/pharmaceutics-10-00058-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/980a/6027370/db89fd999d53/pharmaceutics-10-00058-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/980a/6027370/8eeaf1881a0e/pharmaceutics-10-00058-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/980a/6027370/7beb28f0da07/pharmaceutics-10-00058-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/980a/6027370/ccbfc8b502a0/pharmaceutics-10-00058-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/980a/6027370/ca05947cf1c4/pharmaceutics-10-00058-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/980a/6027370/e0ef16b15699/pharmaceutics-10-00058-g014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/980a/6027370/59f55e875ae7/pharmaceutics-10-00058-g015.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/980a/6027370/61bc5dd8a28a/pharmaceutics-10-00058-g0A1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/980a/6027370/4f1003026e5e/pharmaceutics-10-00058-g0A2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/980a/6027370/bad50b636356/pharmaceutics-10-00058-g0A3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/980a/6027370/cae9f82def32/pharmaceutics-10-00058-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/980a/6027370/7087f7978b4b/pharmaceutics-10-00058-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/980a/6027370/170442eea6af/pharmaceutics-10-00058-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/980a/6027370/0fd73fae7f2f/pharmaceutics-10-00058-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/980a/6027370/a88a60e0c39a/pharmaceutics-10-00058-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/980a/6027370/92481b5834c0/pharmaceutics-10-00058-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/980a/6027370/7c06debe3e1a/pharmaceutics-10-00058-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/980a/6027370/719fff3c2000/pharmaceutics-10-00058-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/980a/6027370/db89fd999d53/pharmaceutics-10-00058-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/980a/6027370/8eeaf1881a0e/pharmaceutics-10-00058-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/980a/6027370/7beb28f0da07/pharmaceutics-10-00058-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/980a/6027370/ccbfc8b502a0/pharmaceutics-10-00058-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/980a/6027370/ca05947cf1c4/pharmaceutics-10-00058-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/980a/6027370/e0ef16b15699/pharmaceutics-10-00058-g014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/980a/6027370/59f55e875ae7/pharmaceutics-10-00058-g015.jpg

相似文献

1
A Miniaturized Extruder to Prototype Amorphous Solid Dispersions: Selection of Plasticizers for Hot Melt Extrusion.用于非晶态固体分散体原型制作的小型挤出机：热熔挤出增塑剂的选择
Pharmaceutics. 2018 May 19;10(2):58. doi: 10.3390/pharmaceutics10020058.
2
Use of surfactants as plasticizers in preparing solid dispersions of poorly soluble API: stability testing of selected solid dispersions.在制备难溶性活性药物成分的固体分散体中使用表面活性剂作为增塑剂：所选固体分散体的稳定性测试
Pharm Res. 2006 Aug;23(8):1928-36. doi: 10.1007/s11095-006-9034-1.
3
Preparation of carbamazepine-Soluplus solid dispersions by hot-melt extrusion, and prediction of drug-polymer miscibility by thermodynamic model fitting.热熔挤出法制备卡马西平-Soluplus 固体分散体及热力学模型拟合预测药物-聚合物混合的相容性。
Eur J Pharm Biopharm. 2013 May;84(1):228-37. doi: 10.1016/j.ejpb.2012.12.018. Epub 2013 Jan 18.
4
Physicochemical characterization of hot melt extruded bicalutamide-polyvinylpyrrolidone solid dispersions.热熔挤出比卡鲁胺-聚乙烯吡咯烷酮固体分散体的理化性质表征。
J Pharm Sci. 2010 Mar;99(3):1322-35. doi: 10.1002/jps.21914.
5
Effects of Surfactants on Itraconazole-Hydroxypropyl Methylcellulose Acetate Succinate Solid Dispersion Prepared by Hot Melt Extrusion. II: Rheological Analysis and Extrudability Testing.表面活性剂对热熔挤出制备的伊曲康唑-羟丙甲纤维素醋酸琥珀酸酯固体分散体的影响。二：流变分析和可挤出性测试。
J Pharm Sci. 2019 Sep;108(9):3063-3073. doi: 10.1016/j.xphs.2019.05.010. Epub 2019 May 16.
6
Comparison of HPMC based polymers performance as carriers for manufacture of solid dispersions using the melt extruder.比较 HPMC 基聚合物作为热熔挤出法制备固体分散体载体的性能。
Int J Pharm. 2011 Oct 31;419(1-2):12-9. doi: 10.1016/j.ijpharm.2011.05.073. Epub 2011 Jul 22.
7
Effects of Surfactants on Itraconazole-Hydroxypropyl Methylcellulose Acetate Succinate Solid Dispersion Prepared by Hot Melt Extrusion III: Tableting of Extrudates and Drug Release From Tablets.热熔挤出制备的伊曲康唑-羟丙甲纤维素醋酸琥珀酸酯固体分散体中表面活性剂的影响 III：挤出物的压片和片剂的药物释放。
J Pharm Sci. 2019 Dec;108(12):3859-3869. doi: 10.1016/j.xphs.2019.09.014. Epub 2019 Sep 19.
8
Influence of methylparaben as a solid-state plasticizer on the physicochemical properties of Eudragit RS PO hot-melt extrudates.对羟基苯甲酸甲酯作为固态增塑剂对Eudragit RS PO热熔挤出物物理化学性质的影响。
Eur J Pharm Biopharm. 2003 Jul;56(1):95-100. doi: 10.1016/s0939-6411(03)00035-3.
9
Processing of Polyvinyl Acetate Phthalate in Hot-Melt Extrusion-Preparation of Amorphous Solid Dispersions.热熔挤出法制备聚醋酸乙烯邻苯二甲酸酯——无定形固体分散体的制备
Pharmaceutics. 2020 Apr 9;12(4):337. doi: 10.3390/pharmaceutics12040337.
10
Effect of composition in the development of carbamazepine hot-melt extruded solid dispersions by application of mixture experimental design.应用混合实验设计研究组成对卡马西平热熔挤出固体分散体形成的影响。
J Pharm Pharmacol. 2014 Feb;66(2):232-43. doi: 10.1111/jphp.12199. Epub 2013 Dec 18.

引用本文的文献

1
Cinnamon Essential Oil Delivery Systems: Preparation Processes, Packaging Forms, and Industrialization Potentials.肉桂精油递送系统：制备工艺、包装形式及产业化潜力
Food Sci Nutr. 2025 Aug 29;13(9):e70814. doi: 10.1002/fsn3.70814. eCollection 2025 Sep.
2
QbD-Based Development and Evaluation of Pazopanib Hydrochloride Extrudates Prepared by Hot-Melt Extrusion Technique: In Vitro and In Vivo Evaluation.基于质量源于设计的热熔挤出技术制备的盐酸帕唑帕尼挤出物的开发与评价：体外和体内评价
Pharmaceutics. 2024 Jun 4;16(6):764. doi: 10.3390/pharmaceutics16060764.
3
Material-Sparing Feasibility Screening for Hot Melt Extrusion.

本文引用的文献

1
Selection of Solid-State Plasticizers as Processing Aids for Hot-Melt Extrusion.固态增塑剂的选择作为热熔挤出加工助剂。
J Pharm Sci. 2018 Jan;107(1):372-379. doi: 10.1016/j.xphs.2017.09.004. Epub 2017 Sep 18.
2
Rheological Characterization of Molten Polymer-Drug Dispersions as a Predictive Tool for Pharmaceutical Hot-Melt Extrusion Processability.熔融聚合物-药物分散体的流变特性作为预测热熔挤出可加工性的工具。
Pharm Res. 2017 Nov;34(11):2312-2321. doi: 10.1007/s11095-017-2239-7. Epub 2017 Aug 15.
3
Statistical investigation of simulated fed intestinal media composition on the equilibrium solubility of oral drugs.
热熔挤出的材料节约可行性筛选
Pharmaceutics. 2024 Jan 5;16(1):76. doi: 10.3390/pharmaceutics16010076.
4
Vacuum Compression Molding as a Screening Tool to Investigate Carrier Suitability for Hot-Melt Extrusion Formulations.真空压缩成型作为一种筛选工具，用于研究载体对热熔挤出制剂的适用性。
Pharmaceutics. 2020 Oct 24;12(11):1019. doi: 10.3390/pharmaceutics12111019.
5
Pharmaceutical Applications of Hot-Melt Extrusion: Continuous Manufacturing, Twin-Screw Granulations, and 3D Printing.热熔挤出技术的药物应用：连续制造、双螺杆制粒及3D打印
Pharmaceutics. 2019 May 7;11(5):218. doi: 10.3390/pharmaceutics11050218.
6
Fast Dissolving of Ferulic Acid via Electrospun Ternary Amorphous Composites Produced by a Coaxial Process.通过同轴工艺制备的电纺三元非晶复合材料实现阿魏酸的快速溶解
Pharmaceutics. 2018 Aug 2;10(3):115. doi: 10.3390/pharmaceutics10030115.
模拟 fed 肠道介质组成对口服药物平衡溶解度的统计研究。 （注：这里“fed”可能是特定实验条件或状态的表述，具体含义需结合上下文确定，字面直译为“喂食的” ）
Eur J Pharm Sci. 2017 Mar 1;99:95-104. doi: 10.1016/j.ejps.2016.12.008. Epub 2016 Dec 7.
4
Bile Salt Micelles and Phospholipid Vesicles Present in Simulated and Human Intestinal Fluids: Structural Analysis by Flow Field-Flow Fractionation/Multiangle Laser Light Scattering.模拟和人体肠道液中存在的胆盐微团和磷脂囊泡：采用流场-流分级/多角度激光光散射进行结构分析
J Pharm Sci. 2016 Sep;105(9):2832-2839. doi: 10.1016/j.xphs.2016.03.005. Epub 2016 Apr 19.
5
Polymeric Amorphous Solid Dispersions: A Review of Amorphization, Crystallization, Stabilization, Solid-State Characterization, and Aqueous Solubilization of Biopharmaceutical Classification System Class II Drugs.聚合物无定形固体分散体：生物药剂学分类系统II类药物的非晶化、结晶、稳定化、固态表征及水相增溶综述
J Pharm Sci. 2016 Sep;105(9):2527-2544. doi: 10.1016/j.xphs.2015.10.008. Epub 2016 Jan 23.
6
Nanoscale Infrared, Thermal, and Mechanical Characterization of Telaprevir-Polymer Miscibility in Amorphous Solid Dispersions Prepared by Solvent Evaporation.通过溶剂蒸发制备的无定形固体分散体中替拉那韦与聚合物混溶性的纳米级红外、热学和力学表征
Mol Pharm. 2016 Mar 7;13(3):1123-36. doi: 10.1021/acs.molpharmaceut.5b00925. Epub 2016 Feb 24.
7
Spray drying formulation of amorphous solid dispersions.喷雾干燥法制备无定形固体分散体。
Adv Drug Deliv Rev. 2016 May 1;100:27-50. doi: 10.1016/j.addr.2015.12.010. Epub 2015 Dec 17.
8
Challenges and Strategies in Thermal Processing of Amorphous Solid Dispersions: A Review.非晶态固体分散体热加工中的挑战与策略：综述
AAPS PharmSciTech. 2016 Feb;17(1):43-55. doi: 10.1208/s12249-015-0393-y. Epub 2015 Aug 26.
9
Assessing Mixing Quality of a Copovidone-TPGS Hot Melt Extrusion Process with Atomic Force Microscopy and Differential Scanning Calorimetry.用原子力显微镜和差示扫描量热法评估共聚维酮-维生素E聚乙二醇1000琥珀酸酯热熔挤出工艺的混合质量
AAPS PharmSciTech. 2016 Feb;17(1):89-98. doi: 10.1208/s12249-015-0387-9. Epub 2015 Aug 18.
10
Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation.热熔挤出：从理论到药物制剂中的应用
AAPS PharmSciTech. 2016 Feb;17(1):20-42. doi: 10.1208/s12249-015-0360-7. Epub 2015 Jul 10.