3D打印技术在口服固体制剂中的应用研究进展

口服固体制剂是临床用药最为常见的剂型。3D打印技术能够通过计算机辅助设计精准调控口服固体制剂的内部构成以及外部形貌,进而控制药物释放性能,实现精准化治疗。近年来,国内外学者制备出了速释、缓控释、复方、中药等众多3D打印口服固体制剂,用于改善传统口服固体制剂存在的不足。随着精准化治疗的发展,3D打印药物制剂逐渐成为研究热点之一。同时,3D打印作为新兴科学技术存在些许不足,亟待科研工作者共同努力解决。本文综述3D打印技术分类及其在口服固体制剂中应用、机遇与挑战,为3D打印技术在口服固体制剂中的研究与应用提供参考依据,为临床个性化给药提供新的思路和技术。     

3D打印技术在口服固体制剂中的应用与挑战

近年来3D打印技术发展迅速,已被广泛应用于组织工程、牙科、建筑、汽车和航空航天等领域,然而在制药领域,该技术仍处于起步阶段,其潜力尚未得到充分发掘,直到FDA批准第一个3D打印药物才引起科研人员的兴趣。本文介绍了黏合剂沉积法、物料喷射法、挤出法、粉末床熔融法及光聚合法等各种3D打印技术,并尝试对目前使用3D打印技术制备的口服固体剂型(尤其是片剂)进行了全面回顾,突显其在制药领域较好的适用性。与传统制剂技术相比该技术具有明显的优势,其中最突出的是制剂个性化定制以提高依从性,但还需要克服诸多技术挑战,以释放其在制药工业中的真正潜力。     

3D打印制剂的研究进展和应用前景

随着精准医疗的发展,药物治疗领域也正从群体药物治疗向个体化药物治疗的方向发展。3D打印技术具有快速成型和数字化建模2个特点,在生产个体化、定制化药物制剂方面具有优势。随着3D打印技术的发展,越来越多的研究团队开始了3D打印制剂的研究。本文从3D打印制剂的剂型、质量控制、临床应用和3D打印技术4个方面综述近年来3D打印制剂的研究进展,并分析3D打印制剂的应用前景和面临的挑战。     

基于3D打印技术制备复方丹参缓控释制剂的研究

目的 使用3D打印技术制备复方丹参缓控释制剂,实现复方丹参制剂中特定组分在特定部位释放。方法 通过计算机辅助设计软件,设计多组分、双层级释放的药物三维数字模型,使用热熔挤出方式制备负载药物的打印丝材,使用熔融沉积3D打印方式制备复方丹参缓控释制剂,以及体外溶出试验初步测试制剂中药物释放情况。结果 使用3D打印技术成功制备复方丹参缓控释制剂,实现了药物组分中冰片仅在肠道中释放,而丹参和三七在胃肠道中均可释放的特性。结论 3D打印技术作为一种现代化科学技术,可用中药制剂现代化的研究。     

3D打印快速成型技术在泌尿外科领域中的应用进展

随着科学技术的发展,3D打印技术在医学领域的应用已成为近年来研究的热点,该文通过对3D打印原理与材料及其在泌尿外科领域的临床运用等方面进行综述,结合国内外文献资料总结其在泌尿外科领域的应用现状及对未来的展望.     

口服修饰释放制剂工艺的研究进展

通过制剂工艺技术比较，综述口服修饰释放系统的发展途径、剂型构成和基本成分。亲水骨架片是目前最常用的修饰释放系统。制剂工艺的发展要根据需要制定原则，考虑药物的性质结合剂型、生产的因素选择合理的释放系统。     

我院门诊口服钙制剂临床应用分析

目的评估口服钙制剂的临床应用情况。方法对医院2007年11月至2008年1月口服钙制剂的门诊处方进行统计分析。结果口服钙制剂的临床应用广泛,女性与中老年人使用尤多,补钙现象普遍。结论钙制剂有过度使用的趋势,补钙需谨慎。     

3D打印技术在膜剂制备中的研究进展

膜剂具有患者依从性好、携带及服药方便、剂量准确等特点。3D打印技术是基于计算机辅助设计模型的增材制造技术,一般通过分层打印、逐层叠加的方式构建物体,具有可提供复杂结构、制备复方制剂及个性化药物等优势。文章介绍了在膜剂制备中应用较广泛的喷墨打印、熔融沉积成型和半固体挤出技术,简要概述了3D打印膜剂的处方组成及关键工艺参数,以期为3D打印技术在膜剂领域的进一步应用和研究提供参考。     

Characterisation of fused deposition modeling 3D printers for pharmaceutical and medical applications

Abstract

Fused deposition modeling (FDM) is a promising 3D printing technique for the fabrication of personalized drug dosage forms and patient-specific implants. However, there are no market products produced by FDM available at this time. One of the reasons is the lack of a consistent and harmonized approval procedure. In this study, three FDM printers have been characterised with respect to printing parameters relevant for pharmaceutical and medical applications, namely the positioning, hot-end temperature, material residence time, printing velocity and volumetric material flow. The printers are the Ultimaker 2 (UM2), the PRotos v3 (PR3) as well as an in-house developed printer (IDP). The positioning results showed discrepancies between the printers, which are mainly based on different types of drive systems. Due to comparable utilised hot-ends and nozzle geometries, the results for the temperature and residence time distribution measurements were quite similar. The IDP has a high positioning accuracy but is limited with respect to printing velocity, while the achievable material volume flows were different for all printers. The presented characterisation method aims to contribute to the development of a harmonized equipment qualification framework for FDM printers, which could lead to an acceleration and facilitation of an approval procedure for 3D printed products.     

A flexible-dose dispenser for immediate and extended release 3D printed tablets

The advances in personalised medicine increased the demand for a fast, accurate and reliable production method of tablets that can be digitally controlled by healthcare staff. A flexible dose tablet system is presented in this study that proved to be suitable for immediate and extended release tablets with a realistic drug loading and an easy-to-swallow tablet design. The method bridges the affordable and digitally controlled Fused Deposition Modelling (FDM) 3D printing with a standard pharmaceutical manufacturing process, Hot Melt Extrusion (HME). The reported method was compatible with three methacrylic polymers (Eudragit RL, RS and E) as well as a cellulose-based one (hydroxypropyl cellulose, HPC SSL). The use of a HME based pharmaceutical filament preserved the linear relationship between the mass and printed volume and was utilized to digitally control the dose via an input from computer software with dose accuracy in the range of 91–95%. Higher resolution printing quality doubled the printing time, but showed a little effect on in vitro release pattern of theophylline and weight accuracy. Physical characterization studies indicated that the majority of the model drug (theophylline) in the 3D printed tablet exists in a crystal form. Owing to the small size, ease of use and the highly adjustable nature of FDM 3D printers, the method holds promise for future individualised treatment.     

Preparation and investigation of novel gastro-floating tablets with 3D extrusion-based printing

Three dimensional (3D) extrusion-based printing is a paste-based rapid prototyping process, which is capable of building complex 3D structures. The aim of this study was to explore the feasibility of 3D extrusion-based printing as a pharmaceutical manufacture technique for the fabrication of gastro-floating tablets. Novel low-density lattice internal structure gastro-floating tablets of dipyridamole were developed to prolong the gastric residence time in order to improve drug release rate and consequently, improve bioavailability and therapeutic efficacy. Excipients commonly employed in the pharmaceutical study could be efficiently applied in the room temperature 3D extrusion-based printing process. The tablets were designed with three kinds of infill percentage and prepared by hydroxypropyl methylcellulose (HPMC K4M) and hydroxypropyl methylcellulose (HPMC E15) as hydrophilic matrices and microcrystalline cellulose (MCC PH101) as extrusion molding agent. In vitro evaluation of the 3D printed gastro-floating tablets was performed by determining mechanical properties, content uniformity, and weight variation. Furthermore, re-floating ability, floating duration time, and drug release behavior were also evaluated. Dissolution profiles revealed the relationship between infill percentage and drug release behavior. The results of this study revealed the potential of 3D extrusion-based printing to fabricate gastro-floating tablets with more than 8 h floating process with traditional pharmaceutical excipients and lattice internal structure design.     

Formulation of 3D Printed Tablet for Rapid Drug Release by Fused Deposition Modeling: Screening Polymers for Drug Release,Drug-Polymer Miscibility and Printability

The primary aim of this study was to identify pharmaceutically acceptable amorphous polymers for producing 3D printed tablets of a model drug, haloperidol, for rapid release by fused deposition modeling. Filaments for 3D printing were prepared by hot melt extrusion at 150°C with 10% and 20% w/w of haloperidol using Kollidon^® VA64, Kollicoat^® IR, Affinsiol^?15 cP, and HPMCAS either individually or as binary blends (Kollidon^® VA64 + Affinisol^? 15 cP, 1:1; Kollidon^® VA64 + HPMCAS, 1:1). Dissolution of crushed extrudates was studied at pH 2 and 6.8, and formulations demonstrating rapid dissolution rates were then analyzed for drug-polymer, polymer-polymer and drug-polymer-polymer miscibility by film casting. Polymer-polymer (1:1) and drug-polymer-polymer (1:5:5 and 2:5:5) mixtures were found to be miscible. Tablets with 100% and 60% infill were printed using MakerBot printer at 210°C, and dissolution tests of tablets were conducted at pH 2 and 6.8. Extruded filaments of Kollidon^® VA64-Affinisol^? 15 cP mixtures were flexible and had optimum mechanical strength for 3D printing. Tablets containing 10% drug with 60% and 100% infill showed complete drug release at pH 2 in 45 and 120 min, respectively. Relatively high dissolution rates were also observed at pH 6.8. The 1:1-mixture of Kollidon^® VA64 and Affinisol^?15 cP was thus identified as a suitable polymer system for 3D printing and rapid drug release.     

3D打印华法林钠片的质量评价

目的：对不同剂量的3D打印华法林钠片进行质量评价。方法：采用HPLC法进行样品含量及有关物质测定,含量均匀度测定;采用质构仪测定片剂的硬度和崩解时间;采用《中国药典》方法将3D打印华法林钠片溶出时间与传统压片制剂比较;采用《欧洲药典》方法将3D打印分剂量方式与传统分劈分剂量方式进行比较;采用光学显微镜和相机观察3D打印片剂的内部结构和外观。结果：3D打印华法林钠片的各项指标均合格,且溶出时间较传统片剂快,分剂量方式也更准确简便。结论：3D打印技术可作为片剂分剂量的一种重要手段。     

Investigating cascade impactor performance using a modified 3D printed induction port

Based on a computer tomographic scan of a human trachea, a modified induction port (mIP), for use with the Next Generation Cascade Impactor, was manufactured using 3D printing technology. Standard United States Pharmacopoeia IP (USPIP) was compared to the mIP and a 3D printed version of the USPIP (USP3DIP) by analyzing different types of commercial salbutamol formulations for inhalation. Increased retention of particles in the mIP was found analyzing a pMDI formulation, leading to a decrease in the FPF from 28.8 ± 2.0% to 14.2 ± 1.2%, which correlates better to in vivo deposition data from literature. Increased deposition was found to be based on geometrical factors only. The impact of surface related effects was investigated by (a) comparing results obtained with the USPIP and USP3DIP (all formulations) and (b) generating another model IP (USP3DSEIP) with a surface area equivalent to the mIP but maintaining the geometry of the USPIP (pMDI only). USPIP, USP3DIP, and USP3DSEIP were found to perform equivalently. The impact of different geometries on airflow velocities in the USPIP and mIP was assessed using a computational fluid dynamics (CFD) model. Conclusively, this study shows that replacing the USP IP by the mIP can provide additional information in formulation assessment and in in vitro/in vivo correlation, when applied on pMDI formulations.     

口腔膜剂制备工艺的研究进展

作为一种新型便捷的口服给药方式,口腔膜剂有着众多优于传统口服给药方式的特点,使其受到国内外研究者和医药企业越来越多的关注。本文主要对口腔膜剂制备技术的发展进行综述,包括溶液浇铸法、热熔挤出法、静电纺丝技术和3D打印技术。     

3D printed tacrolimus suppositories for the treatment of ulcerative colitis

Ulcerative colitis is a global health problem,affecting millions of individuals worldwide.As an inflammatory condition localised in the large intestine,rectal d...     

Development of filaments for fused deposition modeling 3D printing with medical grade poly(lactic-co-glycolic acid) copolymers

The manufacturing of custom implants and patient-tailored drug dosage forms with fused deposition modeling (FDM) three-dimensional (3D) printing is currently considered to be very promising. Most FDM printers are designed as an open filament system, for which filaments with a defined size are required. In addition to this processing requirement, the filament material must be of medical or pharmaceutical quality, in order to be suitable in these applications. In this work, filaments with nominal diameters of 1.75?mm and diameter tolerances of ±0.05?mm or lower were developed in a continuous extrusion process. The filaments were made from different medical grade poly(lactic-co-glycolic acid) (PLGA) copolymers. Thermal characterization of the material with differential scanning calorimetry (DSC) showed increased material degradation with increasing hydrophilicity. Mechanical characterization of the filaments showed tensile strengths in the range of 41–48?MPa and Young’s moduli in the range of 2055–2099?MPa. Stress relaxation tests showed no irreversible change in filament diameter under processing conditions similar to the utilized 3D printer. Due to unexpected differences in processability in the 3D printer, the molecular weight of the materials was identified as an additional relevant parameter.