Sadia Muzna, Sośnicka Agata, Arafat Basel, Isreb Abdullah, Ahmed Waqar, Kelarakis Antonios, Alhnan Mohamed A
School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, Lancashire, UK.
School of Medicine, University of Central Lancashire, Preston, Lancashire, UK.
Int J Pharm. 2016 Nov 20;513(1-2):659-668. doi: 10.1016/j.ijpharm.2016.09.050. Epub 2016 Sep 15.
This work aims to employ fused deposition modelling 3D printing to fabricate immediate release pharmaceutical tablets with several model drugs. It investigates the addition of non-melting filler to methacrylic matrix to facilitate FDM 3D printing and explore the impact of (i) the nature of filler, (ii) compatibility with the gears of the 3D printer and iii) polymer: filler ratio on the 3D printing process. Amongst the investigated fillers in this work, directly compressible lactose, spray-dried lactose and microcrystalline cellulose showed a level of degradation at 135°C whilst talc and TCP allowed consistent flow of the filament and a successful 3D printing of the tablet. A specially developed universal filament based on pharmaceutically approved methacrylic polymer (Eudragit EPO) and thermally stable filler, TCP (tribasic calcium phosphate) was optimised. Four model drugs with different physicochemical properties were included into ready-to-use mechanically stable tablets with immediate release properties. Following the two thermal processes (hot melt extrusion (HME) and fused deposition modelling (FDM) 3D printing), drug contents were 94.22%, 88.53%, 96.51% and 93.04% for 5-ASA, captopril, theophylline and prednisolone respectively. XRPD indicated that a fraction of 5-ASA, theophylline and prednisolone remained crystalline whilst captopril was in amorphous form. By combining the advantages of thermally stable pharmaceutically approved polymers and fillers, this unique approach provides a low cost production method for on demand manufacturing of individualised dosage forms.
这项工作旨在采用熔融沉积建模3D打印技术来制造含有几种模型药物的速释药物片剂。它研究了向甲基丙烯酸基质中添加非熔融填料以促进FDM 3D打印,并探讨了(i)填料的性质、(ii)与3D打印机齿轮的兼容性以及(iii)聚合物与填料的比例对3D打印过程的影响。在这项工作中研究的填料中,可直接压片的乳糖、喷雾干燥乳糖和微晶纤维素在135°C时出现一定程度的降解,而滑石粉和磷酸三钙(TCP)能使长丝持续流动,并成功实现片剂的3D打印。一种基于药学上批准的甲基丙烯酸聚合物(尤特奇EPO)和热稳定填料TCP(磷酸三钙)特别开发的通用长丝得到了优化。将四种具有不同物理化学性质的模型药物制成具有速释特性且机械稳定的即用型片剂。经过热熔挤出(HME)和熔融沉积建模(FDM)3D打印这两个热过程后,5-氨基水杨酸、卡托普利、茶碱和泼尼松龙的药物含量分别为94.22%、88.53%、96.51%和93.04%。X射线粉末衍射(XRPD)表明,5-氨基水杨酸、茶碱和泼尼松龙的一部分仍为结晶态,而卡托普利为无定形。通过结合热稳定的药学上批准的聚合物和填料的优点,这种独特的方法为按需制造个性化剂型提供了一种低成本的生产方法。