通过熔融挤出技术与熔融沉积制造 3D 打印相结合制造掩味甜甜圈形片剂。

Fabrication of Taste-Masked Donut-Shaped Tablets Via Fused Filament Fabrication 3D Printing Paired with Hot-Melt Extrusion Techniques.

机构信息

Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, Mississippi, 38677, USA.

Ashland Specialty Ingredients, Wilmington, Delaware, 19808, USA.

出版信息

AAPS PharmSciTech. 2020 Aug 27;21(7):243. doi: 10.1208/s12249-020-01783-0.

Abstract

The objective of this work was to develop taste-masked donut-shaped tablet formulations utilizing fused filament fabrication three-dimensional printing paired with hot-melt extrusion techniques. Caffeine citrate was used as the model drug for its bitter taste, and a 3-point bend test was performed to assess the printability of filaments. The stiffness constant was calculated to represent the printability by fitting the breaking distances and stress data into Hooke's law. The formulations without Eudragit E PO (F6) and with Eudragit E PO (F7) filaments exhibited the desired hardness with a "k" value of 48.30 ± 3.52 and 45.47 ± 3.51 g/mm (n = 10), respectively, and were successfully printed. The donut-shaped tablets were 3D printed with 10, 50, and 100% infill densities. In vitro dissolution studies were performed in simulated salivary fluid (pH 6.8, artificial saliva) to evaluate the taste-masking efficiency of the printed donuts. In the first minute, the concentrations of caffeine citrate observed in the dissolution media from all the printed donuts were less than the bitter threshold of caffeine citrate (0.25 mg/mL). Formulation F7, which contained Eudragit E PO copolymer, demonstrated better taste-masking efficiency than formulation F6. Furthermore, both formulations F6 and F7 demonstrated immediate drug release profiles in gastric medium (10% infill, > 80% release within 1 h). Taste-masked caffeine citrate formulations were successfully developed with donut shapes, which will enhance appeal in pediatric populations and increase compliance and patient acceptance of the dosage form.

摘要

这项工作的目的是开发利用熔融挤出技术与熔丝制造三维打印相结合的掩味甜甜圈形状片剂制剂。柠檬酸咖啡因被用作模型药物,因为它具有苦味,并且进行了 3 点弯曲测试来评估细丝的可打印性。通过将断裂距离和应力数据拟合到胡克定律中,计算出刚度常数来表示可打印性。没有 Eudragit E PO(F6)的配方和含有 Eudragit E PO(F7)的配方的细丝表现出所需的硬度,“k”值分别为 48.30±3.52 和 45.47±3.51 g/mm(n=10),并且可以成功打印。甜甜圈形状的片剂是用 10%、50%和 100%的填充密度进行 3D 打印的。在模拟唾液液(pH 6.8,人工唾液)中进行了体外溶解研究,以评估打印甜甜圈的掩味效率。在最初的一分钟内,从所有打印甜甜圈的溶解介质中观察到的柠檬酸咖啡因的浓度均低于柠檬酸咖啡因的苦味阈值(0.25 mg/mL)。含有 Eudragit E PO 共聚物的配方 F7 比配方 F6 具有更好的掩味效率。此外,两种配方 F6 和 F7 在胃介质中均表现出即刻药物释放曲线(10%填充,在 1 小时内释放超过 80%)。成功开发了具有甜甜圈形状的掩味柠檬酸咖啡因配方,这将提高儿科人群的吸引力,并提高顺应性和患者对剂型的接受度。

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