World Health Organization (WHO) recommends the use of first-line anti-tuberculosis drugs, that is, rifampicin (RIF) and isoniazid (INH) fixed-dose combination (FDC) therapies in tuberculosis (TB) disease. The absorption of RIF from an FDC incorporates INH, and it is significantly compromised due to its reaction with INH, resulting in a severe loss of RIF under gastric stomach pH condition. Such reduction in the dose of both drugs from FDC formulations has been alleged to be one of the chief obstacles in effective TB treatment. This emphasizes a need to develop suitable cutting-edge advanced bioengineered delivery devices that can attenuate this severe problem to mitigate this chief obstacle. Therefore, we designed, prototyped, and characterized bioengineered 3D printed housing devices in the form of printed tablets adopting print and fill strategy for segregated compartmental delivery of RIF into the intestine (to avoid stomach gastric pH induced chemical degradation as alone and FDC) and INH into the stomach (no degradation observed as alone and FDC in stomach gastric pH conditions) for the desired treatment outcome against TB. Prepared 3D printed housings showed almost zero friability, enough hardness along weight variations <±3.0%. Different thermal and morphological analyses confirmed the insignificant changes in the nature of the polymer as before and after printing. The in vitro release for INH from polyvinyl alcohol mediated 3D printed housings showed almost 100% release within 2.5 h in acidic medium, whereas poly-lactic acid (PLA) mediated 3D printed housings continued to release RIF above 70% in the presence of physiological enzymes in alkaline medium for 432 h. The in vivo bioavailability assessment correlated with in vitro dissolution behavior for INH and RIF, whereas RIF did not release from 3D printed PLA housings in vivo.

中文翻译：

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采用打印和填充策略的 3D 打印外壳装置，用于口服固定剂量抗结核药物的隔离室输送


世界卫生组织（WHO）建议使用一线抗结核药物，即利福平（RIF）和异烟肼（INH）固定剂量联合用药（FDC）治疗结核病（TB）。 FDC中RIF的吸收含有INH，并且由于其与INH的反应而显着受损，导致RIF在胃pH条件下严重损失。 FDC 制剂中两种药物剂量的减少被认为是有效治疗结核病的主要障碍之一。这强调需要开发合适的尖端先进生物工程输送设备，以减轻这一严重问题，以减轻这一主要障碍。因此，我们以打印片剂的形式设计、原型化和表征了生物工程 3D 打印外壳装置，采用打印和填充策略将 RIF 隔离隔室递送到肠道中（以避免单独和 FDC 那样的胃胃 pH 引起的化学降解）和 INH进入胃中（在胃 pH 条件下，单独使用 FDC 和 FDC 时未观察到降解），以获得所需的结核病治疗结果。制备好的 3D 打印外壳的脆碎度几乎为零，并且重量变化具有足够的硬度 <±3.0%。不同的热分析和形态分析证实了打印前后聚合物性质的微小变化。聚乙烯醇介导的 3D 打印外壳的 INH体外释放显示，在酸性介质中 2.5 小时内几乎 100% 释放，而聚乳酸 (PLA) 介导的 3D 打印外壳在生理酶存在下继续释放 70% 以上的 RIF碱性介质中反应432 h。 体内生物利用度评估与 INH 和 RIF 的体外溶出行为相关，而 RIF在体内不会从 3D 打印的 PLA 外壳中释放。