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Fabrication of complex oral drug delivery forms by Three Dimensional Printing (tm)

机译:通过三维印刷(tm)制备复杂的口服给药形式

摘要

Three Dimensional Printing 3DPTM is a novel solid freeform fabrication technology that has been applied to the fabrication of complex pharmaceutical drug devices. Limitations of the technology as relating to pharmaceuticals have been addressed and prototype dosage forms have been fabricated. The resolution of the 3DP tablets was found to depend on particle size and liquid migration during printing and drying. The surface finish of 3DP tablets was enhanced by uniaxial pressing. Migration inhibiting additives were effective in limiting transport. Both aqueous and ethanol-based solutions showed a decrease in migration on the order of 20% when appropriate powder bed additives were introduced. Migration was also decreased by pre-printing barriers to confine secondary printed drug solutions. Low dosage forms were fabricated with as little as 2.3 nanograms. Lower dosages are expected upon dilution of the initial drug solution. Printing forms with high dosage is limited by powder void volume, filling efficiency, and drug solubility limits. Multiple print passes increased the dosage per tablet volume, 6, at the expense of process time. The use of drug suspensions to overcome solubility limits and uniaxial compression to reduce tablet volume was shown to significantly increase 6. The highest 8 achieved was 427 mg/cc for pressed suspension-printed tablets, representing 74% of the theoretical limit. Complex oral dosage forms were fabricated with 3DP to show lagged-release, extended-release, double-release, and zero-order-release. Release properties, such as lag time and release rate, were manipulated by varying the printing parameters.
机译:三维印刷3DPTM是一种新颖的固体自由形式制造技术,已被用于制造复杂的药物设备。已经解决了与药物有关的技术局限性,并制造了原型剂型。发现3DP片剂的分辨率取决于印刷和干燥过程中的粒径和液体迁移。通过单轴压制可增强3DP片剂的表面光洁度。抑制迁移的添加剂有效地限制了迁移。当引入适当的粉末床添加剂时,水性溶液和乙醇基溶液均显示出约20%的迁移减少。通过预印制屏障来限制次级印制药物溶液的迁移也得以减少。低剂量形式制备的低至2.3纳克。稀释初始药物溶液时,预期剂量较低。高剂量印刷形式受粉末空隙体积,填充效率和药物溶解度限制。多次打印通过增加了每片药片的剂量,即6片,但以处理时间为代价。药物混悬剂用于克服溶解度限制和单轴压缩以减少片剂体积的使用已显示出显着增加6。压制悬浮印刷片达到的最高8浓度为427 mg / cc,占理论极限的74%。用3DP制备了复杂的口服剂型,以显示出滞后释放,延长释放,双重释放和零级释放。释放特性(例如滞后时间和释放速率)通过更改打印参数进行控制。

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