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线性和 4 臂星形聚(N-乙烯基吡咯烷酮)在个性化剂量片剂水基粘结剂喷射增材制造中的比较。

Comparison of Linear and 4-Arm Star Poly(vinyl pyrrolidone) for Aqueous Binder Jetting Additive Manufacturing of Personalized Dosage Tablets.

出版信息

ACS Appl Mater Interfaces. 2019 Jul 10;11(27):23938-23947. doi: 10.1021/acsami.9b08116. Epub 2019 Jun 25.

Abstract

Fabrication of personalized dosage oral pharmaceuticals using additive manufacturing (AM) provides patients with customizable, locally manufactured, and cost-efficient tablets, while reducing the probability of side effects. Binder jetting AM has potential for fabrication of customized dosage tablets, but the resulting products lack in strength due to solely relying on the binder to produce structural integrity. The selection of polymeric binders is also limited due to viscosity restraints, which limits molecular weight and concentration. To investigate and ameliorate these limitations, this article reports a comprehensive study of linear and 4-arm star poly(vinyl pyrrolidone) (PVP) over a range of molecular weights as polymeric binders for binder jetting AM and their effect on physical tablet properties. Formulation of varying molecular weights and concentrations of linear and 4-arm star PVP in deionized water and subsequent jetting revealed relationships between the critical overlap concentrations (*) and jettability on binder jetting systems with thermal inkjet printheads. After printing with a commercially available ZCorp Spectrum Z510 printer with an HP11 printhead with a lactose and powdered sugar powder bed, subsequent measurement of compressive strength, compressive modulus, and porosity revealed structure-property relationships between molecular weight, polymer concentration, and linear and 4-arm star architectures with physical properties of binder jetted tablets. This study elucidated that the dominating factor to increase compressive strength of a tablet is dependent on the weight percent of the polymer in the binder, which filled interstitial voids between powder particles. Because 4-arm star polymers have lower solution viscosities compared to linear analogues at the same molecular weights, they were jettable at higher concentrations, thus producing the strongest tablets at a compressive strength of 1.2 MPa. Finally, the inclusion of an active pharmaceutical ingredient (API), acetaminophen, revealed maintenance of the tablet physical properties across 5-50 total wt % API in each tablet.

摘要

使用增材制造(AM)制造个性化剂量的口服药物为患者提供了可定制、本地制造和具有成本效益的片剂,同时降低了副作用的可能性。粘结剂喷射 AM 具有制造定制剂量片剂的潜力,但由于仅依靠粘结剂来产生结构完整性,因此所得产品强度不足。由于粘度限制,粘结剂的选择也受到限制,这限制了分子量和浓度。为了研究和改善这些限制,本文报道了对线性和 4 臂星形聚(聚乙烯吡咯烷酮)(PVP)的综合研究,其分子量范围广泛,用作粘结剂喷射 AM 的粘结剂及其对物理片剂性质的影响。在去离子水中配制不同分子量和浓度的线性和 4 臂星形 PVP,并随后进行喷射,揭示了*临界缠结浓度与热喷墨打印头的粘结剂喷射系统的可喷射性之间的关系。在用市售的 ZCorp Spectrum Z510 打印机和带有乳糖和糖粉粉末床的 HP11 打印头打印后,随后测量压缩强度、压缩模量和孔隙率,揭示了分子量、聚合物浓度以及线性和 4 臂星形结构与粘结剂喷射片剂物理性质之间的结构-性质关系。该研究表明,增加片剂压缩强度的主要因素取决于粘结剂中聚合物的重量百分比,该百分比填充了粉末颗粒之间的空隙。由于 4 臂星形聚合物在相同分子量下的溶液粘度低于线性类似物,因此它们可以在更高的浓度下喷射,从而在压缩强度为 1.2 MPa 时产生最强的片剂。最后,包含活性药物成分(API)对乙酰氨基酚,结果表明在每个片剂中包含 5-50wt%的 API 时,片剂的物理性质保持不变。

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