Purpose

We aimed to evaluate the feasibility of cross-linked polystyrene (CPS)–yttrium-stabilized zirconia (YSZ) bead mixtures as a novel optimization approach for fast, effective production of drug nanosuspensions during wet stirred media milling (WSMM).

Methods

Aqueous suspensions of 10% fenofibrate (FNB, drug), 7.5% HPC-L, and 0.05% SDS were wet-milled at 3000–4000 rpm and 35%–50% volumetric loading of CPS:YSZ bead mixtures (CPS:YSZ 0:1–1:0 v:v). Laser diffraction, SEM, viscometry, DSC, and XRPD were used for characterization. An n^th-order model described the breakage kinetics, while a microhydrodynamic model allowed us to gain insights into the impact of bead materials.

Results

CPS beads achieved the lowest specific power consumption, whereas YSZ beads led to the fastest breakage. Breakage followed second-order kinetics. Optimum conditions were identified as 3000 rpm and 50% loading of 0.5:0.5 v/v CPS:YSZ mixture from energy–cycle time–heat dissipation perspectives. The microhydrodynamic model suggests that YSZ beads experienced more energetic/forceful collisions with smaller contact area as compared with CPS beads owing to the higher density–elastic modulus of the former.

Conclusions

We demonstrated the feasibility of CPS–YSZ bead mixtures and rationalized its optimal use in WSMM through their modulation of breakage kinetics, energy utilization, and heat dissipation.

中文翻译：

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使用珠粒混合物作为药物悬浮液纳米研磨的新工艺优化方法

目的

我们旨在评估交联聚苯乙烯 (CPS)-钇稳定氧化锆 (YSZ) 珠粒混合物作为在湿搅拌介质研磨 (WSMM) 过程中快速、有效生产药物纳米悬浮液的新型优化方法的可行性。

方法

将 10% 非诺贝特（FNB，药物）、7.5% HPC-L 和 0.05% SDS 的水悬浮液以 3000–4000 rpm 和 35%–50% 体积负载的 CPS:YSZ 珠混合物（CPS:YSZ 0 :1–1:0 v:v)。使用激光衍射、SEM、粘度测定法、DSC 和 XRPD 进行表征。的n^个阶模型中描述的破损动力学，而microhydrodynamic模型使我们能够洞察珠材料的影响。

结果

CPS 磁珠的单位功耗最低，而 YSZ 磁珠的破损速度最快。破损遵循二级动力学。从能量-循环时间-散热的角度来看，最佳条件被确定为 3000 rpm 和 50% 负载的 0.5:0.5  v /v CPS:YSZ 混合物。微流体动力学模型表明，与 CPS 珠相比，YSZ 珠在较小的接触面积下经历了更多的能量/强力碰撞，因为前者具有更高的密度-弹性模量。

结论

我们证明了 CPS-YSZ 珠粒混合物的可行性，并通过其对破碎动力学、能量利用和散热的调节使其在 WSMM 中的最佳使用合理化。