Bartos Csilla, Motzwickler-Németh Anett, Kovács Dávid, Burián Katalin, Ambrus Rita
Institute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, 6720 Szeged, Hungary.
Department of Medical Microbiology, Albert Szent-Györgyi Medical School, University of Szeged, 6720 Szeged, Hungary.
Pharmaceutics. 2024 Nov 25;16(12):1512. doi: 10.3390/pharmaceutics16121512.
This article reports on the scalability of a combined wet grinding technique applying planetary ball mill and ZrO pearls as the grinding medium. After the determination of the parameters in a laboratory scale, the tenfold scale-up method was set. Meloxicam (MEL) was used as a nonsteroidal anti-inflammatory drug (NSAID) intended for per os delivery. During grinding, the PVA solution was used as a dispersion medium. The influence of the scaling-up on the particle size, morphology, crystallinity, and intra- and interparticulate phenomena has been studied. Formulation investigations of the milled suspensions were carried out. The dissolution test and the cytotoxicity analyses were accomplished. Submicron MEL particle-containing samples were produced in both grinding scales. After the particle size determination was achieved from the suspensions, the wet milled, dried products were studied. The particle size of the dried products fell into the same range for both scales of milling (the maximum particle size was about 580 nm). There was no significant difference in drug crystallinity after the grindings; 70% of MEL remained crystalline in both cases. A remarkable interaction between the components did not develop as a result of milling. The polarity of the products increased, which resulted in a better dissolution, especially in the case of intestinal fluid (~100% in the first 5 min). The products were not found to be toxic. This research demonstrates that the scaling-up of combined wet grinding technique is feasible by adjusting the milling parameters and the adequate amount of excipient.
本文报道了一种采用行星球磨机和ZrO珠作为研磨介质的联合湿磨技术的可扩展性。在实验室规模确定参数后，设定了十倍放大方法。美洛昔康（MEL）用作口服给药的非甾体抗炎药（NSAID）。研磨过程中，使用聚乙烯醇（PVA）溶液作为分散介质。研究了放大对粒径、形态、结晶度以及颗粒内和颗粒间现象的影响。对研磨后的悬浮液进行了配方研究。完成了溶出度试验和细胞毒性分析。在两种研磨规模下均制备了含亚微米级MEL颗粒的样品。从悬浮液中测定粒径后，对湿磨干燥产品进行了研究。两种研磨规模下干燥产品的粒径范围相同（最大粒径约为580nm）。研磨后药物结晶度无显著差异；两种情况下70%的MEL仍为结晶态。研磨后各成分之间未产生明显相互作用。产品的极性增加，这导致溶出度提高，尤其是在肠液中（前5分钟约100%）。未发现产品有毒性。本研究表明，通过调整研磨参数和适量辅料，联合湿磨技术的放大是可行的。
