The conventional “top-down”, “bottom-up” and “combination” approaches of generating drug nanocrystals produce a “nanosuspension” (NS). It requires significant downstream processing for drying the liquid by suitable means followed by its granulation to develop an oral solid dosage form (OSD). In this paper, we used a novel, spray drying-based NanoCrySP technology for the generation of drug nanocrystals in the form of nanocrystalline solid dispersion (NCSD). We hypothesized that the NCSD would require minimal downstream processing since the nanocrystals are obtained in powder form during spray drying. We further compared downstream processing of NS and NCSD of diclofenac acid (DCF) prepared by wet media milling and NanoCrySP technology, respectively. The NS and NCSD were characterized for crystallinity, crystal size, assay and dissolution. The NCSD was physically mixed with 0.3% Aerosil^® 200, 1.76% croscarmellose sodium (CCS) and 0.4% sodium stearyl fumarate (SSF) and filled into size 0 hard gelatin capsules. The NS was first wet granulated using Pearlitol^® SD 200 (G1 granules) and Celphere^® 203 (G2 granules) in a fluidized bed processor, and the resulting granules were mixed using the same extra granular excipients as NCSD and filled into capsules. A discriminatory dissolution method was developed to monitor changes in dissolution behavior due to crystal growth during processing. Cost analysis and comparison of process efficiency was performed using an innovation radar tool. The NS and NCSD were successfully fabricated with a crystal size of 363 ± 21.87 and 361.61 ± 11.78, respectively. In comparison to NCSD-based capsules (65.13%), the G1 and G2 granules showed crystal growth and decrease in dissolution to 52.68% and 48.37%, respectively, in 120 min. The overall cost for downstream processing of NCSD was up to 80% lower than that of NS. An innovation radar tool also concluded that the one-step NanoCrySP technology was more efficient and required less downstream processing than the two-step wet media milling approach for conversion of nanocrystals to OSD.

中文翻译：

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双氯芬酸纳米晶固体分散体和纳米悬浮液下游加工形成固体口服剂型的比较

产生药物纳米晶体的常规“自上而下”，“自下而上”和“组合”的方法会产生“纳米悬浮液”（NS）。它需要大量的下游处理，以通过合适的方式干燥液体，然后对其进行制粒以形成口服固体剂型（OSD）。在本文中，我们使用了一种基于喷雾干燥的新型NanoCrySP技术，以纳米晶体固体分散体（NCSD）的形式生成药物纳米晶体。我们假设NCSD将需要最少的下游处理，因为纳米晶体是在喷雾干燥过程中以粉末形式获得的。我们进一步比较了分别通过湿介质研磨和NanoCrySP技术制备的双氯芬酸（DCF）的NS和NCSD的下游加工。对NS和NCSD的结晶度，晶体大小，测定和溶解进行了表征。^® 200，1.76％羧甲基纤维素钠（CCS）和0.4％硬脂酰富马酸钠（SSF），并装入0号硬明胶胶囊中。的NS被第一湿使用的Pearlitol造粒^® SD 200（G1颗粒）和CELPHERE ^®203（G2颗粒）在流化床处理器中，并使用与NCSD相同的额外颗粒赋形剂混合所得颗粒，并装入胶囊中。开发了一种区分溶解方法，以监测由于加工过程中晶体生长引起的溶解行为变化。使用创新雷达工具进行了成本分析和过程效率比较。成功制造了NS和NCSD，晶体尺寸分别为363±21.87和361.61±11.78。与基于NCSD的胶囊（65.13％）相比，G1和G2颗粒在120分钟内显示出晶体生长，溶出度分别降至52.68％和48.37％。NCSD的下游处理总成本比NS低80％。