College of Pharmacy, University of Iowa, 115 S. Grand Avenue, Iowa City, IA 52242, USA.
Drug Product Development, Celgene, 556 Morris Avenue, Summit, NJ 07901, USA.
Int J Pharm. 2019 Sep 10;568:118509. doi: 10.1016/j.ijpharm.2019.118509. Epub 2019 Jul 10.
The objectives of this study were to evaluate the impact of formulation variables on the drying of nanocrystalline suspensions either via bead layering or spray granulation and develop mini-tablets from the dried nanocrystalline powders. Irbesartan (crystalline Form B), a poorly soluble drug substance was chosen as a model compound. An optimized irbesartan nanocrystalline suspension with a mean particle size of 300 nm was utilized for the downstream processing. Irbesartan nanocrystalline suspension was dried either by layering onto the microcrystalline cellulose beads (i.e. 200 or 500 µm) or by granulation (mannitol or microcrystalline cellulose as substrates) at two different drug loadings (i.e. 10% or 30% w/w). Smaller size beads layered with nanocrystals resulted in faster dissolution profiles compared to larger size beads at both the studied drug loadings (i.e. 10 and 30% w/w). Mannitol granules containing irbesartan nanocrystals resulted in faster dissolution profiles compared to microcrystalline cellulose granules. Microcrystalline cellulose beads and mannitol granules containing irbesartan nanocrystals (i.e. 30% w/w drug loading) were further compressed into mini-tablets. Mini-tablets retained fast drug dissolution characteristics of the dried powders. The results from this study indicated that the spray granulation is a superior drying approach compared to bead layering for drying of irbesartan nanocrystalline suspension and mini-tablet development.
本研究的目的是评估制剂变量对通过珠层或喷雾造粒干燥纳米晶混悬液的影响，并从干燥的纳米晶粉末中开发微型片剂。厄贝沙坦（晶型 B）是一种难溶性药物，被选为模型化合物。使用优化的平均粒径为 300nm 的厄贝沙坦纳米晶混悬液进行下游加工。将厄贝沙坦纳米晶混悬液分层到微晶纤维素珠（即 200 或 500µm）上或通过造粒（甘露醇或微晶纤维素作为基质）在两种不同的药物载量（即 10%或 30%w/w）下进行干燥。在研究的两种药物载量（即 10%和 30%w/w）下，与较大粒径的珠相比，较小粒径的珠层与纳米晶结合可导致更快的溶解曲线。含有厄贝沙坦纳米晶的甘露醇颗粒比含有厄贝沙坦纳米晶的微晶纤维素颗粒导致更快的溶解曲线。含有厄贝沙坦纳米晶的微晶纤维素珠（即 30%w/w 药物载量）和甘露醇颗粒进一步被压制成微型片剂。微型片剂保留了干燥粉末快速药物释放的特点。本研究结果表明，与珠层相比，喷雾造粒是一种更优越的干燥方法，适用于干燥厄贝沙坦纳米晶混悬液和开发微型片剂。
