难溶性药物的可再分散速溶纳米复合微粒
Redispersible fast dissolving nanocomposite microparticles of poorly water-soluble drugs.
作者信息
Bhakay Anagha, Azad Mohammad, Bilgili Ecevit, Dave Rajesh
机构信息
Otto H. York Department of Chemical, Biological and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, NJ, USA.
Otto H. York Department of Chemical, Biological and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, NJ, USA.
出版信息
Int J Pharm. 2014 Jan 30;461(1-2):367-79. doi: 10.1016/j.ijpharm.2013.11.059. Epub 2013 Dec 11.
Enhanced recovery/dissolution of two wet media-milled, poorly water-soluble drugs, Griseofulvin (GF) and Azodicarbonamide (AZD), incorporated into nanocomposite microparticles (NCMPs) via fluidized bed drying (FBD) and spray-drying (SD) was investigated. The effects of drying method, drug loading, drug aqueous solubility/wettability as well as synergistic stabilization of the milled suspensions on nanoparticle recovery/dissolution were examined. Drug nanoparticle recovery from FBD and SD produced NCMPs having high drug loadings was evaluated upon gentle redispersion via optical microscopy and laser diffraction. During wet-milling, hydroxypropyl cellulose (HPC) alone stabilized more wettable drug (AZD) nanoparticles with slight aggregation, but could not prevent aggregation of the GF nanoparticles. In contrast, well-dispersed, stable nanosuspensions of both drugs were produced when sodium dodecyl sulfate (SDS) and HPC were combined. The FBD and SD NCMPs without SDS exhibited incomplete nanoparticle recovery, causing slower dissolution for GF, but not for AZD, likely due to higher aqueous solubility/wettability of AZD. For high active loaded NCMPs (FBD ∼50 wt%, SD ∼80 wt%) of either drug, HPC-SDS together owing to their synergistic stabilization led to fast redispersibility/dissolution, corroborated via optical microscopy and particle sizing. These positive attributes can help development of smaller, high drug-loaded dosage forms having enhanced bioavailability and better patient compliance.
研究了通过流化床干燥(FBD)和喷雾干燥(SD)将两种经湿法介质研磨的难溶性药物灰黄霉素(GF)和偶氮二甲酰胺(AZD)掺入纳米复合微粒(NCMPs)中的增强回收/溶解情况。考察了干燥方法、药物负载量、药物的水溶性/润湿性以及研磨悬浮液的协同稳定作用对纳米颗粒回收/溶解的影响。通过光学显微镜和激光衍射对经温和再分散后从FBD和SD制备的具有高药物负载量的NCMPs中回收药物纳米颗粒的情况进行了评估。在湿法研磨过程中,单独使用羟丙基纤维素(HPC)可稳定更多具有轻微聚集的可湿性药物(AZD)纳米颗粒,但无法防止GF纳米颗粒的聚集。相比之下,当十二烷基硫酸钠(SDS)和HPC联合使用时,两种药物均能产生分散良好、稳定的纳米悬浮液。不含SDS的FBD和SD NCMPs表现出纳米颗粒回收不完全,导致GF的溶解较慢,但AZD不受影响,这可能是由于AZD具有较高的水溶性/润湿性。对于两种药物的高活性负载NCMPs(FBD约50 wt%,SD约80 wt%),由于HPC-SDS的协同稳定作用,通过光学显微镜和粒度分析证实其具有快速再分散性/溶解性。这些积极特性有助于开发具有更高生物利用度和更好患者顺应性的更小、高药物负载量的剂型。