Azad Mohammad, Arteaga Colby, Abdelmalek Beshoy, Davé Rajesh, Bilgili Ecevit
a Otto H. York Department of Chemical , Biological and Pharmaceutical Engineering, New Jersey Institute of Technology , Newark , NJ , USA.
Drug Dev Ind Pharm. 2015;41(10):1617-31. doi: 10.3109/03639045.2014.976574. Epub 2014 Oct 27.
Bioavailability of a poorly soluble drug can be improved by preparing a drug nanosuspension and subsequently drying it into nanocomposite microparticles (NCMPs). Unfortunately, drug nanoparticles aggregate during milling and drying, causing incomplete recovery and slow dissolution. The aim of this study is to investigate the impact of various classes of dispersants on drug dissolution from drug NCMPs, with the ultimate goal of enhancing the bioavailability of poorly water-soluble drugs via high drug nanoparticle loaded, surfactant-free NCMPs. Precursor suspensions of griseofulvin (GF, model drug) nanoparticles in the presence of various dispersants were prepared via wet stirred media milling and spray dried to form the NCMPs. Hydroxypropyl cellulose (HPC, polymer) alone and with sodium dodecyl sulfate (SDS, surfactant) was used as a base-line stabilizer/dispersant during milling. Two swellable crosslinked polymers, croscarmellose sodium (CCS) and sodium starch glycolate (SSG), and a conventional soluble matrix former, Mannitol, were used in addition to HPC. Besides being used as-received, CCS was also wet co-milled with GF for two different durations to examine the impact of CCS particle size. Laser diffraction, scanning electron microscopy, powder X-ray diffraction (XRD), UV spectroscopy, NCMP redispersion and dissolution tests were used for characterization. The results show that incorporation of CCS/SSG, preferably wet-milled to a wide particle size distribution, into the spray-dried NCMPs resulted in fast release and dispersion of drug nanoparticle clusters. The swellable dispersants were superior to Mannitol in dissolution enhancement, and could achieve fast release comparable to SDS, demonstrating the feasibility of spray drying to prepare high drug-loaded, surfactant-free nanocomposites.
通过制备药物纳米混悬液并随后将其干燥成纳米复合微粒(NCMPs),可以提高难溶性药物的生物利用度。不幸的是,药物纳米颗粒在研磨和干燥过程中会聚集,导致回收率不完全和溶解缓慢。本研究的目的是研究各类分散剂对药物从药物NCMPs中溶解的影响,最终目标是通过高载药、无表面活性剂的NCMPs提高难溶性药物的生物利用度。在各种分散剂存在下,通过湿搅拌介质研磨制备灰黄霉素(GF,模型药物)纳米颗粒的前体混悬液,并喷雾干燥以形成NCMPs。在研磨过程中,单独使用羟丙基纤维素(HPC,聚合物)以及与十二烷基硫酸钠(SDS,表面活性剂)一起用作基线稳定剂/分散剂。除了HPC之外,还使用了两种可膨胀的交联聚合物,交联羧甲基纤维素钠(CCS)和淀粉乙醇酸钠(SSG),以及一种传统的可溶性成膜剂甘露醇。除了原样使用外,CCS还与GF湿共研磨两个不同的时间,以检查CCS粒径的影响。使用激光衍射、扫描电子显微镜、粉末X射线衍射(XRD)、紫外光谱、NCMP再分散和溶解试验进行表征。结果表明,将CCS/SSG(优选湿磨成宽粒径分布)掺入喷雾干燥的NCMPs中可导致药物纳米颗粒簇的快速释放和分散。可膨胀分散剂在溶解增强方面优于甘露醇,并且可以实现与SDS相当的快速释放,证明了喷雾干燥制备高载药、无表面活性剂纳米复合材料的可行性。
Eur J Pharm Biopharm. 2019-10-14