Investigation of Drug Nanoparticle Formation by Co-grinding with Cyclodextrins: Studies for Indomethacin, Furosemide and Naproxen
Investigation of Drug Nanoparticle Formation by Co-grinding with Cyclodextrins: Studies for Indomethacin, Furosemide and Naproxen
复制标题
DOI：
10.1007/s10847-006-9056-7
复制
发表时间：
2006-04
影响因子：
2.3
通讯作者：
A. Wongmekiat;Satoko Yoshimatsu;Y. Tozuka;K. Moribe;Keiji. Yamamoto
中科院分区：
文献类型：
--
作者：
A. Wongmekiat;Satoko Yoshimatsu;Y. Tozuka;K. Moribe;Keiji. Yamamoto
将水溶性差的药物与环糊精（CD）共研磨，以产生具有改善的溶解度特性的纳米颗粒。吲哚美辛（IDM）、呋塞米（FRM）和萘哌酚（NAP）与β-CD以2：1（CD：药物）的摩尔比共研磨。药物与CD的共研磨不仅导致药物纳米颗粒的形成，而且导致药物通过与CD在水性介质中形成包合络合物而增溶。用β-CD制备的研磨混合物中IDM和FRM的纳米颗粒分数高达60-70%，而增溶分数小于10%。相比之下，β-CD-NAP研磨混合物显示大部分（48%）用于药物增溶，而仅4%用于纳米颗粒形成。用α-CD、β-CD和γ-CD制备的呋塞米研磨混合物显示出相对高的纳米颗粒分数，而增溶分数约为10%。IDM-β-CD体系中的纳米颗粒分数和增溶分数均大于γ-CD和α-CD体系。NAP的纳米颗粒形成取决于用作共研磨添加剂的CD的类型。NAP与α-CD共研磨可制备纳米粒，β-CD或γ-CD共研磨可提高NAP的增溶作用。
Drugs with poor water solubility were co-ground with cyclodextrins (CDs) to create nanoparticles with improved solubility characteristics. Indomethacin (IDM), furosemide (FRM) and naproxen (NAP) were co-ground with β-CD at the molar ratio of 2:1 (CD:drug). Co-grinding of a drug with CD resulted in not only the formation of drug nanoparticles but also the solubilization of the drug by inclusion complex formation with CD in aqueous media. The nanoparticle fraction of IDM, and FRM from ground mixtures prepared with β-CD was as high as 60–70% while the solubilization fraction was less than 10%. In contrast, β-CD–NAP ground mixture showed a large fraction, 48%, for drug solubilization and only 4% for nanoparticle formation. Furosemide ground mixtures prepared with α-CD, β-CD and γ-CD showed comparatively high nanoparticle fraction while the solubilization fraction was around 10%. Both the nanoparticle fraction and the solubilization fraction were greater in the IDM–β-CD system than those in γ-CD and α-CD systems. The nanoparticle formation of NAP depended on the types of CD used as a co-grinding additive. Naproxen nanoparticles could be prepared by co-grinding NAP and α-CD, while the solubilization of NAP tended to improve when β-CD or γ-CD was used.