Wongmekiat Arpansiree, Tozuka Yuichi, Oguchi Toshio, Yamamoto Keiji
Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan.
Int J Pharm. 2003 Oct 20;265(1-2):85-93. doi: 10.1016/s0378-5173(03)00409-5.
The purpose of this study was to investigate the effect of moisture condition during cogrinding process on fine drug particle formation. Cogrinding of cyclodextrins (CDs) and pranlukast (PRK) hemihydrate was performed in various moisture conditions at a mixing molar ratio of 2:1 (CDs:PRK) and the formation of PRK submicron particle was investigated. The moisture content in the cogrinding process significantly affected the fine particle formation. More than 90% of pranlukast loaded transformed to submicron particles when coground with alpha-CD, beta-CD or gamma-CD containing the specific amount of water for each CD system. Fine particle formation of PRK was considered as a particular phenomenon to cyclodextrins, since the submicron particles could not be formed when D-mannitol, lactose or microcrystalline cellulose (MCC) was used as a cogrinding additive. Moreover, the appearance and disappearance of fine particle formation was found to be reversible depending on the existence of water during the grinding process.
本研究的目的是考察共研磨过程中的水分条件对药物细颗粒形成的影响。以2:1（环糊精：普仑司特）的混合摩尔比，在不同水分条件下对环糊精（CDs）与普仑司特（PRK）半水合物进行共研磨，并研究PRK亚微米颗粒的形成情况。共研磨过程中的水分含量对细颗粒的形成有显著影响。当与含有特定量水分的α-环糊精、β-环糊精或γ-环糊精共研磨时，超过90%负载的普仑司特转化为亚微米颗粒。PRK细颗粒的形成被认为是环糊精特有的现象，因为当使用D-甘露醇、乳糖或微晶纤维素（MCC）作为共研磨添加剂时，无法形成亚微米颗粒。此外，发现细颗粒形成的出现和消失取决于研磨过程中水分的存在，是可逆的。
