Evaluating the Effects of Crystallinity on Drug Release Behaviour in Itraconazole- or Miconazole-Loaded PLGA Microparticles Prepared Using a Co-Grinding Method  

作　　者：Kazuhiro Matsuura Honami Kojima Miyako Yoshida Takahiro Uchida Kazuhiro Matsuura;Honami Kojima;Miyako Yoshida;Takahiro Uchida(Formulation Technology Research Laboratories, Daiichi Sankyo Co., Ltd., Hiratsuka, Japan;Faculty of Pharmaceutical Science, Mukogawa Women’s University, Nishinomiya, Japan)

机构地区：[1]Formulation Technology Research Laboratories, Daiichi Sankyo Co., Ltd., Hiratsuka, Japan [2]Faculty of Pharmaceutical Science, Mukogawa Women’s University, Nishinomiya, Japan

出　　处：《Pharmacology & Pharmacy》2023年第9期348-362,共15页药理与制药（英文）

摘　　要：This study aimed to prepare and characterize itraconazole (ITCZ)- or miconazole (MCZ)-loaded poly (lactide-co-glycolide) (PLGA) microparticles (MP) using a co-grinding method with ball milling, which is a solvent-free and convenient procedure. PLGA MP was prepared by grinding for 60 min, and the fixed theoretical drug loading was set at 9.1% and 16.7% for both drugs. The obtained loading efficiency for both drugs was estimated to be approximately 100%. The average diameters of the drug-loaded PLGA MP were approximately 20 - 35 μm. Powder X-ray diffraction (PXRD) or differential scanning calorimetry (DSC) confirmed amorphization of ITCZ and MCZ in ITCZ- or MCZ-loaded PLGA MP in all formulations. The drug release percentage from 9.1%-loaded ITCZ-PLGA7505 MP at 24 h was almost 50%, which was higher than that of ITCZ powder. The drug release percentage from MCZ-loaded PLGA7505 MP at 4 h was over 80%, which was higher than that of MCZ powder. This enhancement of release rate is caused by the amorphization of ITCZ or MCZ in the PLGA matrix. MCZ-loaded PLGA7510 MP showed a sustained release profile up to 24 h, suggesting that MCZ exists in an amorphous form in the PLGA matrix;however, the release rate declined owing to the large molecular weight of PLGA. Therefore, the release enhancement of antifungal drugs loaded on PLGA MP could be achieved by their amorphization using a co-grinding method with ball milling.This study aimed to prepare and characterize itraconazole (ITCZ)- or miconazole (MCZ)-loaded poly (lactide-co-glycolide) (PLGA) microparticles (MP) using a co-grinding method with ball milling, which is a solvent-free and convenient procedure. PLGA MP was prepared by grinding for 60 min, and the fixed theoretical drug loading was set at 9.1% and 16.7% for both drugs. The obtained loading efficiency for both drugs was estimated to be approximately 100%. The average diameters of the drug-loaded PLGA MP were approximately 20 - 35 μm. Powder X-ray diffraction (PXRD) or differential scanning calorimetry (DSC) confirmed amorphization of ITCZ and MCZ in ITCZ- or MCZ-loaded PLGA MP in all formulations. The drug release percentage from 9.1%-loaded ITCZ-PLGA7505 MP at 24 h was almost 50%, which was higher than that of ITCZ powder. The drug release percentage from MCZ-loaded PLGA7505 MP at 4 h was over 80%, which was higher than that of MCZ powder. This enhancement of release rate is caused by the amorphization of ITCZ or MCZ in the PLGA matrix. MCZ-loaded PLGA7510 MP showed a sustained release profile up to 24 h, suggesting that MCZ exists in an amorphous form in the PLGA matrix;however, the release rate declined owing to the large molecular weight of PLGA. Therefore, the release enhancement of antifungal drugs loaded on PLGA MP could be achieved by their amorphization using a co-grinding method with ball milling.

关 键 词：Co-Grinding Method Ball Milling Poly (Lactide-co-Glycolide) ITRACONAZOLE MICONAZOLE Amorphization 

分 类 号：R31[医药卫生—基础医学]