[關(guān)鍵詞]
[摘要]
目的 制備不同高分子材料的槲皮素(QUR)結(jié)晶固體分散體(QUR-CSD),探討高分子材料對QUR-CSD體外溶出行為的影響及其可能的分子機(jī)制。方法 分別以泊洛沙姆188(P188)或聚乙二醇8000(PEG8000)為載體,QUR為模型藥物,采用旋轉(zhuǎn)蒸發(fā)法制備2種QUR-CSD(CSD-P188-QUR、CSD-PEG-QUR)。掃描電子顯微鏡(SEM)觀察樣品的微觀結(jié)構(gòu);粉末X-射線衍射法(PXRD)觀察晶體學(xué)特性;差示掃描量熱法(DSC)測定起始熔融溫度(Tc,onset);通過粉末溶出、本征溶出、片劑pH轉(zhuǎn)換溶出實(shí)驗(yàn)考察體外溶出行為。結(jié)果 CSD表征結(jié)果顯示,2種QUR-CSD中QUR均以結(jié)晶態(tài)存在,晶體粒徑、晶疇尺寸和結(jié)晶度均較原料藥有所減小,且以P188為載體的CSD對藥物上述性質(zhì)的影響更明顯。3種不同的體外溶出實(shí)驗(yàn)結(jié)果均顯示CSD-P188-QUR溶出行為最佳,其次是CSD-PEG-QUR,QUR最差。結(jié)論 2種高分子材料均可通過影響CSD中QUR的微觀結(jié)構(gòu)來改善其體外溶出行為,且以P188為載體的CSD對藥物微觀結(jié)構(gòu)的影響更為顯著。
[Key word]
[Abstract]
Objective To prepare quercetin (QUR) crystalline solid dispersions (QUR-CSD) with different polymer materials, and to investigate the effect of polymer materials on the dissolution behavior of QUR-CSD in vitro. Method Using poloxamer 188 (P188) or polyethylene glycol 8000 (PEG8000) as carriers, and QUR as a model drug, two kinds of QUR-CSD (CSD-P188-QUR and CSDPEG-QUR) were prepared by rotary evaporation method. Scanning electron microscope (SEM) was used to observe the microstructure of the sample. The crystallographic properties were observed by powder X-ray diffraction (PXRD). Onset temperature (Tc, onset) was determined by differential scanning calorimetry (DSC). The dissolution behavior in vitro was investigated by powder dissolution, intrinsic dissolution and tablet pH conversion dissolution tests. Results The CSD characterization results showed that QUR existed in the crystalline state in both preparations, and the crystal particle size, crystal domain size and crystallinity were all reduced comparison with API. The effect of CSD with P188 as carrier on the above properties was more significant. The three different dissolution experiments in vitro showed that CSD-P188-QUR had the best dissolution behavior, followed by CSD-PEG-QUR, and QUR was the worst. Conclusion Both polymer can improve the dissolution behavior by affecting the microstructure of QUR in CSD, and the CSD-P188-QUR has a more significant effect on the microstructure of the drug.
[中圖分類號]
R283.6
[基金項(xiàng)目]
國家自然科學(xué)基金資助項(xiàng)目(82060644);青海省科技廳項(xiàng)目資助(2022-ZJ-748)