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??OBJECTIVE To prepare mifepristone gastric retentive multi-unit pellet system (MUPs), and study its release behaviors in vitro. METHODS A sustained release layer and mucous adhesive layer were coated onto extrusion spherized mifepristone pellets. The gastric retentive sustained release pellets were mixed with granules which were wet granulated from micronized mifepristone and compressed into MUPs tablets. Investigation and evaluation of the in vitro release of mifepristone MUPs tablets were carried out from different aspects.RESULTS The turning point of pH value for the solubility of mifepristone was 3.0.Micronized mifepristone showed higher dissolving rate and apparent solubility.The gastric retentive mifepristone MUPs tablets had faster release than marketed mifepristone tablets. The in vitro adhesive experiment with pig stomach showed that mucous adhesive mifepristone pellets could be entrapped into the gastric mucous and retained for a long time. The accelerated stability study showed that mifepristone MUPs tablets were as stable as marketed mifepristone tablets.CONCLUSION Novel mifepristone gastric retentive MUPs tablets are successfully prepared.The release characteristics in vitro indicate that the product may have higher bioavailability than marketed mifepristone tablets with significantly lower variability.     

基于渗透压原理实现尼莫地平可控释药系统的研究

目的 制备基于渗透压原理的尼莫地平渗透泵胶囊,考察影响其释药行为的因素,优化处方并考察其释放机制。方法 根据尼莫地平渗透泵胶囊在体外累积释放度与零级方程拟合度,对囊壳、含药层、助推层的辅料种类和用量进行单因素考察,选出释放主要影响因素为致孔剂用量、含药层并检测其渗透压活性物质用量和膨胀剂用量,利用Box-Behnken设计法对其进一步优化,确定最优处方。制备3批尼莫地平渗透泵胶囊体外释放度与零级方程拟合考察其释药特性,再使用相似因子法(f₂)进行释放机制研究。结果 尼莫地平渗透泵胶囊最优处方为致孔剂(PEG 6000)用量14 mg、含药层渗透压活性物质(NaCl)用量33.7 mg、膨胀剂(PEO 800万)用量33.2 mg,制备的尼莫地平渗透泵胶囊在12 h内药物释放较完全,致孔剂为药物提供释药途径,渗透压活性物质为释药动力。结论 尼莫地平渗透泵胶囊控释效果良好,累积释放度大于90%,并且接近零级释放方程,符合预期。     

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??OBJECTIVE To improve the dissolution rate of fenofibrate (FNB) by using starch source mesoporous carbon (SMC) as a carrier and achieve controlled release of the drug by utilizing double-layer osmotic pump technology to improve the oral bioavailability. METHODS FNB was loaded into the mesoporous of NMS by adsorption method to prepare the drug loading system (FNB-SMC). Differential scanning calorimetry (DSC) and powder X-ray diffraction (PXDR) were used to characterize the present state of the drug before and after being loaded. The dissolution rate of FNB-SMC was investigated by in vitro dissolution test, and the formulation of the double-layer osmotic pump tablets of FNB-SMC was optimized. The oral bioavailability of the self-made tablet was investigated by in vivo experiment in rabbits. RESULTS FNB existed in the mesoporous of SMC in an amorphous state. The in vitro dissolution test showed that NMS could significantly increase the dissolution rate of FNB, and the double-layer osmotic pump technology could achieve Zero-order release of the drug. The in vivo experiments showed that the oral bioavailability of the self-made tablets was significantly improved. CONCLUSION The combination of starch source mesoporous carbon carrier and double-layer osmotic pump technology prevente the burst effect and significantly improve the oral absorption of FNB.     

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??OBJECTIVE To prepare nano-micelles with amphiphilic self-assembly poly (ethylene glycol)-co-poly (propylene sulfide) (PEG-PPS) copolymer as carrier to study the release characteristics of tilianin and investigate its activity to against H9c2 cell apoptosis in vitro. METHODS An amphiphilic diblock PEG-PPS polymer was used as a carrier material to prepare the tilianin-containing nano-micelles by solvent evaporation. The morphology, particle size and distribution, drug loading and encapsulation rate and in vitro drug release behavior were characterized, H9c2 rat myocardial cell injury model was established by hypoxia/reoxygenation process. Using propranolol (Pro) as a positive control, the morphology of injured cardiomyocytes was observed by microscope. Cell proliferation and cell apoptosis was detected to evaluate the protective effect of blank micelles, tilianin and tilianin loaded nano-micelles on H9c2 cells induced by hypoxia/reoxygenation. RESULTS Tilianin-loaded nano-micelles was spherical with uniform particle size distribution. The drug loading was 3.82%. The average particle diameter of tilianin-loaded nano-micelles was 137 nm, polydispersity coefficient was 0.162 and the encapsulation efficiency was 91.45%. In vitro drug release studies showed that there was no drug-induced burst release of tilianin-containing nano-micelles and sustained release characteristics, and the presence of hydrogen peroxide significantly promoted the release of tilianin from the nano-micelles. In vitro cytotoxicity experiments showed that when the concentration of tilianin 5 ??g??mL^-1, the cell viability of tilianin-loaded nano-micelles was significantly higher than the corresponding concentration of tilianin and PEG-PPS polymer nano-micelles. In vitro anti-apoptotic activity experiments show that tilianin-loaded nano-micelles on H9c2 cell apoptosis induced by hypoxia-reoxygenation have a significant inhibitory effect and was provided inhibition of apoptosis with propranolol. CONCLUSION Tilianin-loaded nano-micelles have uniform particle size and distribution, sustained release and oxidation characteristics, has a significant protective and apoptosis-inhibiting effect on H9c2 cell injury induced by hypoxia-reoxygenation, which can be used as a promising drug delivery system for the treatment of myocardial ischemia-reperfusion injury.     

PLGA-PEG-PLGA温敏水凝胶包载多柔比星脂质体用于治疗小鼠骨肉瘤的研究

目的 制备聚乳酸乙醇酸-聚乙二醇-聚乳酸乙醇酸共聚物(PLGA-PEG-PLGA)水凝胶包载的多柔比星(Doxorubicin,DOX)脂质体的复合载体,并考察其体外性质和抑瘤效果。方法 采用水化薄膜法制备DOX脂质体,考察其粒径分布和包封率,再利用PLGA-PEG-PLGA水凝胶包载制备得到的DOX脂质体得到DOX-Lip-Gel复合载体,考察其体外释放、黏性测试以及对荷瘤小鼠的治疗效果。结果 制备得到的DOX-Lip的粒径约为(89.3±4.7) nm,包封率约为(85.3±2.6)%,PLGA-PEG-PLGA水凝胶在25 ℃处于溶液状态,而在37 ℃时可凝固成胶,黏性测试结果表明水凝胶的相变温度约为30 ℃。并且水凝胶聚合物具有良好的生物相容性,在体内可以缓慢的降解。与对照组相比,DOX-Lip-Gel可以缓慢的释放药物,且释放期长达200 h。体内抑瘤实验表明DOX-Lip-Gel具有更好的抗肿瘤效果。结论 制备得到的DOX-Lip-Gel对荷瘤小鼠进行瘤周给药,对抑制骨肉瘤在小鼠体内的增长具有显著的抑制作用。     

小檗碱磷脂固体分散体改善氧化应激治疗2型糖尿病

目的 制备包载小檗碱(BBR)的磷脂固体分散体促进药物吸收,增强降糖、降脂药效,并初步阐明其抗2型糖尿病(T2DM)作用机制.方法 溶剂挥发法制备小檗碱磷脂固体分散体(SD),对其粒径、形貌、体外释放、胃肠道吸收、治疗T2DM药效和作用机制进行了充分研究.结果 SD在水溶液中粒径约为118 nm,形貌为球形;相比于游离...     

国产非那雄胺片与原研制剂体外溶出一致性评价及采用计算机模拟技术建立体内外相关性模型研究

目的 通过比较国产非那雄胺片与原研制剂的体外溶出行为,评价仿制药与参比制剂的质量一致性,利用计算机模拟技术分析体内外相关性。方法 参照《中国药典》2015年版方法(2020年版《中国药典》该项目没有变化),分别考察国产制剂与原研制剂在4种不同溶出介质(pH 1.2盐酸溶液、pH 4.5醋酸盐溶液、pH 6.8磷酸盐溶液、水)中的体外溶出行为。同时借助GastroPlus^TM软件结合体外溶出试验结果,建立非那雄胺片体内外相关性模型。结果 在选定条件下,国内15家制药公司中有3家公司产品在4种溶出介质中的溶出曲线均与原研制剂相似。软件分析结果提示,体外溶出曲线与软件模拟的体内行为不相似。结论 大部分非那雄胺片仿制制剂在体外的溶出曲线与原研制剂存在一定的差异,国产非那雄胺片工艺水平及处方有待提高,反映体内释放行为的生物体相关溶出条件有待进一步研究。     

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??OBJECTIVE To evaluate the properties of co-processed excipient of mannitol and polyplasdone (Man-Cro) and apply it in direct compression of orally disintegrating tablets. METHODS The physical and micromeritic properties of the co-processed excipient were compared with those of mannitol, polyplasdone, and physical mixture of the two compounds. The interaction between the two components was studied by using FT-IR, SEM, DSC and X-RD. The flowability and compressibility of the Man-Cro co-processed excipient were also compared with the two components by determining the angle of repose, bulk density, tap-density, Carl index and Kawakita??s equation. The co-processed excipient was applied to prepare ibuprofen orally disintegrating tablets. The in vitro dissolution and bioavailability of the tablets were evaluated. RESULTS The co-processed excipient of mannitol and polyplasdone formed novel aspheric particles after cocrystallization. The excipient showed good flowability, compressibility, filling ability and disintegrability. Compared with commercially available ibuprofen tablets, the ibuprofen orally disintegrating tablets prepared with the co-processed excipient had more rapid in vitro dissolution. And the homemade and commercially available preparations were bioequivalent in rats. CONCLUSION The co-processed excipient is superior to physical mixture as drug carrier and suitable for preparation of orally disintegrating tablets by direct compression.     

米诺地尔-生物可溶性微针的制备及评价

目的 制备治疗脱发的米诺地尔-甲基丙烯酸酰化明胶(GelMA)生物可溶性微针,并对其进行表征和评价。方法 以生物可溶性水凝胶GelMA为基质,采用模印法和紫外交联法制备米诺地尔-GelMA生物可溶性微针,分别采用光学和荧光显微镜表征其形貌,采用机械性能和溶胀率测定考察交联度对微针机械强度和吸水性的影响,采用体外药物释放实验考察其体外药物释放速度;采用动物透皮实验评价其透皮效果。结果 所得微针机械强度足以穿透皮肤实现透皮给药。微针吸水性良好,使其在刺入皮肤后通过吸附溶胀和降解释放包合的米诺地尔。结论 以GelMA为基质的米诺地尔-GelMA生物可溶性微针具有生物相容性高、可缓释、靶向给药等优点。微针贴片便于携带,使用方便,与其他剂型相比有独特优势,具有较好的应用前景。     

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??OBJECTIVE To prepare lappaconitine(LA)-loaded chitosan/ sodium ??-glycerophosphate(CS/??-GP) thermosensitive hydrogels and investigate its phase transition mechanism of gel formation process and release properties in vitro. METHODS The injectable CS/??-GP thermosensitive hydrogels were prepared with biodegradable CS as carrier material and ??-GP as coagulation accelerator. The release behavior in vitro was studied by dynamic dialysis, and the phase transition mechanism of gel formation process was further investigated by rheological method. RESULTS The optimized process condition was as follows:the concentration of ??-GP and CS was 560 and 22 mg??mL^-1, respectively, CS was dissolved by 0.1 mol??L^-1 HOAc, and the valume ratio of CS to ??-GP was 8.75??1.25(V/V), the gelation time of CS/??-GP thermosensitive hydrogels with volume ratio of 8.75??1.25(V/V) at 37 ?? was 5 min 38 s. The in vitro release study showed that these injectable CS/??-GP thermosensitive hydrogels had sustained release effect for LA, and the release behavior could be well described by the Higuchi model and Korsmeyer-Peppas model. The mechanism of LA releasing from CS/??-GP thermosensitive hydrogels was attributed to drug dissolution and diffusion. Rheological studies showed that the CS/??-GP thermosensitive hydrogels belonged to thixotropic system and exhibited non-Newtonian and shear-thinning fluid behavior as well as ??solid-like?? gelatin behavior. CONCLUSION LA-Loaded CS/??-GP injectable thermosensitive hydrogels with good elasticity and gel strength properties are prepared successfully, and they show sustained release effect of LA in vitro.