联苯双酯过饱和自微乳释药系统的体内外评价

 目的 研究联苯双酯过饱和自微乳(BDD-S-SMEDDS的体外自乳化能力和体内药动学。方法 采用动态光散射法测定BDD-S-SMEDDS乳化后的粒径分布和Zeta电位;考察不同的促过饱和物质及不同用量对BDD-S-SMEDDS体外析晶的影响,并测定BDD-S-SMEDDS的体外溶出度;测定Beagle犬体内血药浓度,与市售滴丸相比,考察BDD-S-SMEDDS的体内药动学。结果 聚乙烯吡咯烷酮K30（PVP的促过饱和效果较好,其用量为0.5％～2％时均有较好的药物抑晶作用;BDD-S-SMEDDS加入水稀释后迅速乳化形成微乳,平均粒径为(38.40±0.28 nm,Zeta电位为(-8.00±0.99 mV;体外溶出度10 min时达到80％以上,比市售滴丸溶出显著提高;体内药动学数据表明,BDD-S-SMEDDS软胶囊达峰时间t_max提前,最大血药浓度ρ_max(143.29±52.91 μg·L-1是市售滴丸的2.6倍,AUC为市售滴丸的1.92倍。结论 BDD-S-SMEDDS体系中促过饱和物质PVPK30的加入,可以提高稳定性,减少表面活性剂的用量,并且显著提高BDD的体外溶出和体内吸收。     

Solid-State Emulsions: The Effects of Maltodextrin on Microcrystalline Aging

Pharmaceutical Research -     

Solid-State Emulsions: The Effects of Process and Storage Conditions

The effects of process and storage conditions of solid-state emulsions were studied. Oil-in-water emulsions may be prepared from solid state emulsions by adding an aqueous phase to the solid. Solid-state emulsions are prepared by processing an oil phase and an aqueous solution of matrix material via a solvent removal process. Sucrose, the carrier material utilized in this report, results in a metastable solid or glass, which can transform upon aging to a more stable thermodynamic state. Aging was determined by monitoring the crystallinity as a function of time, temperature, relative humidity, and grinding. The crystallinity of solid-state emulsions was determined with X-ray diffraction and differential scanning calorimetry. Results indicate that solid-state emulsions should be stored between 15 and 25% relative humidity at 25°C. Grinding has no apparent effect on the crystallinity of the sample, as detected by X-ray diffraction, although the microcrystallinity is increased. The utilization of silinized glassware enabled the sample-to-sample microcrystalline variability to be reduced.     

Solid-State Emulsions: Evaluation by 1H and 13C Solid-State Nuclear Magnetic Resonance

The molecular environment of sucrose and mineral oil within sucrose and mineral oil solid state emulsions was investigated by NMR techniques. The ¹³C and ¹H chemical shifts of sucrose and mineral oil to those observed in solid state emulsions (comprised of sucrose and mineral oil) were equivalent, indicating that the local structure of sucrose is unaffected by the presence of mineral oil in the solid-state emulsion. Cross-polarization, magic angle spinning ¹³C (CP-MAS) in conjuncton with single-pulse studies indicated that the ¹H-¹³C dipole-dipole interactions are very weak, i.e., mineral oil is highly mobile. Spinning side bands were observed, however, in ¹H single-pulse, magic angle spinning (SPMAS) spectra of the solid-state emulsion, indicating that the mineral oil has solid properties. Although the mineral oil was shown to be highly mobile, it also appears to be constrained or included by the sucrose.     

青蒿素类药物新制剂研究进展

青蒿素类药物除抗疟作用外,在治疗肿瘤、免疫和病毒等疾病方面具有潜在的临床应用价值。其传统制剂存在体内代谢迅速、消除半衰期短、生物利用度低、疟原虫复燃率高等缺点。研究显示,将该类药物制备成脂质体、固体分散体、环糊精包合物、自乳化和纳米粒等剂型可以改善其溶解度、提高生物利用度、减慢体内消除速度、增强缓释和靶向作用。因此,研制青蒿素类药物新剂型对提高其临床疗效和新适应证的开发具有重要意义。笔者通过文献检索,对国内外有关青蒿素类药物新剂型的研究进展进行了综述。     

双亲支链梳形共聚物的合成及其自乳化负载药物性能

通过可逆加成-断裂链转移（RAFT）聚合制备出聚甲基丙烯酸缩水甘油酯（PGMA）,经过叠氮钠与PGMA环氧基团的反应引入叠氮基和羟基,然后依次通过端炔基聚乙二醇（PEG-alk）与叠氮基的点击反应,己内酯（CL）在羟基存在下的开环聚合反应,获得双亲支链梳形共聚物（PGMA-g-PEG/PCL）。利用该梳形共聚物的两亲性,在氯仿-水混合体系中,进行自乳化高效负载阿霉素（DOX）,得到负载DOX的纳米粒子。利用核磁共振氢谱、红外光谱和凝胶渗透色谱确认了最终产物及其前体聚合物的结构。利用动态光散射、紫外可见分光光度计和扫描电镜研究该载药粒子在pH为7.0和5.0的水溶液中的释放。结果表明：该纳米粒子平均粒径约为100 nm,该粒子能有效释放DOX,在酸性条件下释放速率加快,且伴随PCL的降解。     

复方痛痹舒自微乳释药系统基质组成的研究

目的筛选复方痛痹舒自微乳释药系统(SMEDDS)的基质组成并确定配方比例。方法采用溶解度方法测定复方痛痹舒中主要有效成分在不同油相、乳化剂和助乳化剂中的溶解度,结合不同油相与乳化剂的配伍结果,筛选油相、乳化剂与助乳化剂,采用水滴定法绘制伪三元相图,以澄清度、粒径和自乳化时间为考察指标,筛定油相、乳化剂和助乳化剂的类型及其组成范围。结果复方痛痹舒SMEDDS基质组成:油相为肉豆蔻酸异丙酯(IPM),乳化剂为RH40/聚山梨酯-80(1∶1),助乳化剂为甘油;各相系占SMEDDS基质组成的比例范围按质量分数计:油相9.96%~40.49%,乳化剂23.31%~59.97%,助乳化剂19.83%~60.02%。结论筛定的复方痛痹舒SMEDDS基质,其分散相粒径可以达到10~100 nm,为进一步研究奠定基础。     

Self-Emulsifying Drug Delivery Systems: Formulation and Biopharmaceutic Evaluation of an Investigational Lipophilic Compound

Self-emulsifying drug delivery systems (SEDDSs) represent a possible alternative to traditional oral formulations of lipophilic compounds. In the present study, a lipophilic compound, WIN 54954, was formulated in a medium chain triglyceride oil/nonionic surfactant mixture which exhibited self-emulsification under conditions of gentle agitation in an aqueous medium. The efficiency of emulsifi-cation was studied using a laser diffraction sizer to determine particle size distributions of the resultant emulsions. An optimized formulation which consisted of 25% (w/w) surfactant, 40% (w/w) oil, and 35% (w/w) WIN 54954 emulsified rapidly with gentle agitation in 0.1 N HCl (37°C), producing dispersions with mean droplet diameters of less than 3 µm. The self-emulsifying preparation was compared to a polyethylene glycol 600 (PEG 600) solution formulation by administering each as prefilled soft gelatin capsules to fasted beagle dogs in a parallel crossover study. Pharmacokinetic parameters were determined and the absolute bioavailability of the drug was calculated by comparison to an i.v. injection. The SEDDS improved the reproducibility of the plasma profile in terms of the maximum plasma concentration (C _max) and the time to reach the maximum concentration (t _max). There was no significant difference in the absolute bioavailability of WIN 54954 from either the SEDDS or the PEG formulations.