苯丁酸氮芥脂质体的制备及处方因素考察

目的 制备苯丁酸氮芥脂质体并优化其处方。方法 薄膜超声分散法制备苯丁酸氮芥脂质体,采用微柱离心-HPLC法测定其包封率,以包封率为考察指标,研究膜材比、药脂比、水相介质pH值以及磷脂浓度等因素对脂质体包封率的影响;通过正交试验对处方进行优化,并进行质量评价。结果 苯丁酸氮芥脂质体优化后的制备处方为胆固醇与磷脂质量比1∶3、药脂比1∶10、水相介质pH值为7.4、磷脂浓度为0.3%。按该处方制得的苯丁酸氮芥脂质体包封率>87%,平均粒径为84.71 nm,PDI为0.167。结论 优选处方稳定可行,制备的苯丁酸氮芥脂质体包封率高、粒径小且均匀。     

西罗莫司脂质体的体外释放研究

目的:研究西罗莫司脂质体的体外释放特性。方法:建立反相高效液相色谱法测定西罗莫司含量;采用反透析法,以500mL 20%乙醇为释放介质,考察24 h不同时间西罗莫司脂质体的体外累积释放率,利用药物释放模型方程拟合释放曲线。结果:西罗莫司检测浓度的线性范围为0.5～20 μg.mL~(-1)(r=0.999 8),平均回收率为99.42%,RSD=1.23%;脂质体前4 h的释药速率快,累积释放率为50%,之后释药相对缓慢,24 h的累积释放率为80%,释放曲线符合一级动力学方程。结论:西罗莫司脂质体具有一定缓释效应,其体外释放属于浓度依赖型渗透释药。     

高纯度西罗莫司的制备

研究西罗莫司工艺,改进化学提取纯化步骤,使西罗莫司纯度高达99.8%,HPLC图谱中相对保留时间(RRT)为1.19的微量杂质稳定控制在0.05%以下,达到特殊用途的质量要求.     

西罗莫司滴眼液的质量控制及稳定性考察

目的建立西罗莫司滴眼液的质量控制方法并观察其稳定性。方法根据中国药典2010年版眼用制剂项下有关规定拟定西罗莫司滴眼液的质量控制方法,用高效液相色谱法测定西罗莫司的含量,观察家兔眼部刺激性,并对制剂的稳定性进行考察。结果在20～80μg/ml浓度范围内,西罗莫司峰面积和质量浓度呈良好的线性关系(r=0.9997),平均回收率为100.09%,RSD为0.22%,精密度高,耐用性好,样品溶液可以在室温环境下24h内稳定。滴兔眼后无刺激性,而且稳定性相对较好。结论本方法专属性强,操作简便,结果准确,可用于西罗莫司滴眼液的质量控制。     

西罗莫司缓释片的制备及其释药因素考察

目的制备西罗莫司缓释片并对其释药因素进行考察。方法采用羟丙基甲基纤维素（HPMC）为基本骨架材料制备了西罗莫司凝胶骨架片,对影响释药的因素,如采用羟丙基甲基纤维素（HPMC）规格、用量、填充剂种类、致孔剂用量、压片压力及释放介质等进行了考察。结果以30%羟丙基甲基纤维素（HPMC K4M）为骨架材料、2%乳糖为致孔剂、微晶纤维素（MCC）为填充剂时,缓释片呈明显一级释放特征。结论该制剂在体外具有良好的缓释效果,且制备工艺简单易行。     

阿奇霉素囊泡的制备及处方考察

目的 制备阿奇霉素(AZI)囊泡并对处方进行筛选,得到较高包封率的囊泡制剂.方法 采用薄膜蒸发-冻融法制备AZI泡囊,反透析法测定包封率,以包封率和载药量为评价指标,单因素考察冻融次数、胆固醇与吐温质量比、十八胺百分含量以及投药量因素对囊泡的影响.结果 实验结果表明冻融3次、胆固醇与吐温质量比为1:3、十八胺百分含量为3％和投药量10.0mg时为最佳处方,制得的囊泡包封率由最初的(64.00±1.91)％提高为(92.87±0.77)％,粒径为(5.87±1.18)μm,zeta电位为±(12.5±0.02)mY,室温下稳定.结论 最佳处方制得的AZI囊泡的包封率高,重现性好.     

高乌甲素脂质体凝胶制备工艺筛选实验研究

目的：研究乙醇注入法制备高乌甲素脂质体凝胶的工艺。方法：采用单因素实验分析药脂比、磷脂胆固醇比、水化液pH、水化温度筛选影响包封率及载药量的因素,再采用正交试验优选最佳处方;制备得到高乌甲素脂质体后,单因素实验筛选最佳卡波姆用量及pH,得到最适宜脂质体凝胶配方。结果：采用正交试验法确定高乌甲素脂质体最佳处方工艺组合为卵磷脂：胆固醇为6∶1、药脂比为1∶10、水化温度为55 ℃,水化液pH值为7.0,该处方制备的脂质体包封率高,粒径分布均匀;当卡波姆-940用量为1%、在pH 6~7时,所制备的高乌甲素脂质体凝胶易涂布、黏度适宜。结论：制备的高乌甲素脂质体凝胶工艺简单可行,包封率较高,可以进一步研究。     

六甲蜜胺脂质体的制备及影响因素考察

目的:制备六甲蜜胺脂质体并对处方进行筛选,以期得到符合包封率(encapsulation efficiency,EE%)要求和稳定均一的脂质体制剂.方法:选用乙醇注入法制备六甲蜜胺脂质体,以包封率为评价指标,进行单因素考察以及正交试验.结果:通过单因素考察选择出对脂质体包封率影响较大的因素,如磷脂种类、磷脂浓度、水相介质pH值以及脂胆比等,并以此进行正交试验.结论:确定了最优处方,制备成稳定均一的六甲蜜胺脂质体.     

单因素和正交设计法优化苦参素空间稳定脂质体处方

目的:优化苦参素空间稳定脂质体的处方。方法:以高纯蛋黄卵磷脂PC-98T、胆固醇和PEG2000-DSPE为载体,采用乙醇注入法制备苦参素空间稳定脂质体。以包封率为评价指标,采用单因素考察法和正交设计法对其处方进行优化。结果:最优处方是磷脂与胆固醇的质量比(5:1),磷脂与药物质量比为(4:1),磷脂与PEG2000-DSPE质量比为(12:1),包封率大于80%。结论:该法制得的脂质体包封率符合中国药典要求(≥80%),平均粒径较小,说明该处方优化成功,制备工艺简单、可行,适宜工业化生产。     

布洛芬乙醇脂质体的制备及体外透皮特性研究

目的:制备布洛芬乙醇脂质体并考察其透皮特性。方法:采用注入法制备布洛芬乙醇脂质体;以包封率为指标,考察磷脂浓度、乙醇浓度、药脂比等因素对脂质体包封率的影响;用Franz扩散池进行离体皮肤渗透实验,测定布洛芬在接收液内的累积渗透量及皮内滞留量。结果:磷脂、乙醇、布洛芬分别占处方量的3%,45%和1%时制得的乙醇脂质体包封率为(72.93±1.12)%;乙醇脂质体的累积渗透量分别为乙醇溶液及脂质体的1.91倍和3.46倍;24 h后皮肤中药物滞留量依次为:乙醇脂质体>45%乙醇水溶液>脂质体。结论:乙醇脂质体可显著增加布洛芬的皮肤渗透性及皮内滞留量。     

棓丙酯脂质体的制备与表征

目的制备棓丙酯脂质体,并对其进行理化性质的表征和释放度的评价。方法采用薄膜分散法制备棓丙酯脂质体,超滤离心法测定脂质体的包封率,正交设计优化处方,并对其包封率、粒径、Zeta电位、形态及体外释放行为进行综合评价。结果正交设计优化最终处方为磷脂浓度5 mg.mL-1、药脂比1∶5、磷脂胆固醇比5∶1、水化介质离子强度20 mmol.mL-1,所得脂质体包封率为89.6%、粒径为181.3 nm、Zeta电位为-21.8 mV、4 h体外释放达到80%。结论制备的棓丙酯脂质体包封率高,粒径小而均一,体外释放完全。     

正交试验优选二氢青蒿素脂质体的制备工艺

目的:优选二氢青蒿素脂质体的制备工艺。方法:以大豆磷脂与胆固醇的质量比、脂质与药物的质量比、水合溶液的种类为考察因素,以包封率为评价指标,利用正交试验优选制备工艺。结果:优选的工艺为采用薄膜-超声法,大豆磷脂与胆固醇的质量比为5∶1,脂质与药物的质量比为5∶1,以0.9%NaCl注射液为水合溶液。制得的脂质体形态均匀,包封率>85%。结论:该制备工艺和处方可以得到高包封率和稳定的二氢青蒿素脂质体。     

Use of liposomes as carriers for immunomodulatory polypeptides: Studies on thymostimulin encapsulation and retention

The incorporation of thymostimulin, an immunoactive hormone extracted from calf thymus, into liposomes was characterized by means of DSC analysis. Changes in vesicle composition, as well as in the presence of cholesterol, led to variations in thermotropic behaviour and influenced their incorporation efficiency and stability. Among the prepared formulations, liposomes prepared using equimolar amounts of DPPC and DMPC showed the highest value (80%) for drug incorporation.     

Long circulating liposomes of 2',3'-dideoxyinosine: Formulation and stability

2',3'-Dideoxyinosine (ddI), an anti-human immunodeficiency virus (HIV) agent, was encapsulated in liposomes. The influence of the phospholipid/cholesterol ratio, concentration of phospholipid (PL), and chain length of PL on the encapsulation of ddI in multilamellar vesicles (MLVs), frozen and thawed multilamellar vesicles (FAT MLVs), and large unilamellar vesicles (LUVs) was studied. An optimum formulation was then selected to prepare long circulating liposomes. Stability studies at 4, 25, and 37°C and under certain stress conditions were performed. Release characteristics in phosphate buffer (pH 7.4) at 37°C were studied. Results show an increase in encapsulation efficiency (EE) with increasing amounts of cholesterol, a decrease in EE and increase in encapsulation yield (EY) with increasing concentrations of PL, and an increase in EE with increases in PL chain length, in both MLVs and LUVs. Freezing and thawing of MLVs had no influence on EE at a PL concentration of 10 mg/mL but increased EE at higher concentrations of PL. Various stability tests showed the formulation to be stable to leakage of entrapped drug when stored at 4, 25, and 37°C for 6 months, when subjected to mechanical stress, and on exposure to human serum. The release studies indicated that 70% of ddI was released over a period of 72 h.     

伊曲康唑脂质体的制备工艺研究

目的:优化伊曲康唑脂质体的制备处方和工艺.方法:采用正交设计法,以伊曲康唑脂质体冻干粉重建包封率、粒径分布、渗漏率3个指标综合评分.结果:伊曲康唑脂质体的最佳工艺处方为药物-脂材比1∶30,胆固醇-磷脂比1∶5.5,去氧胆酸钠-脂材比1∶7,甘露醇和乳糖的用量为处方总重的60%,水合介质为磷酸盐缓冲液(pH=6.0),采用薄膜水化超声-冷冻干燥工艺制备.结论:按最优处方制得的脂质体的外观比较圆整,包封率和粒径均较好.     

卡莫氟固体脂质纳米粒的制备及工艺研究

目的:制备卡莫氟固体脂质纳米粒并考察其药剂性质。方法:采用高压均质法制备卡莫氟固体脂质纳米粒混悬液,以单因素考察和正交设计法筛选处方和工艺,并考察其形态、粒径、载药量及包封率。结果:优选出的较佳处方大豆卵磷脂、泊洛沙姆188、吐温-80和硬脂酸用量分别为8.0、12.0、1.0、7.5mg·mL-1;所制得的固体脂质纳米粒为圆整的实体粒子,表面光滑,平均粒径为78.7nm,载药量为23.47%,包封率为82.33%。结论:高压均质法可用于卡莫氟类脂溶性药物固体脂质纳米粒的制备。     

A quality by design (QbD) case study on liposomes containing hydrophilic API: II. Screening of critical variables, and establishment of design space at laboratory scale

Two statistical designs were used in this case study as part of an investigation into the feasibility and the advantages of applying QbD concepts to liposome-based complex parenteral controlled release systems containing a hydrophilic active pharmaceutical ingredient (API). The anti-viral drug Tenofovir was used as a model compound. First design (Plackett-Burman) was used to screen eight high-risk variables obtained from risk analysis and assess their impact on liposome characteristics (drug encapsulation efficiency, particle size, and physical stability). It was discovered that out of eight high-risk variables only lipid and drug concentration had significant effects on the drug encapsulation efficiency. This allowed the use of a central composite design (CCD) (with more predictive capability) to fully elucidate the relationship between lipid concentration, drug concentration and encapsulation efficiency. On comparing the CCD model generated response surface with additional data points, the accuracy and robustness of the model was confirmed. Using this developed model, the design space for Tenofovir liposomes preparation has been established in a laboratory setting, within which the preparation variability is minimized. With regard to sample storage stability, it was shown that at 4 °C the prepared Tenofovir liposomes, dispersed in aqueous phase, achieved stability for at least 2 years. These principles can be applied to liposomes containing other hydrophilic APIs, and can provide time and cost saving to industrial formulation scientists, and result in a more robust liposome preparation process.     

奥沙利铂纳米结构脂质载体的处方研究

目的研究奥沙利铂纳米结构脂质载体最佳处方。方法采用正交设计法,以包封率为指标,对奥沙利铂纳米结构脂质载体的最佳处方进行实验研究。结果优化的最佳处方为单硬脂酸甘油酯(GMS)与中链甘油三酸酯(MCT)的质量比为3∶2;大豆磷脂(PC)用量为2.0%;ELP用量为2.0%。结论此优化处方具有较好的粒度和包封率。     

灯盏花素脂质体的制备工艺

目的研究灯盏花素脂质体的制备工艺。方法采用薄膜蒸发-探头超声法和冷冻干燥法制备灯盏花素脂质体,在单因素考察基础上采用正交试验设计。以包封率为评价指标,筛选脂质体制备的最佳工艺条件。冻干品水合后,在电镜下观察灯盏花素脂质体的形态,利用马尔文测定仪测定脂质体的粒径,用RP-HPLC法测定其包封率。结果灯盏花素脂质体的最佳工艺处方为药脂比1∶5,SPC∶CH为2∶1,二氯甲烷用量为10 ml。冻干保护剂蔗糖用量为10%。制备3批脂质体,包封率平均为87.5%,平均粒径为378.3 nm。结论所制脂质体包封率较高,粒径分布较均匀。