螺旋藻多糖的提取工艺研究

目的：研究螺旋藻多糖最佳的提取工艺。方法：采用均匀设计和球面对称设计方法考察螺旋藻多糖提取过程中，提取温度、提取时间、提取溶液的pH值3个因素对多糖分离的影响。结果：通过球面对称设计回归方程得出的优化条件是：提取温度77.3℃，时间6.99 h，溶液pH值10.85，多糖提取率为5.13%；通过均匀设计得出的优化条件是提取温度96.42℃，提取时间7.77 h，溶液pH值8.24，多糖提取率为4.21%。结论：球面对称设计提取螺旋藻多糖的优化条件的可信度高于均匀设计。     

球面对称设计筛选盐酸普萘洛尔药物树脂渗透泵控释片

目的：对盐酸普萘洛尔药物树脂渗透泵控释片制备工艺进行研究。方法：采用球面对称设计法对处方进行筛选。结果：最优处方组成为：片心中氯化钠30 mg,包衣液中醋酸纤维素与聚乙二醇的比例为5：1,包衣膜增重8％。最优处方在2～14 h内呈现零级释放特征,24 h累积释放量为94％。结论：经球面对称设计法优化的处方体外释放理论值与试验值吻合良好且符合设计要求。     

酵母发酵生产谷胱甘肽的培养基优化

目的应用Plackett-Burman设计和球面对称设计实验,对酵母发酵生产谷胱甘肽的培养基进行优化。方法首先通过Plackett-Burman设计方法从10个因素中选择出对发酵产量影响较大的因素,即葡萄糖、酵母膏和半胱氨酸含量,然后用球面对称设计对这3个因素各取5个水平进行优化。结果最佳培养基组成为:葡萄糖23.64g/L,酵母膏29.07g/L,半胱氨酸1g/L,(NH4)2SO42g/L,蛋白胨5g/L,KH2PO41g/L,MgSO41g/L,NaCl2g/L。在优化条件下,发酵液中谷胱甘肽积累量可达162.3mg/L,比优化前产量提高约56.2%。结论证明用Plackett-Burman设计和球面对称设计寻求菌体积累谷胱甘肽的最佳培养基组分是可行的。     

球面对称设计筛选罗沙替丁缓释片的处方及其释放度考察

目的研究球面对称设计法在缓释片处方优化中的应用并考察其释放度。方法采用球面对称设计法,以海藻酸钠、羟丙基甲基纤维素、十八醇用量3因素为考察对象,对罗沙替丁缓释片的处方进行优化并制备缓释片;另测定释放度,并对数据进行评分及统计学分析。结果采用球面对称设计法,可得到影响因素的二项式方程和优化处方,且试验值与预测值非常接近。结论采用球面对称设计法对罗沙替丁缓释片的处方进行优化和预测可行。     

球面对称设计和常规正交试验方法用于清中饮制剂制备工艺研究的比较

比较了用球面对称设计方法和常规正交试验方法用于清宫饮制剂中紫河车酶水解和当归等生药水提取最佳工艺选择，实验结果表明于面对称设计优化结果与实验值更为接近，精密度明显高于正交试验。     

尼美舒利缓释胶囊的研究

目的研究尼美舒利缓释胶囊的制备方法,筛选最佳制备工艺条件。方法采用淀粉和糊精为赋形剂制备尼美舒利含药微丸,乙基纤维素为包衣材料,采用悬浮包衣法制备了尼美舒利缓释微丸,用正交实验表的安排进行试验,并确定其最佳工艺条件,按优化后的结果选择实验条件进行重复实验,测定体外释放度以考察缓释效果。结果制备的缓释胶囊在12h内释药符合Higuchi模型动力学过程。结论按优化结果选择的制备工艺条件所制备的尼美舒利缓释胶囊其缓释效果好,达到设计要求。     

球面对称设计优化胸腺五肽三甲基壳聚糖纳米粒的制备条件

目的探讨以三甲基壳聚糖为材料制备胸腺五肽纳米粒的制备条件。方法离子胶凝法制备胸腺五肽三甲基壳聚糖纳米粒(Tp5-TMC-NP),用球面对称设计优化制备条件,以粒径和包封率为评价指标,考查TMC浓度(X1)、海藻酸钠浓度(X2)、Tp5加入量(X3)三个指标对制备条件的影响,将实验结果用数学方法处理并进行方程模型拟合,根据拟合方程及由此绘制的反应曲面图(Response Surface Plot)考察指标的最优值和各因素相对应的最佳取值范围。结果以优化条件制得纳米粒粒径110.6 nm,药物包封率78.8%。结论制备方法简便,具有工业化生产的可行性。     

替莫唑胺聚氰基丙烯酸正丁酯纳米粒的制备

目的:优化工艺制备替莫唑胺聚氰基丙烯酸正丁酯纳米粒(TMZ-PBCA-NP)。方法:以α-氰基丙烯酸正丁酯(BCA)为载体,采用乳化聚合法制备TMZ-PBCA-NP,并以PluronicF-68作为表面活性剂,通过考察粒径大小和包封率2个指标,在单因素实验初选的基础上,正交设计法优化处方和制备工艺。结果:制备TMZ-PBCA-NP的优化条件为反应体系pH2.5,用1%PluronicF-68作为表面活性剂,TMZ用量5 mg,BCA单体用量0.1 mL,按优化条件所制备的TMZ-PBCA-NP平均粒径(135.8±11.3)nm,多分散系数为0.19,表面电位(-24.8±2.2)mV,包封率(44.23±2.04)%,载药量(2.80±0.05)%。结论:通过优化处方和制备工艺,采用乳化聚合法可制备出TMZ-PBCA-NP,对拓展TMZ临床给药新剂型提供一定的参考。     

利福平聚乳酸-羟基乙酸共聚物纳米粒的成型工艺及制剂学性质分析

目的优化利福平聚乳酸-羟基乙酸共聚物纳米粒(RFP-PLGA-NPs)的制备工艺,并分析其制剂学性质。方法以PLGA为载体,采用改良的自乳化溶剂蒸发法(M-SESD)制备RFP-PLGA-NPs。以粒径、包封率、载药量为指标,采用正交设计法优化处方和制备工艺。结果制备RFP-PLGA-NPs的优化条件为PLGA 100 mg,poloxsmer 188质量分数1.0%,丙酮与乙醇体积比3:1,有机相体积15 mL。按优化条件所制备的RFP-PLGA-NPs的粒径为(128.73±4.07)nm,多分散系数(PDI)为0.046～0.105,包封率(65.84±0.69)%,载药量(3.78±0.14)%。结论该工艺简单、稳定性好,为后续RFP-PLGA-NPs的体内研究奠定了基础。     

丹参酮微乳制备工艺的初选及优化

目的寻找丹参酮微乳最佳的处方和制备工艺。方法选择大豆磷酯与F-68为乳化剂,甘油和山梨醇为辅助乳化剂。通过单因素实验初选,均匀设计优化处方和制备工艺。结果优化条件下,制备的丹参酮微乳为淡红色透明胶体溶液,平均粒径为42.1 nm,包封率为98.47%,载药量为0.468%。结论该优化条件可作为丹参酮微乳最佳的处方和制备工艺。     

Optimizing the novel formulation of liposome-polycation-dna complexes (lpd) by central composite design

LPD vectors are non-viral vehicles for gene delivery comprised of polycation-condensed plasmid DNA and liposomes. Here, we described a novel anionic LPD formulation containing protamine-DNA complexes and pH sensitive liposomes composed of DOPE and cholesteryl hemisuccinate (Chems). Central composite design (CCD) was employed to optimize stable LPD formulation with small particle size. A three factor, five-level CCD design was used for the optimization procedure, with the weight ratio of protamine/DNA (X1), the weight ratio of Chems/ DNA (X2) and the molar ratio of Chems/DOPE in the anionic liposomes (X3) as the independent variables. LPD size (Y1) and LPD protection efficiency against nuclease (Y2) were response variables. Zeta potential determination was utilized to define the experimental design region. Based on experimental design, responses for the 15 formulations were obtained. Mathematical equations and response surface plots were used to relate the dependent and independent variables. The mathematical model predicted optimized X1-X3 levels that achieve the desired particle size and the protection efficiency against nuclease. According to these levels, an optimized LPD formulation was prepared, resulting in a particle size of 185.3 nm and protection efficiency of 80.22%.     

重组人血管内皮抑制素壳聚糖纳米粒的制备

目的:通过星点设计-效应面法优化重组人血管内皮抑制素(Endostar)壳聚糖纳米粒的制备工艺。方法:以壳聚糖浓度、三聚磷酸钠(TPP)浓度及壳聚糖溶液与TPP溶液体积比为考察因素,以载药量、包封率和粒径为指标,采用多元线性回归和多元非线性回归拟合选择合适模型,并根据最佳模型绘制效应面图,选择最佳处方,并进行预测分析,同时考察最佳处方的体外释放。结果:用多元非线性回归对实验中各因素和指标进行拟合明显优于线性拟合。最佳处方制备的Endostar载药壳聚糖纳米粒,载药量、包封率及粒径的实测值与预测值的偏差均在±7%以内,体外释放1周累积释放80%。结论:通过星点设计-效应面法可以准确快速优化处方工艺。优化后的工艺制备的纳米粒可以延缓Endostar的释放,达到了缓释效果,符合预期的试验目标。     

Quality by design: screening of critical variables and formulation optimization of Eudragit E nanoparticles containing dutasteride

The study was aimed at screening, understanding, and optimizing product variability of dutasteride-loaded Eudragit E nanoparticles prepared by solvent displacement using Plackett–Burman screening and a central composite design. The independent process and formulation factors selected included: drug loading (%), solute concentration (mg/mL), Soluplus concentration (mg/mL), injection rate (mL/min), organic solvent type (methanol or ethanol), stirring rate (rpm), and organic-to-aqueous phase volume ratio. Among these factors, solute concentration was associated with increased particle size, broad particle size distribution, and enhanced entrapment efficiency. On the other hand, Soluplus concentration played a role in decreasing particle size, narrowing particle size distribution, and reducing entrapment efficiency. Other formulation and process factors did not have a significant impact on nanoparticle properties, assuming they were within the limits used in this study. The optimized formulation was achieved with 20 mg/mL solute and 3.22 mg/mL Soluplus, and the observed responses were very close to the values predicted using the response surface methodology. The results clearly showed that quality by design concept could be effectively applied to optimize dutasteride-loaded Eudragit E nanoparticles.     

姜黄素醇质体的制备及其质量评价

目的:制备姜黄素醇质体,并考察其理化性质.方法:采用乙醇注入法制备姜黄素醇质体,以包封率为考察指标,采用正交试验法优选处方,并用透射电镜观察其形态,激光粒度仪测定粒径和Zeta电位,以超速离心法分离含药醇质体与游离药物,用HPLC法测定姜黄素醇质体的包封率.结果:优选处方为:姜黄素10 mg、蛋黄卵磷脂350 mg、胆固醇50 mg、乙醇百分浓度25%.实验所制醇质体纳米粒子为类球形囊泡结构,粒径为(210.8±2.0)nm,Zeta电位为(-3.49±0.27)mV,粒径分布均匀,多分散指数(PDI)为(0.144±0.006),以优选后处方制备醇质体,其包封率为(85.55±2.12)%.结论:乙醇注入法适用于姜黄素醇质体的制备,所制醇质体纳米粒子各项物理指标稳定,可用于经皮渗透给药的研究.     

Formulation development and systematic optimization of solid lipid nanoparticles of quercetin for improved brain delivery

Objective This study aims at formulating solid lipid nanoparticles (SLNs) of quercetin, a natural flavonoid with established antioxidant activity, for intravenous administration in order to improve its permeation across the blood–brain barrier into the CNS, and eventually to improve the therapeutic efficacy of this molecule in Alzheimer's disease. Methods The SLNs of quercetin were formulated using Compritol as the lipid and Tween 80 as the surfactant through a microemulsification technique, and optimized employing a 3² central composite design (CCD). Selection of the optimized SLN formulation, using brute‐force methodology and overlay plots, was based on its efficiency of entrapping quercetin inside the lipophilic core, particle size, surface charge potential and ability of the SLNs to release the entrapped drug completely. The optimized formulation was subjected to various in‐vivo behavioral and biochemical studies in Wistar rats. Key findings The optimized formulation exhibited a particle size of less than 200 nm, 85.73% drug entrapment efficiency and a zeta potential of 21.05 mV. In all the in‐vivo behavioral and biochemical experiments, the rats treated with SLN‐encapsulated quercetin showed markedly better memory‐retention vis‐à‐vis test and pure quercetin‐treated rats. Conclusions The studies demonstrated successful targeting of the potent natural antioxidant, quercetin, to brain as a novel strategy having significant therapeutic potential to treat Alzheimer's disease.     

黄豆苷元固体脂质纳米粒的制备及其性质考察

目的制备黄豆苷元固体脂质纳米粒并考察其性质。方法采用正交实验法优化黄豆苷元固体脂质纳米粒的最佳处方,并测定黄豆苷元固体脂质纳米粒的粒径、ζ电位、包封率、稳定性和累积释放百分率。结果黄豆苷元固体脂质纳米粒的最佳处方组合为：单硬脂酸甘油酯用量为2.0%,黄豆苷元用量为2.0 mg.mL-1,豆磷脂的用量为0.4%,Pluronic F68的用量为1.2%。所制得的纳米粒包封率为84.7%、平均粒径为170 nm、ζ电位为-35.8 mV、72 h累积释放百分率为90.3%。结论新制黄豆苷元固体脂质纳米粒的粒度分布范围窄,包封率较高,稳定性良好。     

Development and characterization of HBsAg-loaded Eudragit nanoparticles for effective colonic immunization

The present study was undertaken with an aim to investigate the potential of targeting colonic mucosa following oral vaccine delivery to generate prophylactic humoral and mucosal immune response. In present study, response surface methodology (RSM) using the central composite design (CCD) was applied for optimization of process and composition to get uniform, stable reproducible eudragit nanoparticles suitable for targeting to colon. The optimized formulation had the composition of 173?μg HBsAg, 250?mg polymers concentration (4:1 combination of Eudragit S-100 and L-100) and 2% w/v Polyvinyl alcohol (PVA) along with adjuvant Monophosphoryl lipid A (MPLA). Mean particle size of optimized nanoparticles was found to be 730.4?nm, entrapment efficiency (58.38%) and polydispersity index of 0.185. Fluorescent spectroscopy, differential scanning calorimetry, and antigen integrity by SDS-PAGE established that antigen structure was preserved during and after formulation development. In-vitro release studies in different intestinal pH concluded antigen release at mild alkaline conditions. Real time fluorescence animal imaging confirmed the effective absorption and distribution of NPs at colon resulted in improved immune response. Present study concludes that Eudragit nanoparticles offers strong potential in colon targeting of vaccines through oral immunization.     

醋酸布舍瑞林缓释纳米粒灭菌粉末的处方工艺研究及质量评价

目的:优化醋酸布舍瑞林缓释纳米粒(BA-PLGA-NP)灭菌粉末的处方,并评价其质量。方法:先对影响处方工艺的因素进行单因素试验,再在此基础上以包封率为考察指标,投药量、PLGA浓度、内水相-油相的体积比、超声功率为主要考察因素进行正交试验筛选最佳处方;同时考察其在4℃及-20℃条件下放置3个月的稳定性。结果:最佳处方为投药量0.5mg·mL-1、PLGA2.0%、内水相-油相体积比1∶10、超声功率40W;所制制剂粒径呈单峰分布,平均粒径为127～132nm,Zeta电位为-64.8～-67.3mV,包封率为(63.37±0.29)%。制剂在考察期内各指标均无明显变化。结论:该优化处方质量稳定,可行性较强。     

Brain targeted oral delivery of doxycycline hydrochloride encapsulated Tween 80 coated chitosan nanoparticles against ketamine induced psychosis: behavioral,biochemical, neurochemical and histological alterations in mice

To develop statistically optimized brain targeted Tween 80 coated chitosan nanoparticulate formulation for oral delivery of doxycycline hydrochloride for the treatment of psychosis and to evaluate its protective effect on ketamine induced behavioral, biochemical, neurochemical and histological alterations in mice. 3² full factorial design was used to optimize the nanoparticulate formulation to minimize particle size and maximize entrapment efficiency, while independent variables chosen were concentration of chitosan and Tween 80. The optimized formulation was characterized by particle size, drug entrapment efficiency, Fourier transform infrared, Transmission electron microscopy analysis and drug release behavior. Pure doxycycline hydrochloride (25 and 50?mg/kg, p.o.) and optimized doxycycline hydrochloride encapsulated Tween 80 coated chitosan nanoparticles (DCNP_opt) (equivalent to 25?mg/kg doxycycline hydrochloride, p.o.) were explored against ketamine induced psychosis in mice. The experimental studies for DCNP_opt, with mean particle size 237?nm and entrapment efficiency 78.16%, elucidated that the formulation successfully passed through blood brain barrier and exhibited significant antipsychotic activity. The underlying mechanism of action was further confirmed by behavioral, biochemical, neurochemical estimations and histopathological study. Significantly enhanced GABA and GSH level and diminished MDA, TNF-α and dopamine levels were observed after administration of DCNP_opt at just half the dose of pure doxycycline hydrochloride, showing better penetration of doxycyline hydrochloride in the form of Tween 80 coated nanoparticles through blood brain barrier. This study demonstrates the hydrophilic drug doxycycline hydrochloride, loaded in Tween 80 coated chitosan nanoparticles, can be effectively brain targeted through oral delivery and therefore represents a suitable approach for the treatment of psychotic symptoms.