去氢骆驼蓬碱脂质体的制备和体外释放特性

目的：研究去氢骆驼蓬碱（harmine,HM）脂质体的制备工艺和体外释放特性。方法：运用薄膜分散-pH值梯度法制备HM．脂质体以及高速离心法分离脂质体与游离药物,并测定其包封率;借助综合评分法,评价其粒径、多分散系数、包封率、载药量指标;运用正交优化实验法考察磷脂-胆固醇与药-脂比、超声时间、外相pH值对脂质体的影响,述选最优工艺处方,评价脂质体与原料药的体外释放情况。结果：最优处方因素为磷脂-胆固醇比值为4：1,超声时间为300S,药-脂比值为1：5,外相pH值为6,8,即X13X23X32X43,经实验验证其粒径为（155.0±14．5）nm,多分散系数为（0．148±0．011）,包封率为（80．90±0．01）％,载药量为（11．16±0．01）％;其原料药0．5h累积释放百分比大于50％,不到2h已全部释放,而优化后的脂质体在1h内其累积释放百分比大于50％,4h后释放完成。结论：采用薄膜分散-pH值梯度法,以最优处方制得HM-脂质体,其粒径大小适中、形态均匀,包封率和载药量相对较高,体外释放显示具有较好的缓释特性。     

头孢匹胺钠脂质体的制备及其理化性质研究

目的：制备头孢匹胺钠脂质体并进行质量评价。方法：采用逆相蒸发法制备头孢匹胺钠脂质体,在单因素考察基础上,以药脂比（A）、磷脂与胆固醇质量比（B）、有机相（乙醚）与水相体积比（C）、超声时间（D）为因素,以包封率为考察指标,按Lq（3‘）正交试验设计表优化最佳处方和工艺,并进行处方验证;考察脂质体的形态,测定其粒径、Zeta电位、包封率、栽药量和72h体外累积释放度并进行模型拟合。结果：正交试验设计优化的A为1：6、B为5：1、C为4：1、D为5min,验证试验证明处方合理;所得的脂质体为封闭的多层囊状或圆球体,大小均匀,平均粒径为（7．146±O．29）gm,Zeta电位为一11．75mV,包封率为（82．10±4．21）％,载药量为（愠42±O．67）％;72h体外累积释放度为76．84％,体外释药行为符合We~bull模型（r=0．9910）。结论：采用逆相蒸发法制备的头孢匹胺钠脂质体,包封率较高,体外释药有明显的缓释效果。     

川芎嗪脂质体的制备和质量评价

目的：制备川芎嗪脂质体，考察其理化性质。方法：以磷脂-胆固醇（2．5：1．5）为包封膜材，采用注入乳匀法制备川芎嗪脂质体，观察脂质体形态，测定其粒径，采用HPLC法测定川芎嗪含量，并考察其包封率、载药量和稳定性。结果：川芎嗪脂质体平均粒径为200nm，包封率和载药量分别为（39．5±0．66）％和（0．719±0．011）％。4℃保存30d稳定。结论：以本方法制备的川芎嗪脂质体质量符合《中华人民共和国药典》的要求。     

青蒿素脂质体的制备及质量评价

目的通过对青蒿素脂质体的处方和制备工艺研究,研制高包封率和稳定的脂质体。方法采用乙醇注入法制备脂质体,以正交实验优化处方。测定了脂质体中药物的包封率;并初步考察了脂质体的稳定性。结果优化处方与工艺所得脂质体形态均匀,包封率〉85％,载药量达27．22％,粒径约为90nm,Zeta电位约为一68．4mV,具有良好的稳定性。结论乙醇注入法制备脂质体工艺简便,包封率高,制备的脂质体稳定性好。     

载环孢素纳米球的制备及释放特性*

目的：制备一种环孢素A（CsA）缓释纳米体系。方法：以PLA-co-PEG共聚物材料作为环孢素药物的释放载体；采用超声振荡技术制备载环孢素的PLA—PEG—PLA纳米球；分析纳米球的粒径与分布以及纳米球降解过程中的形貌变化；体外释放试验探讨制备的纳米球的降解特性以及与载体材料、介质pH值之间的影响关系；小鼠灌胃后HPLC法测定血药浓度。结果：采用PLA—PEG—PLA共聚材料装载CsA，药物包封率达到89．2％。纳米球平均粒径为242．3nm，载药后平均粒径增大到320．2nm。扫描电镜分析发现纳米球在磷酸缓冲液中溶胀程度与降解速率依赖于介质pH值。体外模拟释放表明载药纳米球的药物释放速率与载体降解速率一致，持续稳定释药时间〉7d。动物模型也证实该载CsA纳米球可维持血液中稳定的药物浓度5d以上。结论：利用本方法制备的载CsA纳米球是一种较理想的环孢素药物剂型，具有临床应用价值。     

载环孢素A海藻酸钙-壳聚糖微球的制备及体外释放特性

目的:针对角膜移植术后免疫抑制治疗需求,制备眼部局部给药的小粒径载环孢素A缓释微球,并进行体外释放考察。方法:以海藻酸钠、壳聚糖为载体材料,采用静电液滴工艺,通过向制备体系添加表面活性剂,制备小粒径载环孢素A微球,设计正交试验优化处方工艺,扫描电镜观察微球表面形态,动态透析法考察微球的体外释放特性。结果:所制微球形态良好,粒径分布窄,平均粒径为(12.4±0.8)μm,包封率为(82.8±1.8)%,载药量为(50.1±1.2)%,体外释放行为用Higuchi方程拟合效果最好。结论:采用静电液滴工艺,通过减小制备体系的表面张力,制备了球形度优良、粒径小、包封率和载药量较高的载环孢素A的壳聚糖-海藻酸盐缓释微球,所得制剂的体外释药规律服从扩散机制。     

他克莫司纳米微球的制备及其体外释药性能

目的采用甲氧基聚乙二醇-聚乳酸聚合物（PEG—PLA）制备他克莫司微球（PPT），研究其体外释药特性。方法考察PPT的载药量、包封率、粒径大小、粒径分布和药物体外释放实验。结果PPT的制备工艺稳定、重复性好，微球外形圆整，表面光滑，分布均匀，平均粒径为（545．1±0．9）nm，平均载药量为（18．90±3．22）％，平均包封率为（25．0±1．6）％，35d的药物累积释放率为67．21％。结论他克莫司微球缓释时间长达35d，能够满足临床治疗的要求。     

离子载体A23187介导pH梯度法制备重酒石酸长春瑞滨长循环脂质体

目的:采用A23187制备重酒石酸长春瑞滨长循环脂质体,优化了处方工艺,并考察了含量、包封率、药脂比和体外释放等检测指标。方法:采用A23187介导的pH梯度法制备了重酒石酸长春瑞滨脂质体;用HPLC法检测了脂质体中重酒石酸长春瑞滨的含量和脂质(HSPC)的含量,考察了药脂比;采用阳离子交换树脂分离脂质体和游离药物,HPLC法检测包封率;以4 mmol.L-1NH4Cl-PBS(pH 7.4)为体外释放介质考察了脂质体的体外释放行为。结果:重酒石酸长春瑞滨脂质体包封率为96.1%,药脂比为1∶5(w/w);高药脂比有利于延长药物体外释放的时间。结论:采用A23187介导的pH梯度法制备重酒石酸长春瑞滨脂质体工艺可行、载药量大、包封率高;所建立体外释放的检测方法快速、准确。     

去氢骆驼蓬碱聚合物胶束的制备工艺优化及体外释放的研究

目的：研究星点设计-响应面法优化去氢骆驼蓬碱N-癸酰-N-三甲基壳聚糖胶束（harmine loaded N-Decanoate-N-trimethyl chitosan micelles,HM-De-TMC-MIC）的处方优化,并考察在不同介质中HM-De-TMC-MIC的体外释放。方法：以薄膜分散法制备HM-De-TMC-MIC;以粒径、多分散系数、包封率和载药量为指标,通过单因素考察和星点设计-响应面法综合考察药物与载体质量比和复水体积对HM-De-TMC-MIC的影响,并遴选其最优处方。在不同pH的释放介质中,分别考察HM-De-TMC-MIC和HM的体外释放。结果：筛优处方药物与载体质量比为3.6∶10,复溶水体积为6 mL;以最优处方制备的HM-De-TMC-MIC粒径为（148.2±5.0）nm,多分散系数为0.198±0.045,包封率（89.80±0.19）%,载药量（22.79±0.05）%,形态圆整。体外释放试验结果表明,HM-De-TMC-MIC的释放曲线遵循Higuchi方程,与HM溶液相比其释放较为缓慢,并呈现pH敏感释药行为。结论：以星点设计-响应面法优化的HM-De-TMC-MIC具有较好包封率和载药量,粒径分布均匀,具有明显的缓释性。     

响应面法优化依托泊苷脂质体制备工艺的研究

目的制备依托泊苷脂质体并考察其药剂学性质。方法采用薄膜水化．高压均质法制备依托泊苷脂质体,以胆固醇与氢化磷脂的摩尔比（A）、脂质体溶液中的磷脂浓度（B）、依托泊苷与氢化磷脂的质量比（C）为考察因素,以包封率（y1）、载药量（y2）、综合指标（y3）为响应值,经Box—Behnken效应面法（respon sesurface methodology,RSM）进行处方优化,得到最优处方,并测定脂质体的粒径。结果经RSM优化后,A、B、C分别为0．49,4．96％,0．15;制得的依托泊苷脂质体实测包封率为82．6％,裁药量为11．4％,平均粒径为132．5nm。结论利用Box．Behnken效应面法优化依托泊苷脂质体处方,能制备符合药剂学要求的脂质体,可供体内实验研究。     

促进环孢素A大鼠肠道吸收的机制与剂型因素研究

目的:考察促进环孢素A(cyclosporine A,CsA)肠道吸收的机制及其剂型因素。方法:与CsA胶囊(商品名:新山地明,Neoral)为对照,比较CsA脂质体(cyclosporine A-liposome,CsA-Lip)、环孢素-A-EudragitL100纳米粒(cyclosporine A-Eudragit L100-nanoparticles,CsA-L100-NP)和环孢素A-Eudragit S100纳米粒(cyclosporine A-Eudragit S100-nanoparticles,CsA-S100-NP)以及吸收促进剂,如去氧胆酸钠(SDCh)、十二烷基磺酸钠(SDS)、泊洛沙姆(poloxamer)和羟丙基-环糊精(HP-β-CD)等在大鼠肠道各段透膜的促吸收机制及其影响因素。结果:CyA-Lip和Neoral在十二指肠、空肠的通透系数显著大于CsA-L100-NP和CsA-S100-NP(P<0.05);回肠中CsA-Lip的通透系数明显大于Neoral、CsA-L100-NP和CsA-S100-NP(P<0.05),而3种制剂之间的吸收速率差异无统计学意义(P>0.05)。结论:CsA-Lip具有更明显的促进吸收作用。     

含碳酸氢铵羟基喜树碱粉雾剂的研制

目的:提高10-羟基喜树碱(HPCT)粉雾剂的沉积性能。方法:利用喷雾干燥法制备HPCT粉雾剂,考察处方中加入碳酸氢铵后粉末的密度、比表面积、表面形态、粒度及体外沉积性能。结果:制备出了敲击密度为0.015g·mL-1、比表面积为19.81m2·g-1、体积平均直径为15.64μm的粉末,该低密度、大粒径的多孔性粉粒大大提高了药物的体外沉积性能,粉雾剂的体外沉积率由18.0%提高至51.6%。结论:加入碳酸氢铵能够显著提高HPCT粉雾剂的沉积性能。     

In vitro performance of two common valved holding chambers with a chlorofluorocarbon-free beclomethasone metered-dose inhaler

STUDY OBJECTIVE: To compare in vitro aerosol deposition from a beclomethasone dipropionate metered-dose inhaler (MDI) containing hydrofluoroalkane propellant with that of the MDI in combination with two common valved holding chambers (VHCs) to evaluate how these VHCs affect the respirable dose of beclomethasone dipropionate. DESIGN: In vitro aerosol deposition study. SETTING: University research center. DEVICES: Beclomethasone dipropionate hydrofluoroalkane MDI alone, the MDI with OptiChamber VHC, and the MDI with AeroChamber-Plus VHC. INTERVENTION: The respirable dose (1-5-microm aerosol particles) of beclomethasone dipropionate was determined by sampling 10 80-microg actuations from five runs with each configuration (MDI alone, MDI with OptiChamber, and MDI with AeroChamber-Plus), using a well-established in vitro cascade impactor method. MEASUREMENTS AND MAIN RESULTS: Beclomethasone dipropionate aerosol was washed from the impactor with 50% methanol and quantified by means of high-performance liquid chromatography. Differences among outcomes were determined by using analysis of variance. Mean beclomethasone dipropionate respirable dose from AeroChamber-Plus (27.2 +/- 10.0 microg/actuation) was not significantly different (p>0.05) from that of the MDI alone (29.0 +/- 7.0 microg/actuation). OptiChamber respirable dose (12.8 +/- 6.0 microg/actuation) was less than half that produced by either the AeroChamber-Plus or the MDI alone (p=0.013). CONCLUSIONS: The OptiChamber and AeroChamber-Plus VHCs do not demonstrate equivalent in vitro performance when used with a beclomethasone dipropionate MDI that contains hydrofluoroalkane propellant. The respirable dose of beclomethasone dipropionate aerosol from the hydrofluoroalkane MDI was decreased by only 6% when the MDI was mated to an AeroChamber-Plus VHC and by 56% when used with an OptiChamber VHC.     

国外重组人红细胞生成素产品的体内外生物学活性测定

目的 :用WHO提供的红细胞生成素 (EPO)生物学活性国际标准品 ,测定国外重组人红细胞生成素(rhEPO)产品的体内外生物学活性 ,并比较其差异 ,探讨作为工作标准品的可能性。方法 :网织红法测定rhEPO体内生物学活性 ,ELISA法测定体外生物学活性。结果 :生血素、利血宝的体内生物学活性分别为 1880、2 986IU/瓶 ,体外生物学活性分别为 1867、2 880IU/瓶。结论 :国外rhEPO产品体内、体外生物学活性较一致 ,但与标示量有一定差距 ,需经标定后才能作为EPO产品的体内生物学活性标准。     

黄连总生物碱胃内漂浮缓释片处方组成的研究

目的：研究黄连总生物碱胃内漂浮缓释片的处方组成及影响因素。方法：以体外释放度为指标,筛选黄连总生物碱胃内漂浮缓释片的处方组成,采用单因素试验法,考察处方中HPMC、海藻酸钠、碳酸氢钠三个因素对其体外释放度的影响。结果：黄连总生物碱胃内漂浮缓释片较优的处方组成为HPMC13.4%,海藻酸钠26.6%,硬脂酸镁5.4%,硬脂酸42%,碳酸氢钠10.6%,HPMC与碳酸氢钠的用量显著影响黄连总生物碱胃内漂浮缓释片的体外释放度。结论：HPMC与海藻酸钠以1：2配伍使用作为片剂亲水凝胶骨架时,其体外释放度良好,且两者具有交互作用。     

单硝酸异山梨酯渗透泵型控释片的制备及体外释药机制考察*

目的:制备单硝酸异山梨酯渗透泵型控释片(ISMN-OPT)并考察其体外释药机制。方法:制备了IS- MN-OPT;通过以不同渗透压和不同pH值的溶液为体外释药介质、不同溶出仪转速为释放条件,进行体外释放试验,考察ISMN-OPT的释药机制。结果:制备的3批ISMN-OPT,18h内体外释放曲线拟合符合零级过程。结论:IS- MN-OPT主要以渗透泵机制释放,所制备的ISMN-OPT,工艺稳定,能达到最初设计要求。     

醋酸地塞米松眼用凝胶剂的制备与质量控制

目的: 制备醋酸地塞米松凝胶剂,考察其质量与体外释放的特征.方法: 以醋酸地塞米松为主药,卡波谱为凝胶基质,制备醋酸地塞米松眼用凝胶剂,用紫外分光光度法测定其含量,用透析法考察其体外释放行为.结果: 醋酸地塞米松凝胶剂中醋酸地塞米松的平均含量为标示量的99.51%,RSD1.43%.透析实验考察一周,平均释药百分率为68.26%.结论: 该凝胶剂制备简单,性质稳定,质量可控, 释放时间延长.     

格列齐特缓释片的研制及体外释放度考察

目的;制备格列齐特缓释片并考察其体外释放度。方法采用混合骨架材料制备格列齐特缓释片;参照进口格列齐特缓释片标准,采用紫外分光光度法,以pH7.4磷酸盐缓冲液900ml为溶剂,桨法测定本品释放度,并与参比制剂进行比较。结果所得缓释片体外释放度符合一级动力学规律,释放曲线经相似因子(f2)判断,与参比制剂相似。结论本品处方工艺稳定、重现性好,体外累积释放度符合要求。     

Kinetic Analysis on the Skin Disposition of Cytotoxicity as an Index of Skin Irritation Produced by Cetylpyridinium Chloride: Comparison of In Vitro Data using a Three-Dimensional Cultured Human Skin Model with In Vivo Results in Hairless Mice

PURPOSE: The aim of this study was to kinetically and dynamically analyze in vitro cytotoxicity as an index of skin irritation by use of a three-dimensional cultured human skin model and to compare the in vitro assay data with data from living animals. METHODS: A cationic surfactant, cetylpyridinium chloride (CPC), was selected as a model irritant. Living skin equivalent-high (LSE-high) and hairless mice were used for the in vitro and in vivo tests, respectively. Skin irritation dermatodynamics was evaluated by calorimetric thiazoyl blue (MTT) conversion assay both for in vitro and in vivo tests, whereas dermatokinetics of CPC in LSE-high and mouse skin were evaluated using HPLC. RESULTS: The time course of cell viability in the skin after application of CPC to intact skin was distinctly different from that of stratum-corneum-stripped skin in both LSE-high and hairless mice. Biphasic behavior characterized by two first-order rates with an inflection time point was observed in intact skin, whereas cell viability monoexponentially decreased immediately after CPC application in stripped skin. The time courses of cell viability in the skin and dermatodynamics were closely related to that of dermatokinetics of CPC. CONCLUSION: The present study demonstrates that the in vitro cytotoxic profile was similar to the in vivo cytotoxicity test and that dermatodynamics was related to dermatokinetics of CPC.     

<Emphasis Type="BoldItalic">In Vitro</Emphasis> and <Emphasis Type="BoldItalic">In Vivo</Emphasis> Release of Vascular Endothelial Growth Factor from Gelatin Microparticles and Biodegradable Composite Scaffolds

PURPOSE: This work evaluated gelatin microparticles and biodegradable composite scaffolds for the controlled release of vascular endothelial growth factor (VEGF) in vitro and in vivo. METHODS: Gelatin crosslinking, VEGF dose, and buffer type were investigated for their effects on VEGF release. Release was also evaluated from microparticles confined within porous polymer scaffolds (composites). In vitro and in vivo studies were conducted using radiolabeled VEGF. RESULTS: The effect of VEGF dose on its fractional release from gelatin microparticles in vitro was minimal, but the addition of collagenase to the buffer resulted in a higher cumulative release of VEGF. Gelatin crosslinking extent was a significant factor on release from both microparticles alone and composite scaffolds in vitro and in vivo. VEGF bioactivity from composite scaffolds in vitro was maintained above 90% of the expected bioactivity over 14 days. CONCLUSIONS: VEGF release kinetics were dependent on the extent of gelatin crosslinking and were characteristic of the specific growth factor due to the effects of growth factor size, charge, and conformation on its complexation with gelatin. These studies demonstrate the utility of gelatin microparticles and their composite scaffolds as delivery vehicles for the controlled release of VEGF for tissue engineering applications.