双氯灭痛微囊的含量测定及体外溶出度观察

本文利用紫外分光光度法测定双氯灭痛微囊含量，并对双氯灭痛微囊及肠溶片进行体外溶出度测定比较。实验结果表明，双氯灭痛微囊与肠溶片Ｔ５０、Ｔ４比较具有显著差异（ｐ＜０．０５），表明双氯灭痛微囊具有明显的缓释作用，延长药物作用时间，这为其制备长效制剂提供了依据。     

海藻酸钠--氯化钡微囊牢固度和生物相容性的实验研究

目的 研究海藻酸钠—氯化钡微囊的牢固性、生物相容性。方法 以海藻酸钠和氯化钡为材料，采用气体吹喷制囊法制成微囊，将其置于生理盐水中37℃孵育2个月或置于生理盐水中37℃、150次／分水浴振荡1小时，观察微囊的破损率及形态改变。将5000个空微囊分别注射于12只大鼠腹腔内，于2、6、10周各取4只大鼠处死后用生理盐水灌洗腹腔，将灌洗液离心后计算其中空微囊数并观察微囊的形态改变。结果 海藻酸钠—氯化钡微囊在37℃培养箱孵育2个月，微囊破损率为10％；空微囊于37℃150次／分水浴振荡1小时，微囊破损率为18％；植入空微囊后第2周时腹腔灌洗，每只大鼠可洗出空微囊约3000个，微囊形状均呈圆形，完整，无纤维化；6～10周时每只大鼠可洗出空微囊约1000～1500个，其中50％～60％微囊形态完整，仍呈圆形，未见明显纤维化；20％～25％仍呈圆形，但纤维化明显；10％～15％微囊变形或有裂口，部分微囊有明显纤维化。结论 用海藻酸钠—氯化钡制成的微囊具有较好的牢固度及生物相容性。     

离心雾化法制备吲哚美辛微囊

采用自制的离心雾化设备制备了肠溶吲哚美辛微囊。对设备的性能和微囊的性质进行了考察，当雾化转速３５００～５５００ｒ·ｍｉｎ－１，供液速度５０ｍｌ·ｍｉｎ－１时，制得粒径１５０～３５０μｍ，产率＞７０％的微囊。微囊溶出速率与母液和接收器内囊材的性质有关。此方法简单，易操作，影响因素少。     

酮咯酸氨丁三醇微囊的研究

目的制备酮咯酸氨丁三醇的海藻酸钠-壳聚糖微囊，对其体外释药特性进行考察。方法采用滴液法制备微囊，以均匀设计优化制备工艺，溶出度测定法考察微囊体外释药特性。结果80％微囊粒径在200-250μm，微囊表面光滑圆整无粘连，包封率达90．56％，载药量达43．65％；微囊在人工胃液和蒸馏水中的释药规律符合Higuchi方程。结论酮咯酸氨丁三醇的海藻酸钠-壳聚糖微囊在人工胃液和蒸馏水中具有缓释作用。     

两种微囊化成猪胰岛体内体外功能的比较

目的：观察两种微囊化成猪胰岛体内，体外功能，明确两者间的优劣。方法：采用两种不同的免疫隔离材料对同一来源的成猪胰岛进行微囊化包裹，进行体外培养及四组糖尿病大鼠腹腔内移植。结果：（1）三组胰岛细胞培养液中胰岛素水平，除第6天时未微囊化组较海藻酸钠微囊化组和琼脂糖微囊化组胰岛素水平明显下降，有显著性差异（P＜0．05），余时相各组间无显著性差异；胰岛素刺激释放试验结果三组产无显著性差异。2）四组糖尿病大鼠胰岛移植前血糖水平无显著性差异，移植后1周时琼脂糖微囊化组和海藻酸钠微囊化相与未微囊化组和对照组相比均有显著性差异，且生存期明显长于后两组，但琼脂糖微囊化胰岛组的生存期明显短于海藻酸钠微囊化胰岛组（分别为平均57．10天和145．17天）。结论：两种包膜材料制备的微囊化成猪胰岛在体外具有相似的生物活性，均可存活于糖尿病大鼠体内发挥生物功能，但海藻酸钠微囊化胰岛组较琼脂糖微囊化胰岛组的存活期明显延长。     

共微囊血红蛋白对大鼠胰岛细胞功能的影响

目的：探讨共微囊血红蛋白(Hb)对大鼠胰岛细胞功能的影响。方法：用琼脂糖微囊包被大鼠胰岛或共同包被Hb体外培养，硝普钠(SNP)作为一氧化氮(NO)供体，放射免疫法检测培养液中胰岛素含量，比较共微囊化(含Hb)、单纯微囊化、未微囊化胰岛细胞胰岛素分泌功能。结果：无SNP培养液中，3种胰岛细胞之间胰岛素分泌量差异无显著性；含SNP培养液中，单纯微囊化、未微囊化胰岛细胞胰岛素分泌受到明显抑制；共微囊化胰岛细胞胰岛素分泌功能良好。结论：共微囊血红蛋白可拮抗NO对微囊内胰岛的损害，有利于维持胰岛的功能。     

海藻酸钠-聚左赖氨酸-海藻酸钠微囊包裹杂交瘤细胞的研究

目的对海藻酸钠-聚左赖氨酸-海藻酸钠(APA)微囊包裹杂交瘤细胞进行初步研究。方法用人IgG₁免疫小鼠，取免疫后脾细胞与小鼠骨髓瘤细胞系SP2/0细胞融合，获得分泌抗人IgGκ链单克隆抗体(mAb)的杂交瘤细胞株，命名为JY-A1；通过优化制备条件，制备包裹杂交瘤细胞的APA微囊，并考察形态学；比较不同微囊膜的机械强度和化学强度；用ELISA法测定mAb的释放。小鼠腹腔注射微囊，不同时间回收观察。结果相同条件下制得的微囊粒径均匀、表面光滑。体外培养条件下mAb能持续透过微囊膜。小鼠腹腔注射微囊后无异常，回收的微囊大部分形态完整。结论采用高压静电成囊技术制备的APA微囊具有较高的膜强度，对细胞分泌产物mAb能持续稳定释放，在小鼠体内有较好的生物相容性。     

微囊化技术在药物研究中的应用

药物微囊化技术是指将固态或液态药物包裹在天然或合成高分子材料中形成的直径1～5 000 μm的微小囊状物中的技术。目前解释药物微囊化释药规律的理论包括透过囊壁扩散释放药物、随着囊壁的溶解而释放药物、随着囊壁的消化降解而释放药物等。药物微囊化后，可提高其稳定性，减轻不良气味，防止药物在胃肠道内失活，减少药物对胃肠道的刺激性，缓释或控释药物的释放，使液体药物固化，便于制剂生产、贮存和使用，避免药物的配伍变化，使药物浓度集中于靶区，稳定其生物活性，有助于发挥疗效等。目前常用的微囊化技术包括基因工程细胞移植微囊化、生物分子类药物微囊化、微生态类药物微囊化、油类的微囊化等。     

阿克拉霉素癌微囊的研究(英文)

研究工作阐述了毫微囊的制备及冻干条件，并进行了毫微囊的再分散性实验，测定了毫微囊的粒度分布和药物包封率。家兔静脉注射阿克拉霉素Ａ毫微囊后，血药浓度表明其符合二室开放模型，与阿克拉霉素Ａ注射液相比，阿克拉霉素Ａ毫微囊在家兔体内的消除半衰期较长，（前者ｔ１／２（β）＝１０．２５ｈ，Ａｕｃ＝８１．８８ｍｇ／Ｌ·ｈ；后者ｔ１／２（β）＝１７．０４ｈ，Ａｕｃ＝１０６．７４ｍｇ／Ｌ·ｈ），而且阿克拉霉素Ａ包于聚氰基丙烯酸正丁酯毫微囊后改变了其在大鼠体内的组织分布。结果表明：阿克拉霉素Ａ在肺、胸腺、脾和小肠中浓度较高，而在心、肾、肝和大肠中浓度较低。     

头孢拉定－乙基纤维素微囊的研制

以乙基纤维素为包囊材料，采用油中干燥法制备了头孢拉定微囊，并对微囊的含量、粒度分布及释放速度等进行了研究。     

喷雾干燥法制备吡哌酸缓释微囊

用喷雾干燥法制备吡哌酸缓释微囊,以乙基纤维素作囊材,硬脂酸作阻滞剂,制备的微囊能明显延缓药物的释放。药物释放速率随其含量增加而增加,释药的表观扩散系数随微囊粒径降低而降低。家兔体内药物动力学研究结果表明,与片剂相比,吡哌酸微囊口服后,血药浓度维持时间较长。     

吡哌酸缓释微囊的体外溶出特性考察

考察了不同主药含量、不同粒径的吡哌酸缓释微囊的药物溶出特性及在不同pH介质中的溶出行为,探讨了微囊中吡哌酸含量对微囊结构、半数测出时间T_(50)及药物渗透性的影响与因不同pH介质中由于药物溶解度不同而引起的溶出行为的改变。证实了微囊释药符合Higuchi方程,其结构与药物含量有关,药物渗透性及T_(50)~(1/2)与药物含量存在线性相关性,药物溶出因微囊粒径减小、药物于介质中溶解度增加而增加。     

尼莫地平缓释片的制备及稳定性的初步考察

用尼莫地平和高分子化合物制成固体分散体压制片剂，研究了释放性能和稳定性。结果表明释放呈溶蚀型模式，释药速度变慢，而且稳定性较好。     

油中干燥法制备甘氨酸茶碱钠微囊及其释药特性的研究

采用油中干燥法，以ＥｕｄｒａｇｉｔＲＳ１００和Ｅｕｄｒａｇｉｔ ＲＬ１００为囊材制备水溶性药物甘氨酸茶碱钠微囊。实验结果表明，所得微囊能延缓药物的释放，且以ＥｕｄｒａｇｉｔＲＳ１００为囊材制得到的微囊缓释性能较优。     

尼莫地平胃内滞留漂浮型缓释片的研究

将尼莫地平先制成速释型固体分散体,再压制成胃内滞留漂浮型缓释片(NM-FSRT)。均匀设计法优选处方,并考察处方因素对尼莫地平释放的影响,在人体内对NM-FSRT进行了初步评价。结果表明优选处方于体外漂浮达10h,0.15～6h释放符合零级动力学。HPMC量越大,药物释放越慢,PEG 6000量越大,释放越快。饮食后NM-FSRT于胃内滞留时间约5h,空腹时约3h;对照非漂浮片饭后服滞留时间为3h,空腹2h排空。体内相对生物利用度为391.46%,MRT较普通片延长一倍多。     

尼莫地平渗透泵型控释片的研制及释药影响因素考察

目的制备中剂量难溶性药物尼莫地平单室渗透泵型控释片 ,并考察其释药机理及影响释药因素 ,探讨药物释药规律。方法单因素考察影响释药的因素。结果制备了中剂量难溶性药物尼莫地平单室渗透泵型控释片 ;氯化钠、阿拉伯树脂胶、衣膜厚度及增塑剂的用量是影响释药的主要因素。结论尼莫地平单室渗透泵型控释片工艺稳定 ,能够达到 12h明显的恒速释药     

Evaluation of the Properties of Ethylcellulose-Cellulose Triacetate Microcapsules Containing Theophylline Prepared by Different Microencapsulation Techniques

Abstract

Using cellulose triacetate as an added complementary coating material in preparing sustained-release ethylcellulose-cellulose triacetate microcapsules of theophylline, three microencapsulation techniques were investigated. Ethylcellulose-cellulose triacetate composite microcapsules, ethylcellulose-cellulose triacetate dual-walled microcapsules and ethylcellulose microcapsules containing cellulose triacetate matrices were prepared using the non-solvent addition phase separation method. The effects of cellulose triacetate on the release of theophylline from the different ethylcellulose-cellulose triacetate microcapsules were obtained from dissolution studies. The results showed that the release rates of ethylcellulose-cellulose triacetate microcapsules were slower than those obtained from the ethylcellulose microcapsules prepared with similar core to wall ratios. The ethylcellulose microcapsules containing cellulose triacetate matrices had longer release half-times and smaller surface areas than the other capsule preparation. The release patterns of theophylline from the different ethylcellulose-cellulose triacetate microcapsules fitted first-order kinetics. Scanning electron micrographs showed that the surfaces of various ethylcellulose-cellulose triacetate microcapsules were different from those of theophylline, cellulose triacetate matrices of cellulose triacetate microcapsules, and that the surface morphology of ethylcellulose-cellulose triacetate microcapsules was affected by the preparative method.     

更昔洛韦肺部靶向微囊的制备及体外释放度测定

目的:制备更昔洛韦肺部靶向微囊并测定其体外释放度。方法:以双乳化溶剂挥发法制备微囊;采用紫外分光光度法测定微囊的体外释药量,考察其体外释放度。结果:所制微囊外观圆整,平均粒径13.87μm;更昔洛韦检测浓度的线性范围为2～20μg·mL-1(r=0.999 9),平均回收率为99.96%(RSD=1.68%);包封率为63.85%,24h累积体外释放度约为40%。结论:更昔洛韦肺部靶向微囊具有良好的缓释性。     

Layer-by-layer assembly of poly(l-glutamic acid)/chitosan microcapsules for high loading and sustained release of 5-fluorouracil

Hollow polyelectrolyte microcapsules based on poly(l-glutamic acid) (PLGA) and chitosan (CS) with opposite charges were fabricated by layer-by-layer (LbL) assembly technique using melamine formaldehyde (MF) microparticles as sacrificial templates. The LbL assembly of polyelectrolytes and the resultant PLGA/CS microcapsules were characterized. A hydrophilic anticancer drug, 5-fluorouracil (5-FU), was chosen to investigate the loading and release properties of the microcapsules. The PLGA/CS microcapsules show high loading capacity of 5-FU under conditions of high drug concentration and salt adding. The high loading can be ascribed to spontaneous deposition of 5-FU induced by hydrogen bonding between 5-FU and PLGA/CS microcapsules. The PLGA/CS microcapsules show sustained release behavior. The release rate of 5-FU drastically slows down after loading in PLGA/CS microcapsules. The 5-FU release from PLGA/CS microcapsules can be best described using Ritger-Peppas or Baker-Londale models, indicating the diffusion mechanism of 5-FU release from the PLGA/CS microcapsules. In vitro cytotoxicity evaluation by the MTT assay shows good cell viability over the entire concentration range of PLGA/CS microcapsules. Therefore, the novel PLGA/CS microcapsules are expected to find application in drug delivery systems because of the properties of biodegradability, high loading, sustained release and cell compatibility.     

Oral controlled release formulation of diclofenac sodium by microencapsulation with ethyl cellulose

The aim of this study was to formulate and evaluate microencapsulated controlled release preparations of diclofenac sodium (DFS) using different proportions of ethyl cellulose (EC) as the retardant material to extend the release. The formulated microcapsules were then compressed into tablets to obtain controlled release oral formulations. Phase separation-coacervation technique was employed to prepare microcapsules of DFS using different proportions of EC in cyclohexane. Physical characteristics of microcapsules and their tablets, in vitro release pattern of the designed microcapsules and their tablets prepared from them were studied using USP dissolution apparatus (USP 2000) type 2 (paddle method) in triple distilled water. The prepared microcapsules were white, free flowing and spherical in shape, with the particle size varying from 49.94-52.72 #119 m. The duration of DFS release from microcapsules was found to be directly proportional to the proportion of EC and, thus, coat thickness. All tablets were of good quality with respect to appearance, drug content uniformity, hardness, weight variation, friability and thickness uniformity. In vitro release study of the tabletted microcapsules in triple distilled water showed a zero order release kinetics and extended release beyond 24 h. A good correlation was obtained between drug release (t 60) and proportion of EC in the microcapsules. In the case of tabletted microcapsules, very good correlation could be established between t 60, proportion of EC, weight of the tablets and between release rate constant (K) and proportion of EC. All the formulations were highly stable and possessed reproducible release kinetics across the batches.