双氯芬酸钠/海藻酸钠微球的制备与体外释药行为考察

目的以海藻酸钠为载体材料,双氯芬酸钠为模型药物,制备载药微球并考察其性质及体外释放行为。方法本文采用海藻酸钠为药物载体,采用喷雾干燥法制备双氯芬酸钠/海藻酸钠微球。考察于双氯芬酸钠/海藻酸钠投料比对载药微球理化性质的影响。采用扫描电镜对所得到的微球进行形貌观察。同时考察其体外药物释放行为。结果所得到的载药微球形态呈不规则的扁平状,粒径分布较为均匀。通过控制投料比,可以得到不同粒径(5.64～9.58μm),载药量(5.76～18.43%)和包封率(35.45～43.92%)的载药微球。体外药物释放行为结果显示微球在含有0.5%氯化钙的PBS(pH=7.4)溶液的药物释放时间可以持续96h,具有一定的缓释效果。结论通过喷雾干燥法制备的双氯芬酸钠/海藻酸钠载药微球具有较高载药量和一定的药物缓释效果。     

奥沙普秦壳聚糖-海藻酸钠缓释微球的制备

目的：目的：选择奥沙普秦作为模型药制备壳聚糖-海藻酸钠缓释微球。方法：采用滴制法制备奥沙普秦壳聚糖-海藻酸钠缓释微球，通过正交试验设计优化了处方和工艺，考察其理化特征及体外释药行为。结果：优化处方制得的微球包封率及载药量分别为98．36％和16．26％，平均粒径为（346．6±164．1）μm；1h药物释放达到36％，随后药物的释药行为是一个缓释过程。结论：制得了载药量较大，包封率较高的奥沙普秦壳聚糖-海藻酸钠缓释微球。     

吸附和包埋法制备洛美沙星淀粉微球及其体外释放比较研究

目的制备盐酸洛美沙星淀粉微球,并对其体外释药模式进行研究。方法以盐酸洛美沙星为模型药物,采用吸附载药法和包埋载药法制备了载药淀粉微球,通过测定微球载药量、包封率和在不同的释放介质中的体外释放情况,对上述2种方法制备的载药微球进行质量评价。结果吸附法制备的载药微球的平均载药量为14.54μg·mg^-1,药物包封率为39.72%;而包埋载药法制备的淀粉微球的平均载药量为19.32μg·mg^-1,药物包封率为48.95%。体外释药特性研究表明它们具有缓释特性,其中包埋载药法制备的淀粉微球比吸附载药法制备的淀粉微球有更好的缓释能力,在不同的释放介质中释药曲线也有所不同,在模拟胃液中累计释药量只能得到70%;而在模拟肠液中累计释药量能达到80%以上。结论吸附载药法和包埋载药法制备的载药淀粉微球都具有缓释作用,但后者体外释药具有更明显的缓释效果。     

长春西汀聚乳酸-聚乙醇酸缓释微球的研制

目的:制备长春西汀聚乳酸-聚乙醇酸(PLGA)缓释微球,并研究其药剂学性质。方法:采用改良O/W乳化-溶剂挥发法制备微球,以PLGA浓度、理论载药量、有机相与分散介质的比例和分散介质中明胶的浓度为4因素,每个因素选定3个水平,按L9(34)的正交设计方案,以载药量、包封率和粒径分布为指标,优化处方。用扫描电镜观察微球的形态,用光学显微镜观察并计算微球的粒径分布,用差示扫描量热(DSC)法研究药物在载体中的分散状态,用紫外分光光度法检测微球中长春西汀含量并计算载药量和包封率,用动态透析释药法进行微球的体外释放研究。结果:最佳处方为PLGA浓度16%,理论载药量20%,有机相与分散介质的比例1:10,分散介质中明胶的浓度1%;制备的长春西汀PLGA缓释微球的形态圆整、光滑,粒径分布均匀,平均粒径为(10.0±0.18)μm(n=500),DSC法分析药物确已被包裹于微球中,载药量为(18.46±0.26)%,包封率为(91.30±0.98)%(n=3),24h累积释药率约为18%。结论:长春西汀PLGA缓释微球制备工艺稳定,质量符合药剂学要求,缓释性好。     

吸附和包埋法制备洛美沙星淀粉微球及其体外释放比较研究

目的 制备盐酸洛美沙星淀粉微球,并对其体外释药模式进行研究。方法 以盐酸洛美沙星为模型药物,采用吸附载药法和包埋载药法制备了载药淀粉微球,通过测定微球载药量、包封率和在不同的释放介质中的体外释放情况,对上述2种方法制备的载药微球进行质量评价。结果 吸附法制备的载药微球的平均载药量为14.54 µg·mg^-1,药物包封率为39.72%;而包埋载药法制备的淀粉微球的平均载药量为19.32 µg·mg^-1,药物包封率为48.95%。体外释药特性研究表明它们具有缓释特性,其中包埋载药法制备的淀粉微球比吸附载药法制备的淀粉微球有更好的缓释能力,在不同的释放介质中释药曲线也有所不同,在模拟胃液中累计释药量只能得到70%;而在模拟肠液中累计释药量能达到80%以上。结论 吸附载药法和包埋载药法制备的载药淀粉微球都具有缓释作用,但后者体外释药具有更明显的缓释效果。     

可溶性甲壳素/海藻酸钠交联微球的制备及其表征和控释性能考察

目的制备可溶性甲壳素/海藻酸钠交联微球,表征微球的微观结构和形态。方法利用滴入法制备可溶性甲壳素/海藻酸钠交联微球,用红外光谱和扫描电镜表征微球的微观结构和形态,以牛血清蛋白为药物模型,研究微球的药物缓释性能。结果可溶性甲壳素与海藻酸钠进行了良好的混溶,并且在钙离子（Ca2+）溶剂环境下形成交联微球。该微球对药物的包封率及缓释性能与海藻酸钠微球相比都有较大改善,包封率从42%提高到74%,药物缓释时间从4 h上升到24 h。结论可溶性甲壳素/海藻酸钠微球的释药具有pH响应性,在pH为1.2的条件下释药慢,而在pH为7.0～7.4时释药快,可用于小肠或结肠定位缓释系统。     

载药蒙脱石/丙烯酸树脂微球的制备与体外释放性能的研究

目的以丙烯酸树脂为膜材制备载药蒙脱石/丙烯酸树脂微球并考察其体外释放性能。方法以盐酸倍他洛尔为模型药物,采用O/O溶剂挥发法制备蒙脱石载药微球,通过正交实验设计,考察柠檬酸三乙酯及甘油用量、乳化剂与膜材比例及用量、内外相体积比等因素对微球载药量、包封率、体外释放性能的影响,采用扫描电镜对其外观形态进行表征。结果所得微球外观圆整,粒径分布较均匀,平均粒径为20.7μm,平均载药量为14.31%±0.47%,平均包封率为94.35%±1.01%。结论该法制备载药蒙脱石丙烯酸树脂微球是可行的,体外释放研究表明微球具有一定的缓释作用。     

海洋多糖BTH缓释微球的制备及释放特性研究

目的 以海藻酸钠与壳聚糖为载体材料制备苯并[l,2,3]噻二唑-7-硫代羧酸甲酯(BTH)缓释微球并研究其释放特性。 方法 采用乳化-外源凝胶法制备BTH缓释微球,通过傅里叶变换红外光谱(FT-IR)验证BTH包封于微球当中,利用高效液相(HPLC)外标法测定微球的包封率、载药量以及不同pH溶液中的释放曲线。结果 BTH被均匀的分散在缓释微球当中,平均载药量为11.14%,平均包封率为81.52%,微球可持续释放12天,累计释放量达到61%。 结论 制备的BTH缓释微球形态圆整,表面光滑,成球性好,载药量与包封率较高,具有显著的缓释效果。     

球结膜下注射用西罗莫司缓释微球的制备及其体外释药性能

目的使用3-羟基丁酸-co-3-羟基戊酸共聚物制备西罗莫司缓释微球,为预防和治疗角膜移植术后免疫排斥反应奠定基础。方法采用乳化-溶剂挥发法制备微球,正交实验法优化,测得载药量、包封率等指标,结合光镜观察其形态特征,得出最佳制备条件后,模拟眼内前房环境检测其体外释药性能。结果微球制备工艺稳定,重复性好。微球成球率高,形态圆整,表面光滑,载药量为(37.34±1.25)%,包封率为(99.63±0.93)%,能够在体外稳定缓释,500 h累积释药率为71%。结论西罗莫司缓释微球表征良好,载药量、包封率较高,有望发挥稳定释药的临床作用。     

一种聚乳酸聚乙醇酸缓释微球的制备工艺

目的:研究一种制备聚乳酸聚乙醇酸(PLGA)微球的新工艺,即将海藻酸钠与钙离子螯合形成缓释凝胶的原理与复乳法制备微球的工艺相结合。方法:以牛血清白蛋白(BSA)为模型药,以包封率、载药量、产率作为评价指标,研究PLGA黏度、海藻酸钠浓度及外水相1中氯化钙浓度对微球性质的影响,并通过L9(34)正交试验设计优选微球制备的工艺条件。结果:优选的制备工艺重现性好,微球形态圆整,结构致密,平均粒径为67.5μm,载药量、包封率和产率分别为0.669%、53.38%和80.08%。结论:本研究获得了较为满意的制备PLGA微球的新工艺,微球的理化性质良好。     

复合碳酸钙空腔纳米粒的制备及性能评价

目的 制备甘草次酸/海藻酸钠修饰碳酸钙空腔纳米粒并进行体外评价。方法 以可溶性淀粉为模板剂制备中空球状碳酸钙纳米粒（CaCO3 Nps）;在非均相体系中合成了甘草次酸/海藻酸钠聚合物（GA-ALG）;并以聚合物（GA-ALG）为壳以中空结构的碳酸钙纳米粒为核,合成了壳核结构的GA-ALG-CaCO3 Nps。采用Malvern粒度分析仪测定纳米粒子的粒度分布和Zeta电位,并通过SEM对纳米粒的形态进行表征。应用荧光分光光度计评价载盐酸阿霉素（DOX）纳米粒的载药量、包封率及体外释放特征。结果 纳米粒分布均一,平均粒径为（425.4±31.1）nm,PDI为0.289,Zeta 电位为（-17.0±0.3）mV。药物的载药量为（13.06±0.51）%,包封率为（78.35±3.08）%。;体外释放结果显示,纳米粒具有一定的缓释作用。结论 GA-ALG-CaCO3 Nps作为新型的药物载体,具有良好的pH响应性,并能显著提高载药量,还具有明显的缓释效果,为新型的纳米给药系统的深入研究提供参考。     

美罗培南-海藻酸钙微球的制备与性能研究

目的 针对野战条件下战创伤感染缺乏长效抑菌杀菌药物现状,研制一种高效、安全、易用的新型外用抗感染复合材料.方法 应用天然高分子海藻酸钠、无水氯化钙为基质材料,强效抗生素美罗培南为包被药物,采用静电液滴法及冷冻干燥等制备工艺,制备美罗培南-海藻酸钙微球,并对其包封率、载药量、膨胀性及体外释药性进行检测,采用模拟药敏纸片法对其抑菌效果进行评估.结果 所制备的载药微球包封率为62.27%,载药量为19.40%,膨胀率可达80%;微球的释药模式符合缓释特征,可长效抑菌.结论 静电液滴法制备美罗培南-海藻酸钙微球具有可行性,微球性质稳定,释药模式理想、抑菌效果好.     

Formulation and evaluation of floating drug delivery system of famotidine

A multiple unit oral floating drug delivery system of famotidine was developed to prolong gastric residence time, target stomach mucosa and increase drug bioavailability. Drug and polymer compatibility was studied by subjecting physical mixtures of drug and polymers to differential scanning calorimetry. Cod liver oil entrapped calcium alginate beads containing famotidine, capable of floating in the gastric condition were formulated and evaluated. The gel beads were prepared by emulsion gelation method by employing sodium alginate alone and mixture of sodium alginate and hydrophilic copolymers such as carbopol 934P and hydroxypropylmethylcellulose K15M grade in three different ratios. The effect of selected factors, such as percentage of oil and amount of copolymers on floating properties was investigated. The beads were evaluated for percent drug loading, drug entrapment efficiency, buoyancy and in vitro drug release. The in vitro drug release study of the beads was carried out in simulated gastric media employing a modified Rosette-Rice test apparatus. Wherein, the apparatus was further modified by incorporating a water jacket to the apparatus to circulate hot water to maintain 37±2° for throughout the release study. All the oil entrapped calcium alginate beads floated if a sufficient amount of oil was used. Beads formulated employing sodium alginate alone could not sustain the drug release up to 8 h, whereas beads formulated with mixture of sodium alginate and copolymers demonstrated sustained release of famotidine up to 8 h. The results suggested that cod liver oil entrapped calcium alginate beads were promising as a carrier for intragastric floating drug delivery of famotidine.     

Prolonged injectable formulation of Nafarelin using in situ gel combination delivery system

The principal purpose of the present study was to prepare and characterize a complex drug delivery system consisting of Nafarelin-poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanoparticles (NPs) in combination with sodium alginate/poloxamer 407 in situ gel. Nafarelin-loaded PHBV NPs were prepared via double emulsion solvent evaporation technique. Box–Behnken Response Surface Methodology was utilized to optimize NPs. Mean particle size, polydispersity index (PDI), entrapment efficiency (EE), and drug loading (DL) of the optimized NPs were measured. Incorporation of Nafarelin within NPs was proven by differential scanning calorimetry (DSC). The combination delivery system (CDS) was prepared by adding Nafarelin-loaded PHBV NPs to sodium alginate/poloxamer 407 solution followed by physical mixing. Morphological properties of Nafarelin-loaded PHBV NPs and CDS were evaluated by SEM. Rheological properties were employed to investigate the effects of alginate concentration on sol–gel transition temperature. The release profile of Nafarelin from both PHBV NPs and CDS were individually assessed. The cumulative release percentage from CDS was significantly lower than Nafarelin released from PHBV NPs. Based on the favorable results in this study, the CDS consisting of sodium alginate/poloxamer 407 loaded with PHBV NPs could be a promising candidate for designing a long-lasting formulation of Nafarelin.     

Sodium alginate microspheres of metformin HCl: formulation and in vitro evaluation

Metformin microspheres with sodium alginate alone and in combination with gellan were prepared using an emulsion-cross linking method. The prepared microspheres were evaluated for their physico-chemical characteristics like particle size, morphology using SEM, incorporation efficiency, equilibrium water content (swelling) and in vitro drug release. The effect of various formulation variables like polymer concentration (sodium alginate; and proportion of gellan in microspheres prepared by a combination of sodium alginate and gellan), drug loading, crosslinking agent concentration and cross-linking time on the in vitro dissolution of the prepared microspheres were evaluated. The results showed that both the particle size and the incorporation efficiency were proportional to the polymer concentration. In case of microspheres containing both sodium alginate and gellan, the mean diameter and the incorporation efficiency were higher than the corresponding microspheres containing only alginate, both increasing with an increase in proportion of gellan. The prepared microspheres were found to be discrete and spherical in shape and were successful in sustaining the drug release for 8 hours. Incorporation of gellan caused a significant decrease in drug release. The release followed a biphasic profile, in all cases, characterized by an initial phase of moderate drug release followed by a phase of higher release. Further, the kinetic treatment of the dissolution data revealed the prevalence of matrix diffusion kinetics.     

鞣花酸壳聚糖-海藻酸钠微球的制备工艺

目的:优化鞣花酸壳聚糖-海藻酸钠微球的最佳制备工艺。方法:采用一步法,以壳聚糖-海藻酸钠作为载体材料制备鞣花酸微球,并以微球载药量和包封率为考察指标,通过单因素筛选及正交设计优化出鞣花酸壳聚糖-海藻酸钠微球的制备工艺。用溶出仪在900 ml释放介质(pH 6.86)和120 r·min^-1转速条件下测定释放度。结果:优化工艺为海藻酸钠与药物比为3:1,氯化钙质量分数为2%,海藻酸钠质量分数为2%,壳聚糖质量分数为0.1%,温度为60℃,pH为5,所得鞣花酸平均粒径为(980±100)μm,平均载药量为27.22%,平均包封率为97.73%,48 h释放度为74.22%。结论:本制备工艺稳定,操作简便,重现性好,可用于鞣花酸壳聚糖-海藻酸钠微球的制备。     

Spray-Dried Lactose Composite Particles Containing an Ion Complex of Alginate-Chitosan for Designing a Dry-Coated Tablet Having a Time-Controlled Releasing Function

Purpose. The properties of novel spray-dried lactose compositeparticles suitable for the coating filler of a dry-coated tablet having a longinduction period in drug release were investigated. Methods. To prepare spray-dried composite particles containingalginate-chitosan complex (SD(L/AL-CS)), an aqueous solution of lactoseand sodium alginate and the acetic acid solution of chitosan wereconcomitantly fed into the rotary atomizer of a spray-dryer. Theformation of the alginate-chitosan complex was confirmed by measuring theweight of insoluble portion in the mixture of sodium alginate andchitosan solutions. The dissolution properties of the dry-coated tabletwere measured with the JP specified paddle method. Results. The micromeritic properties of SD(L/AL-CS) were comparedto those of the SD composite particles of lactose-sodium alginate,having a good compacting property. The drug release profiles ofdry-coated tablet with SD(L/AL-CS) contained a long induction periodfollowed by a rapid drug release phase in the artificial intestinal fluid.The induction period for drug release to occur was increased with anincrease in the degree of deacetylation of chitosan and in the amountof chitosan in the formulation. The prolongation of induction periodwas attributed to the formation of an insoluble ion complex betweensodium alginate and chitosan in the composite particles, which couldform a rigid gel structure on the tablet surface. Conclusions. A time-controlled release tablet was designed with thecomposite particles of lactose containing the alginate-chitosan ioncomplex. The induction period of the dry-coated tablet could be prolongedin order to deliver the drug to the colon by controlling the type andamount of chitosan formulated in the composite particles.     

载阿霉素海藻酸钠纳米粒的制备及体外释药行为研究

目的以海藻酸钠(sodium alginate,ALG)为材料,制备载阿霉素海藻酸钠纳米粒(doxorubicin loading nanoparticles,DOX-ALG-NPs),并对其载药、释药特性进行研究。方法采用微乳-离子交联法制备空白海藻酸钠纳米粒(ALG-NPs),以吸附法载药制备阿霉素海藻酸钠纳米粒(DOX-ALG-NPs)。采用效应面法对ALG-NPs的处方进行优化,并考察ALG-NPs悬液浓度、药载比、孵育时间及孵育温度对ALG-NPs载药性能的影响。对DOX-ALG-NPs的基本性质及体外释药行为进行考察。结果成功制备了粒径为(262.0±4.5)nm的ALG-NPs及粒径为(159.8±8.1)nm、包封率及载药量分别为(94.2±0.5)%和(19.05±0.085)%的DOX-ALG-NPs。与原料药DOX相比,DOX-ALG-NPs在生理盐水与PBS(pH=7.4)中均呈现明显的缓释作用,在生理盐水和PBS中2 h与5 h时分别释放药物(38.1±1.5)%与(55.5±1.1)%、(40.0±1.8)%与(48.1±2.5)%,24 h时分别释放(73.1±3.2)%、(60.3±3.4)%。结论所制备的DOX-ALG-NPs形态圆整,粒径小且分布均匀,包封率及载药量较高,具有缓释性能,有望用作抗癌药物传递系统。     

Sodium alginate microspheres of metoprolol tartrate for intranasal systemic delivery: development and evaluation

Bioadhesive sodium alginate microspheres of Metoprolol tartrate (MT) for intranasal systemic delivery were prepared to avoid the first-pass effect, as an alternative therapy to injection, and to obtain improved therapeutic efficacy in the treatment of hypertension and angina pectoris. The microspheres (Ms) were prepared using emulsification--cross-linking method. The formulation variables were drug loading, polymer concentration, cross-linking agent concentration, and cross-linking time. The Ms were evaluated for characteristics, like particle size, incorporation efficiency, swelling ability, in vitro bioadhesion, in vitro drug release, and in vivo pharmacodynamic performance in rabbits against isoprenaline-induced tachycardia. Treatment of in vitro data to different kinetic equations indicated matrix-diffusion controlled drug delivery from sodium alginate Ms. Polymer concentration, cross-linking agent concentration, and cross-linking time influenced the drug release profiles significantly. In vivo studies indicated significantly improved therapeutic efficacy of MT from Ms with sustained and controlled inhibition of isoprenaline-induced tachycardia as compared with oral and nasal administration of drug solution.     

Gastric floating matrix tablets: design and optimization using combination of polymers

The purpose of the present study was to develop an optimized gastric floating drug delivery system (GFDDS) containing domperidone as a model drug. Box-Behnken design was employed in formulating the GFDDS with three polymers: hydroxypropyl methylcellulose K4M (HPMC K4M) (X1), Carbopol 934P (X2) and sodium alginate (X3), as independent variables. Floating lag time (FLT), total floating time (TFT), time required to release 50% of the drug (t50) and diffusion exponent (n) were selected as dependent variables. Seventeen formulations were prepared, dissolution data obtained was fitted to the power law and floating profiles were analyzed. HPMC loading was found to be significant for floating properties. Carbopol loading had a negative effect on floating properties but was found helpful in controlling the release rate of the drug. No significant effect of sodium alginate on floating properties was observed but it was important for gel formation. The quadratic mathematical model developed could be used to predict formulations with desired release and floating properties.