阿莫西林脉冲释药微丸的研制

目的:制备阿莫西林脉冲释药微丸。方法:取空白丸芯分别以含药层、溶胀层(羧甲基淀粉钠)和控释层(乙基纤维素水分散体)顺序依次进行包衣制备阿莫西林脉冲释药微丸。采用紫外法和篮法考察溶胀层(12%、16%、20%)和控释层包衣增重(24%、28%、32%)及不同介质(水、盐酸、pH6.8磷酸盐缓冲液)对药物释放的影响。结果:溶胀层和控释层包衣增重对脉冲控释微丸的释药时滞和释放速率具有显著影响,药物释放情况不受介质pH值的影响;溶胀层和控释层包衣增重分别为16%、28%时制备的微丸时滞时间约为4h,时滞后4h累积释药率达到80%。结论:所制备的阿莫西林脉冲释药微丸具有体外脉冲释放作用。     

Caffeic Acid Phenethyl Ester Loaded Electrospun Nanofibers for Wound Dressing Application

Electrospinning is an advantageous method with a wide usage area, which enables the production of materials consisting of nano-thickness fibers. In this study, caffeic acid phenethyl ester (CAPE) molecule was loaded onto the poly(lactic-co-glycolic acid) (PLGA) nanofibers and obtained nanofibers were physicochemically and biologically investigated for the first time in the literature. The existence of CAPE molecules, loaded on PLGA membranes by dropping and spraying methods, was evaluated by a comparative investigation of Fourier-transform infrared (FTIR) spectra and X-Ray diffraction (XRD) patterns. Fiber morphology of the membranes was investigated by scanning electron microscope (SEM). CAPE release and swelling behaviors of the membranes were studied in vitro. The radical scavenging activity of CAPE-loaded wound dressing materials was determined by using an antioxidant assay. The antimicrobial properties of PLGA and CAPE-loaded PLGA membranes were evaluated against S. aureus, P. aeruginosa and C. albicans strains by the time-kill method. The biocompatibility study of the obtained CAPE-loaded fibers conducted on human fibroblast cell line and wound healing promoting effect of the fibers was investigated in vitro scratch assay.The results show that CAPE-loaded PLGA membranes are highly antimicrobial against all strains used in the experiment. Additionally, the results show that they are biocompatible and have wound healing properties on human fibroblasts.     

Controlled Release of Chitosan and Sericin from the Microspheres-Embedded Wound Dressing for the Prolonged Anti-microbial and Wound Healing Efficacy

One approach in wound dressing development is to incorporate active molecules or drugs in the dressing. In order to reduce the frequency of dressing changes as well as to prolong wound healing efficacy, wound dressings that can sustain the release of the active molecules should be developed. In our previous work, we developed chitosan/sericin (CH/SS) microspheres that released sericin in a controlled rate. However, the difficulty of applying the microspheres that easily diffuse and quickly degrade onto the wound was its limitations. In this study, we aimed to develop wound dressing materials which are easier to apply and to provide extended release of sericin. Different amounts of CH/SS microspheres were embedded into various compositions of polyvinyl alcohol/gelatin (PVA/G) scaffolds and fabricated using freeze-drying and glutaraldehyde crosslinking techniques. The obtained CH/SS microspheres-embedded scaffolds with appropriate design and formulation were introduced as a wound dressing material. Sericin was released from the microspheres and the scaffolds in a sustained manner. Furthermore, an optimized formation of the microspheres-embedded scaffolds (2PVA2G+2CHSS) was shown to possess an effective antimicrobial activity against both gram-positive and gram-negative bacteria. These microspheres-embedded scaffolds were not toxic to L929 mouse fibroblast cells, and they did not irritate the tissue when applied to the wound. Finally, probably by the sustained release of sericin, these microspheres-embedded scaffolds could promote wound healing as well as or slightly better than a clinically used wound dressing (Allevyn®) in a mouse model. The antimicrobial CH/SS microspheres-embedded PVA/G scaffolds with sustained release of sericin would appear to be a promising candidate for wound dressing application.     

Preparation and Characterization of Platelet Lysate (Pl)-Loaded Electrospun Nanofibers for Epidermal Wound Healing

Skin defects are among the most prevalent and serious problems worldwide; it is necessary to provide appropriate coverage in order to reduce possible mortality risk and accelerate wound healing. In this study, we have designed a series of extracellular matrix (ECM)-mimicking nanofibrous scaffolds composed of both natural (gelatin (GEL) and chitosan (CS)) and synthetic (poly(ε-caprolactone) (PCL) and poly (vinyl alcohol) (PVA)) polymers. The 3D constructs (PCL/GEL-PVA/CS) were reinforced with 5% (w/w) of platelet lysate (PL) for promoting cells viability and mobility. The physicochemical characterizations of nanofibers confirmed suitable hydrophilicity, controlled degradability, and water uptake of 250.31 ± 62.74%, and 222.425 ± 86.37% for the PCL/GEL-PVA/CS and PCL/GEL-PVA/CS + PL nanofibers, respectively. The scanning electron microscopy (SEM) images exhibited the mean diameter of the fabricated fibers (PCL/GEL-PVA/CS) in the range of 454 ± 257 nm. The blended samples (PCL/GEL-PVA/CS) were also confirmed to have higher ultimate tensile stress (UTS) (3.71 ± 0.32 MPa). From a biological point of view, the fabricated scaffolds showed appropriate blood compatibility and great potential to avoid bacterial invasion. Altogether, the tailored fabrication of PCL/GEL-PVA/CS nanofibers may be considered a suitable construct for epidermal wound healing.     

Sustained Release of Amoxicillin from Chitosan Tablets

Sustained release systems in the forms of chitosan (CTS) tablet and extrude for releasing amoxicillin were studied. The degradation of amoxicillin in pH 1.2 was determined. The effects of particle sizes of chitosan on the dissolution profiles were investigated. The result showed that chitosan with the particle size less than 75 microm yielded the best controlled release pattern and it was comparable to that was obtained from the hydroxypropylmethylcellulose (HPMC) tablets. Moreover, the tablets containing chitosan with particle size less than 75 microm were able to provide a significantly improved sustained release profile of amoxicillin compared to the release profile of a commercial capsule. All release profiles of amoxicillin from the chitosan tablets could be described by first-order kinetics.     

Plasticized Drug‐Loaded Melt Electrospun Polymer Mats: Characterization,Thermal Degradation,and Release Kinetics

Melt electrospinning (MES) was used to prepare fast dissolving fibrous drug delivery systems in the presence of plasticizers. This new method was found promising in the field of pharmaceutical formulation because it combines the advantages of melt extrusion and solvent‐based electrospinning. Lowering of the process temperature was performed using plasticizers in order to avoid undesired thermal degradation. Carvedilol (CAR), a poorly water‐soluble and thermal‐sensitive model drug, was introduced into an amorphous methacrylate terpolymer matrix, Eudragit® E, suitable for fiber formation. Three plasticizers (triacetin, Tween® 80, and polyethylene glycol 1500) were tested, all of which lowered the process temperature effectively. Scanning electron microscopy, X‐ray diffraction, differential scanning calorimetry, and Raman microspectrometry investigations showed that crystalline CAR turned into an amorphous form during processing and preserved it for longer time. In vitro dissolution studies revealed ultrafast drug dissolution of the fibrous samples. According to the HPLC impurity tests, the reduced stability of CAR under conditions applied without plasticizer could be avoided using plasticizers, whereas storage tests also indicated the importance of optimizing the process parameters during MES. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:1278–1287, 2014     

环丙沙星聚乳酸微球的制备、性状和体外释药性能的研究

目的采用乳化-溶剂蒸发法制备环丙沙星聚乳酸微球,并对其性状进行考察.方法通过正交设计试验筛选其最佳制备工艺, 用电子显微镜观察微球表面形态, 差示扫描热分析确证含药微球的形成, 并对微球的平均粒径、载药量、包封率、体外释药性能进行了研究.结果环丙沙星聚乳酸微球的形态圆整, 且药物确已被包裹在微球中, 微球的平均粒径为280.80±0.15 μm, 粒径在250-390 μm之间的占总数的90%以上. 包封率为68.5%±0.58, 载药量为34.1%±0.51,环丙沙星微球的体外释药情况为53.2小时的累积释药量为84.0%,T1/2为31.9 h, Higuchi方程为Q=-0.004 3 0.003 9 t1/2,r=0.994 1.结论本研究获得了较满意的制备环丙沙星聚乳酸微球的工艺, 且微球的体外释药性能具有明显的缓释效果.     

褪黑素缓释片的制备及其药代动力学研究

目的　研制褪黑素HPMC骨架缓释片。并且研究缓释片的药物动力学及生物利用度。方法　以HPMC为骨架制备褪黑素缓释片。考察褪黑素的颗粒大小 ,片剂中HPMC的种类及含量 ,片剂大小 ,填充物的种类及数量 ,压片力等影响药物释放度的因素。采用HPLC荧光检测器测定家犬静脉注射及口服褪黑素后的血药浓度。结果　褪黑素静脉注射后体内血药浓度符合双隔室模型。静注两种剂量后AUC与剂量成正比 ,生物半衰期分别为 6 7 7分和 84 6分 (P >0 0 5 )。褪黑素缓释片相对于常释胶囊的生物利用度为 83 8%。缓释片及常释胶囊的绝对生物利用度分别为 3 75 %及 4 4 9%。结论　褪黑素缓释片具有良好的缓释特性。褪黑素缓释片及常释胶囊的绝对生物利用度都较低 ,缓释片的生物利用度低于常释胶囊但体内平均滞留时间显著长于常释胶囊。缓释片的体外释放与体内吸收速度有良好的相关性。     

阿莫西林胶囊的制备及溶出度研究

目的：提高阿莫西林的溶出度。方法：阿莫西林胶囊处方组成为每柱含阿莫西林0．25g,硬脂酸镁0．0075g,羧甲淀粉钠0．01g。结果：阿莫西林原粉溶出80％所需时间为65．37min,阿莫西林胶囊为20．56min。结论：本制备方法能明显提高其溶出度。     

紫杉醇MPEG-PCL纳米粒的制备、表征及其体外释药行为研究

目的 以聚乙二醇单甲醚-聚己内酯(MPEG-PCL)为载体制备紫杉醇MPEG-PCL纳米粒并对其体外释放行为进行考察。方法 采用开环聚合法合成MPEG-PCL共聚物,采用核磁共振波谱仪(¹H-NMR)、傅里叶红外光谱仪(FTIR)对其进行表征;通过共沉淀法制备了紫杉醇MPEG-PCL纳米粒,并测定了粒径分布、Zeta电位、结构特征、包封率以及载药量;同时以磷酸盐缓冲溶液(pH=7.4)为释放介质考察其体外释放行为。结果 成功合成了相对分子质量为4 875的MPEG-PCL共聚物。透射电镜结果显示紫杉醇MPEG-PCL纳米粒具有规则的球形结构,纳米粒的平均粒径为(102.3±3.5)nm,PDI=0.102,药物包封率和载药量分别为(95.6±3.2)%和(8.5±0.4)%。体外释放结果显示紫杉醇可以缓慢的从MPEG-PCL纳米粒中释放出来。结论 MPEG-PCL共聚物是紫杉醇的良好载体,所制备的纳米粒具有包封率和载药量高、药物释放缓慢的特点。     

左氧氟沙星/PLGA亚微粒的制备、表征和体外释药考察

目的:制备左氧氟沙星/PLGA亚微粒,并进行相关表征和体外释放行为考察.方法:采用纳米共沉淀法制备左氧氟沙星/PLGA亚微粒,采用激光粒度分析仪以及扫描电镜分别进行亚微粒粒度测定和形貌分析.同时采用紫外-可见分光光度法(UV)测定其载药量与体外药物释放行为.结果:经过激光粒度分析仪测定,所制备的左氧氟沙星/PLGA亚微粒粒径为197 ～230 nm,Zeta电位为-24 mv.扫描电镜观察亚微粒呈圆形/椭圆形,分布均匀.UV法测定亚微粒的载药量为6.25％～9.38％,包封产率为12.45％ ～46.59％.体外释放结果显示相比于商品化左氧氟沙星滴眼液,所制备的左氧氟沙星/PLGA亚微粒具有良好的缓释效果.结论:通过纳米共沉淀法成功制备粒径均一,高载药量的左氧氟沙星PLGA亚微粒,同时能实现药物的缓慢释放,减少给药次数的目的.     

大黄素固体分散体制备、表征与释药机制研究

目的 制备大黄素固体分散体,提高其体外溶出度并探究其释药机制。方法 采用分子对接技术,辅助筛选聚合物载体。以大黄素为原料药,Kollidon^® VA64为聚合物载体,采用热熔挤出工艺制备大黄素固体分散体。通过溶出仪测定其体外溶出,利用SEM、DCS和PXRD对原料药和固体分散体的表面形态和晶型进行表征,最后采用FTIR、NMR和分子动力学模拟对固体分散体的释药机制进行探究。结果 相较于大黄素原料药,大黄素固体分散体在4种介质中的溶出被明显改善,大黄素由结晶态转化为无定形态,药物与聚合物载体间形成了氢键。结论 固体分散体中药物晶型的转变和氢键的产生是改善药物体外溶出的主要因素。     

Delivery of Therapeutics from Layer-by-Layer Electrospun Nanofiber Matrix for Wound Healing: An Update

Increasing incidences of chronic wounds urge the development of effective therapeutic wound treatment. As the conventional wound dressings are found not to comply with all the requirements of an ideal wound dressing, the development of alternative and effective dressings is demanded. Over the past few years, electrospun nanofiber has been recognized as a better system for wound dressing and hence has been studied extensively. Most of the electrospun nanofiber dressings were fabricated as single-layer structure mats. However, this design is less favorable for the effective healing of wounds mainly due to its burst release effect. To address this problem and to simulate the organized skin layer's structure and function, a multilayer structure of wound dressing had been proposed. This design enables a sustained release of the therapeutic agent(s), and more resembles the natural skin extracellular matrix. Multilayer structure is also referred to layer-by-layer (LbL), which has been established as an innovative method of drug incorporation and delivery, combines a high surface area of electrospun nanofibers with the multilayer structure mat. This review focuses on LbL multilayer electrospun nanofiber as a superior strategy in designing an optimal wound dressing.     

紫外分光光度法测定创伤敷料中红霉素的含量

目的建立分光光度法测定敷料中的红霉素含量.方法红霉素与氢氧化钠反应生成在234 nm处有最大吸收峰的不饱和酮,根据不饱和酮的紫外吸收峰值来测定敷料中的红霉素的含量,通过反应动力学的考察,重新确定氢氧化钠的用量、反应时间,并作标准曲线和回收率.结果样品浓度在20～80μg·ml-1,氢氧化钠浓度为0.25 mol·L-1,反应温度为60℃,反应时间30min时,反应结果稳定,能准确测定敷料中的红霉素含量.标准曲线方程为A=8.895×10-3 C 0.03214,r=0.9999;平均回收率为100.3%,RSD=0.76%(n=9).结论本法测定准确,重现性好,操作简便.     

Preparation,Characterization, and Pharmaceutical Application of Linear Dextrins. III. Drug Release from Fatty Suppository Bases Containing Amylodextrin

Drug release from fatty suppository bases containing a solid dispersion of diazepam with amylodextrin or a complex of prednisolone with amylodextrin was analyzed in a flow-through model. Being present as a suspension in the fatty base, particles of complex or solid dispersion are transported to the lipid–water interface by sedimentation. After entering the aqueous phase they partially dissolve. The suppositories showed increased drug release compared with the corresponding suppositories containing drug only. Because of the partial solubility of amylodextrin, drug release was lower than the release from drug–cyclodextrin complexes. Use of the soluble fraction of amylodextrin for both the solid dispersion and the complex further enhanced drug release, but it was still below that of drug–cyclodextrin complexes.     

Formulation,Characterization, and In Vitro Release of Glyburide from Proliposomal Beads

The objective of our study was to formulate and evaluate proliposomes in the form of enteric-coated beads using glyburide as a model drug. The beads were enteric coated with Eudragit L-100 by a fluidized bed coating process using triethyl citrate as plasticizer. Content uniformity of glyburide was estimated using HPLC analysis of beads dissolved in methanol. These proliposomal beads formed liposomes on disintegration in phosphate buffered saline (pH 7.4), which was confirmed by transmission electron microscopy. The dissolution study of enteric-coated beads exhibited enhanced dissolution compared with pure drug and a marketed product. Liposomes can be successfully prepared for oral administration in the form of enteric-coated beads that may offer a stable system to produce liposomes for oral administration.     

厚朴酚聚乙二醇-聚L-乳酸电纺纤维的制备及酶降解药物释放

以聚乙二醇-聚L-乳酸为载体材料,用高压静电纺丝法制得包载厚朴酚的纤维毡.扫描电镜和Photoshop 5.0软件测定结果表明得到了表面光滑、直径较均一的纤维;广角X-射线衍射结果表明载药纤维表面无药物结晶.采用HPLC法测定了载药纤维毡中厚朴酚在含或不含蛋白酶K的磷酸盐缓冲液中的累积释放率.结果表明,当介质中加入蛋白酶K(含量为2.5 μg/ml)后,厚朴酚的释放速率即明显加快.酶浓度由2.5 μg/ml升至10 μg/ml时,厚朴酚释放速率继续增加,但增幅较小.介质中无蛋白酶K存在时,将释放曲线分段后用Higuchi方程拟合效果较好;有蛋白酶K存在时,药物释放曲线在平台期前呈现一级释放动力学形式.     

复方阿莫西林胶囊的制备与质量控制

目的 制备复方阿莫西林胶囊,并探讨其质量控制方法 . 方法 以湿法制粒制备复方胶囊,采用高效液相色谱法测定复方胶囊的含量与溶出度. 结果阿莫西林与氨溴索回归方程的线性范围分别为80～320 μg.mL^-1和4.8～19.2 μg.mL^-1,加样回收率分别为96.72%和104.17%,RSD分别为1.84%和0.57%. 3批样品的含量均>90%,45 min溶出度>80%. 结论 复方阿莫西林胶囊的含量与溶出度均符合2010年版《中华人民共和国药典》要求,该检测方法 准确、简便,分离效果好,可用于该复方胶囊的质量控制.     

复方阿莫西林干混悬剂的制备与含量测定

目的:研制复方阿莫西林干混悬剂,并建立HPLC法对其含量进行测定。方法:采用单因素方法考察不同辅料对复方阿莫西林干混悬剂沉降体积比及再分散性的影响,并通过正交试验设计,优化处方工艺。采用HPLC法测定阿莫西林和盐酸氨溴索的含量。色谱柱:Inertsil ODS-2柱（150 mm×4.6 mm,5μm）;流动相:甲醇-0.01 mol·L^-1醋酸铵溶液（52:48）,流速:1.0 ml·min^-1,柱温:25℃,检测波长:247 nm。结果:最佳工艺为:以黄原胶（用量为12%）和羧甲基纤维素钠（用量为4%）共同作为助悬剂,微晶纤维素（用量为15%）为崩解剂,12%的聚维酮（50%乙醇溶液）为黏合剂。阿莫西林和盐酸氨溴索线性范围分别为80～320μg·ml^-1和9.6～24μg·ml^-1,加样回收率分别为96.14%和96.86%,RSD分别为1.47%和0.92%。结论:筛选优化的制备工艺稳定可控,重复性好;该检测方法简便,准确,专属性强,可用于复方阿莫西林干混悬剂的质量控制。