影响聚酯微球中药物释放的因素

聚酯材料因其原料易得、容易加工、生物相容性好、具有可生物降解性等优点,已经成为当今药物载体材料中的一大研究热点。现综合国内外的有关报道对可生物降解聚酯材料作为药物载体制备微球制剂的研究进展进行了综述。针对目前限制聚酯材料微球制剂临床应用存在的问题,从聚合物、药物、制备工艺、附加剂、辐射灭菌5个方面对影响聚乳酸(PLA)和聚乳酸乙醇酸共聚物(PLGA)缓释微球中药物释放的因素进行了重点介绍,为研究聚酯微球中药物的释放提供思路。     

微球给药系统研究进展

微球(microsphere)是指药物溶解或者分散在高分子材料基质中形成的微小球状实体,常见粒径在1—40μm之间,属于基质型骨架微粒。微球用于药物载体的研究始于20世纪70年代中期,发展十分迅速。药物制成微球后,因其对特定器官和组织的靶向性及微粒中药物释放的缓释性,已经成为近年来缓控释剂型研究的热点。微球根据材料可分为生物降解型、非生物降解型;根据临床用途可分为非靶向制剂和靶向制剂^[1]。     

微球化技术在中药制剂中的研究进展

微球制剂是近年来利用微球化技术发展的药物新剂型,微球化技术指利用适宜的高分子聚合物材料作为载体,将固体或液体药物包裹而形成微粒分散系统的技术,形成的微粒属于基质型骨架微粒,大小1～300 μm[1].     

微球给药系统及其质量评价

目的 为开展药物新剂型研究提供参考.方法 查阅相关专业文献,对微球给药系统的制备方法及质量评价进行综述.结果 微球给药系统的制备方法有溶剂挥发法、喷雾干燥法、乳化交联法.微球给药系统的质量评价包括形态及粒径分布、载药量及包封率、微球的释放速率、稳定性等.结论 微球给药系统作为一种新剂型,近年来受到广泛关注,具有广阔的发展前景.     

环糊精及其衍生物在微球中的应用研究进展

目的介绍环糊精及其衍生物在微球给药系统中的应用。方法经文献检索,以其中的37篇为依据对环糊精及其衍生物作为微球的载体材料、致孔剂、表面改性剂、分散稳定剂以及改善微球中药物的性质等方面的研究进行阐述。结果环糊精及其衍生物是制备或改进微球性质的有效辅料。结论环糊精及其衍生物在药物新剂型研制方面具有良好的应用前景。     

糖皮质激素缓释微球的制备与性质

目的:制备糖皮质激素微球,探讨工艺条件对成球的影响,并测定微球粒径及体外药物溶出度、药物释放时间等性质.方法:以胶原、壳聚糖、明胶等3种天然生物高分子作材料,采用复乳-交联法制备糖皮质激素微球,用显微镜和扫描电镜观察微球形态和粒径分布.模拟探讨糖皮质激素微球的药物释放行为,用反相高效液相色谱法(HPLC)测定微球释放出的药物浓度.结果:按本工艺制作的微球,有90.8%粒径在20～100μm范围内,平均粒径66.6μm,大小适中,体外模拟实验表明,经过7d,药物溶出率约为51.7%～67.8%,与释放介质的pH值相关,具有较好的缓释性能.结论:该缓释体系有望作为新型的糖皮质激素药物新剂型.     

纳米技术与药物新剂型

目的:介绍纳米技术与药物新剂型的研究与发展的关系。方法:将现有已报道的药物新剂型对照纳米技术制备制剂的要求,以肯定现有已达或未达纳米粒度的药物新剂型,找出其进一步提高和发展的方向。结 果:明确了部分药物新剂型如溶液型固体分散体、环糊精包合物、微乳、小单层脂质体、毫微囊、毫微球等,实际上已达到纳米粒度药物的要求;而其它类型的固体分散体、微囊剂和微球剂等,尚属微米粒度的药物新剂型。结论:纳米技术与药物新剂型的关系甚为密切,为今后应用纳米技术研究和发展药物新剂型奠定了基础,并显示其强有力的促进作用和保证作用。     

药物缓控释制剂的研究概况

缓控释制剂是指在水中或某些特殊介质中缓慢释放药物的制剂,可适用于多种给药途径,制作成多种药用剂型。缓控释制剂作为一种特殊释药系统一直在药剂专业范围内被广泛关注。本文就缓控释制剂的载体材料及剂型进行概述。     

几种抗菌药物新剂型药代动力学研究概况

目的 :根据文献资料综述抗菌药物新剂型在细胞、组织的药物动力学特点。方法 :按抗菌药物的脂质体、纳米球、微球、微囊分别介绍。结果 :抗菌药物脂质体、纳米球、微球等可提高感染细胞或组织的药物浓度 ,同时具有缓释特性 ,延长有效药物浓度维持时间。结论 :新型给药系统具有靶向性 ,增强抗菌活性 ,降低毒性 ;一些抗菌药物适合制成脂质体、纳米球等新剂型     

我国药物新剂型研究进展

随着药剂学发展突飞猛进,对药物新剂型和新技术的研究与应用也日益广泛、深入。通过查阅2012年我国学者在国内外期刊上发表的相关论文,分类概述我国在纳米制剂、微球、亚微乳、复合物、纳米晶体、立方液晶和碳纳米管等药物新剂型方面的研究进展。     

An easy producible new oral hydrocolloid drug delivery system with a late burst in the release profile

One of the main drawbacks of hydrocolloid matrices as oral controlled drug delivery systems is the often observed decreasing rate of drug release at the end of the release process. This study describes a new pH-controlled hydrocolloid drug delivery system consisting of a neutral cellulose ether as basis polymer and enteric coating materials as additives. The new dosage form is able to accelerate the drug release at a predetermined pH. In a typical example, methylhydroxy ethylcellulose, MHEC 10000 B, was used as the basis polymer and hydroxypropyl methylcellulose acetate succinate, HPMCAS HF, as release modifier. The new delivery system is characterized by its homogeneous structure and easy production by direct compression of the components. The acceleration is well reproducible. Furthermore the new formulation shows high stability against hydrodynamic stress and tolerates ionic strengths up to 0.25 without any significant changes in the release profile. As mechanism of the final burst at pH values >5.7, enforced erosion of the gel layer surrounding the tablet core, could be identified.     

Formulation and in vitro evaluation of rifampicin loaded porous microspheres

Rifampicin (RIF) is a major component in fixed dose combination therapy for the treatment of tuberculosis. RIF has low solubility and high permeability with high dose and hence it is classified as class II drug in Biopharmaceutical Classification System (BCS). RIF has poor and variable bioavailability because of its poor solubility, acid decomposition and, drug and food interaction. The present investigation was aimed to develop RIF loaded porous microspheres as a controlled release dosage form. Eudragit based porous microspheres of RIF were prepared by emulsion solvent diffusion method. Prepared porous microspheres were evaluated for its entrapment efficacy, morphology, thermal behavior, crystalline nature, in-vitro drug release and stability in simulated gastric fluid. The entrapment efficacy of drug loaded microspheres was found to be in the range of 19.04a74.57%. Surface morphology revealed the porous and spherical structure of microspheres. Differential scanning calorimetric studies confirmed that formulation process altered the crystalline nature of RIF. In vitro drug release studies indicated that drug to polymer ratio of 2:1 showed more than 85% drug release over the period of 3 h. Stability studies in simulated gastric fluid (SGF) indicated that low relative decomposition of 18.5% was achieved with high drug to low polymer ratio of 1:4. The results obtained from the present investigation concluded that RIF loaded porous microspheres are suitable for developing oral controlled release dosage form of RIF that can prevent acid decomposition and provide better biopharmaceutical properties. Further more the microspheres can be evaluated for preventing the interaction with isoniazid, other drugs and foodstuffs.     

Preparation and statistical optimization of alginate based stomach specific floating microcapsules of simvastatin

The present study involves preparation and characterization of floating microcapsules with simvastatin as model drug for prolongation of gastric residence time. The main objective is to improve solubility of simvastatin beta-CD complex (1:2) by co-precipitation method and then to deliver the same in sustained release dosage form. Sustained-release simvastatin microcapsules were prepared by the ionic gelation technique, using carbopol 941 as swellable floating polymer. A 3(3) full factorial design was used to study the effect of polymer concentration, drug complex and sodium alginate by plotting main effect plot and 3D surface plots. The formed microcapsules were subjected to various evaluation tests such as drug encapsulation efficiency, in vitro drug release and surface morphology by scanning electron microscopy. Powdered X-ray diffractometry and FTIR were used to investigate the complexation of simvastatin in the microcapsules. As the carbopol 941 is self swellable polymer, immediate floating was observed. The in vitro release studies and floating behavior were performed in HCI buffer of pH 1.2. The release profile and dissolution kinetic showed that drug release from the microcapsules follows zero order kinetics. It was concluded from the present investigation that porous carbopol 941 microcapsules are promising sustained release system as well as stomach specific carriers for delivery of simvastatin.     

尼莫地平由溶胀性亲水性骨架中释放的动力学

本研究选用尼莫地平PVP－K30固体分散体为原料,以羟丙基甲基纤维素（HPMC）为缓释材料,进行了尼莫地平缓释片剂处方的设计,考查其体外释药动力学,并对几种辅及及不同的制备方法对片剂释药情况的影响进行了研究。体外溶出度实验结果表明,在本实验范围内,尼莫地平由HPMC亲水性凝胶骨架片中的溶出过程更符合零级动力学。微晶纤维素的加入可使片剂释药速度加快,低粘度的羟乙基纤维素可使药物的溶出速率常数增加。将HPMC制成40目颗粒后,再行压片,可使药物溶出度减慢。本研究筛选出的缓释片剂,可在12小时内平稳释药。     

Physical ageing of amorphous polymeric excipients III. The possible consequences of ageing

Polymeric excipients are widely used in pharmaceutical technology, and most of them are amorphous or partly amorphous. A well-known property of such materials is that they undergo physical ageing, which is accompanied by volume and enthalpy relaxation and thus might result in severe structural changes in the polymer. This latter phenomenon can influence the properties of excipients and dosage forms, such as processability, mechanical strength and drug release. These alterations are of great significance in the case of solid dosage forms, as physical ageing occurs in the solid state of the polymer. Considering conventional tablets, the structural changes of fillers or binders along with storage can influence the above mentioned properties, while in the case of modified release tablets, matrix-forming and film-forming agents are to be taken into account, as well. In addition to this, by the examination of films, the presence of plasticizers is of great importance, as these materials can facilitate physical ageing via increasing the molecular mobility of the polymer. In the case of certain therapeutic systems (e.g. intrauterine devices), where the base of the dosage form is polymeric, significant changes are to be noted considering the drug release and physiological tolerability of the system.     

Calculation of the blood level of a drug taken orally with a diffusion controlled dosage form

Oral dosage forms with controlled release are generally investigated either by in vitro or in vivo tests and the problem of correlating these results appears. A numerical model is built, taking into account the characteristics of drug release out of the dosage form along the gastrointestinal tract, the stages of absorption in the blood compartment and of elimination. The dosage form is obtained by dispersing theophylline as a drug in Eudragit RS playing the role of a polymer matrix. The process of drug release is controlled by diffusion, with a constant diffusivity. The following results are obtained: the kinetics of release of the drug out of the dosage form, the kinetics of the drug in the blood compartment, and the kinetics of drug elimination.     

聚乳酸-乙醇酸共聚物降解行为对缓控释制剂药物释放行为影响的研究进展

在以聚乳酸–乙醇酸共聚物（PLGA）为辅料的药物缓控释制剂中,药物的释放行为主要取决于PLGA聚合物的降解行为。PLGA的降解行为受骨架结构、环境因素和剂型因素等影响。对PLGA的降解机制进行剖析,并综述影响PLGA降解行为的相关因素,包括PLGA的单体聚乳酸与聚乙醇酸的比例、相对分子质量、pH值、结晶度、温度、药物的类型和基质包封药物后的剂型等,同时论述了其对缓控释制剂药物释放行为的影响。     

Percolative Transport and Cluster Diffusion Near and Below the Percolation Threshold of a Porous Polymeric Matrix

Purpose The purpose of this research was to develop a quantitative mass transport model to describe the release of a drug from a porous inert matrix dosage form near and below the percolation threshold for the system.Methods Cumulative release profiles were generated for a series of tablets composed of a binary mixture of varying amounts of non-conducting (poly(vinyl stearate)) and conducting (benzoic acid) components. The porous microstructure was analyzed using re-constructed three-dimensional images of leached microtomed tablet sections. Poly(vinyl stearate) was characterized for transport properties, molecular weight and thermal properties.Results Based on percolation theory, the binary matrix was determined to have a percolation threshold of 0.09 ± 0.02. Transport, which could not be explained by “classical” percolation theory or surface diffusion alone, was observed below the percolation threshold for the system.Conclusions A model describing transport near and below the percolation threshold in matrices composed of two phases, polymer and drug, was developed. The percolation model developed accounts for diffusion within the porous structure and through the inert, insoluble polymeric amorphous regions of the matrix. The low percolation threshold and subsequently high coordination was concluded to be due to the biphasic classical porous and nonclassical polymeric diffusional transport mechanisms associated with the system studied.     

Preparation and control-release kinetics of isosorbide dinitrate microspheres

Microcapsules for sustained release of poorly soluble isosorbide dinitrate (ISDN) were prepared based on ethylcellulose (EC) and/or blended with appropriate amounts of relatively hydrophilic hydroxypropyl cellulose (HPC) as matrix materials using the oil-in-oil emulsion evaporation method. The microspheres studied had three-mode sizes (100-150, 250-300 and 400-450 microm) and four polymer compositions (1, 0.833, 0.67 and 0.5 weight fraction EC). The microspheres were observed to contain essentially no drug crystalline domain and were of a porous morphology. The cumulative amounts of ISDN releasing from the microspheres as functions of mode fractions size and polymer compositions were measured in vitro. It was observed that the microspheres' size influenced the release behaviour of drug more obviously than the polymer composition. The smaller size and the higher hydrophilic HPC content show the faster release rate of drug and the smaller amount of drug residue. The kinetics of drug release depends on the size and polymer composition. The microspheres with 100-150 microm, of all polymer compositions, present one-stage diffusion kinetic with a lag period for drug release. On the other hand, the microspheres with the other two sizes exhibit two-stage diffusion kinetic with a lag period. According to the kinetic model, the microspheres obtained are surmised to have a core-shell like drug concentration distribution and/or a core-shell morphology.