壳聚糖作为药物缓释载体的研究进展

壳聚糖作为药物缓释载体在减少给药次数,降低药物毒副作用,提高药物疗效等方面具有重要作用。本文综述了壳聚糖作为药物缓释载体的研究进展,主要包括壳聚糖纳米粒子、微球、片、膜和凝胶等的制备和缓释特性,并对其发展趋势进行了展望。     

载银缓释型抗菌敷料

近10年来,载银缓释型抗菌敷料因其优良特性,在医药、卫生等领域引起科学家们的广泛关注。本文综述了银的抗菌机理和载银缓释型抗菌敷料的缓释机制;重点介绍了目前在国际市场上销售的代表性载银缓释型抗菌敷料的性能,并从不同的载体材料角度(如生物高分子、合成高分子、生物和合成高分子共用、有机硅材料)总结了新型载银抗菌敷料的研究进展;最后,讨论了载银抗菌医用敷料在研究和应用中需要解决的问题。     

可生物降解的药物缓释膜片研究进展

利用生物降解高分子材料物理包埋或化学结合需要缓释的药物制成植入膜片,药物从聚合物的孔道中扩散出来,以一定的速率释放,从而达到局部缓释、控释的目的。本文从聚合物材料、制备方法和释放机理等方面综述了近年来国内外生物降解药物缓释膜片的进展情况。     

聚[1,3-双(对羧基苯氧基)丙烷-癸二酸](20:80)-替莫唑胺长效缓释微球的制备及药物缓释性能的研究

合成了聚[1,3-双(对羧基苯氧基)丙烷-癸二酸](20:80)(CPP-SA),并利用喷雾干燥法制备了替莫唑胺Temozolomide(TMZ)-(CPP-SA)缓释微球。通过对TMZ的不同包合方法的研究,确定了喷雾干燥法作为制备此类微球的最佳方法,获得了良好的药物缓释曲线。结果表明,微球对药物释放曲线平稳,释放时间长,能超过800h。为抗肿瘤药物TMZ的体内植入提供了有意义的理论依据。     

在药物缓释体系中应用的可生物降解材料

对目前应用于药物缓释体系中的可生物降解材料的合成及应用作了广泛而深入的总结与评述,并就其发展趋势作了预测。参考文献２０篇。     

聚氨酯生物吸收材料及其作为缓释药物载体的研究

合成了一系列新的紫外光固化生物吸收性聚氨酯水凝胶网络，测定了材料的含水率及水解性能，并以之为载体，研究了对异烟肼的药物缓释性能。结果表明，该水凝胶的含水率及降解速率与其结构有关，该水凝胶对异烟肼具有缓释作用，释放行为受扩散控制并符合Ｈｉｇｕｃｈｉ方程，表观扩散系数与水凝胶的含水率有关。     

聚蔗糖微球缓释载体的研制

药物输送系统(drug delivery system,DDS)主要包括药物和载体两部分,微球(microspheres)是以适宜的高分子材料制成的一种应用较为广泛的新型药物载体。本文研究了聚蔗糖微球的制备方法以及作为药物缓释载体的可行性。以Span-80为表面活性剂,环氧氯丙烷为交联剂,Ficoll-400水溶液为水相(W),氯苯为油相(O),采用反相悬浮聚合法制备了一系列粒径<100μm、圆球率高的聚蔗糖微球。以牛血清蛋白(BSA)为模型药物,研究其作为药物载体的缓释性能。释放实验表明其最大释放率为95%,适当提高其交联程度有利于BSA的缓慢释放。     

电场纺丝法制备药物缓释乙基纤维素纤维的研究

通过把四环素均匀分散在乙基纤维素溶液里,利用电场纺丝法制备了含有四环素的乙基纤维素超细纤维,并运用紫外-可见光分光度计测定了含四环素的乙基纤维素纤维在水中的释放曲线.发现用电场纺丝法制备的含四环素的纤维有良好的药物缓释作用,可以有效避免血液中药物浓度的“峰谷”现象的出现.纤维的直径以及药物在纤维中的浓度都会对四环素的释放效果产生影响,平均直径大的纤维的四环素的释放曲线增长的更为平稳,四环素含量高的纤维的释放曲线浓度高.     

萘普生在新型缓释系统中的释药

亲水凝胶;萘普生;二醋酸纤维素;致孔剂;新型药物缓释系统     

羟丙基甲基纤维素接枝聚己内酯二醇的合成、表征及性能

采用羟丙基甲基纤维素(HPMC)和聚己内酯二醇(PCL)为原料,以4,4'-二苯基甲烷二异氰酸酯(MDI)为接枝桥梁,利用酰胺化反应将PCL接枝到HPMC分子上,成功合成了改性接棱聚合物羟丙基甲基纤维素接枝聚己内酯(HPMC-g-PCL).利用红外光谱(IR)表征了产物结构,探讨了MDI在整个过程的桥联作用,利用热重分析(TGA)和示差扫描量热分析(DSC)对合成产物的热性能进行了表征,结果表明HPMC经PCL接枝改性后,失重率降低,热稳定性得到增强.     

Preparation of hydroxypropylmethyl cellulose-based porous matrix for gastroretentive delivery of gabapentin using the freeze-drying method

The aims of the present study were to prepare hydroxypropylmethyl cellulose (HPMC)-based porous matrix tablets for gastroretentive drug delivery and to characterize their physicochemical properties. Gabapentin (GBP) was used as a model drug. Paste containing GBP, HPMC and water was molded and freeze-dried to prepare freeze-dried gastroretentive matrix tablet (FD-GRT). In vitro drug release and erosion studies were also performed. Although FD-GRT exhibited porous structure, they had good tablet strength and friability. Density of FD-GRT ranged from 0.402 to 0.509 g/cm³ and thus they could float on the medium surface without any lag time. FD-GRT was remained floated until the entire matrix erosion or end of drug release during in vitro release test. Release behavior of GBP could be modulated by the amount and the viscosity grade of HPMC. However, large amount and high viscosity of HPMC caused trouble in molding prior to freeze-drying. Addition of ethylcellulose could retard the release rate of GBP, with relatively low increase in viscosity of paste. Since pores generated by freeze drying imparted buoyancy for gastric retention to FD-GRT, additional materials for buoyancy was not necessary and FD-GRT had no lag time for buoyancy due to low density. Therefore it could be a promising tool for gastroretentive drug delivery.     

Design and in vitro evaluation of zidovudine oral controlled release tablets prepared using hydroxypropyl methylcellulose

Oral controlled release matrix tablets of zidovudine were prepared using different proportions and different viscosity grades of hydroxypropyl methylcellulose. The effect of various formulation factors like polymer proportion, polymer viscosity and compression force on the in vitro release of drug were studied. In vitro release studies were carried out using United States Pharmacopeia (USP) type 1 apparatus (basket method) in 900 ml of pH 6.8 phosphate buffer at 100 rpm. The release kinetics were analyzed using Zero-order model equation, Higuchi's square-root equation and Ritger-Peppas' empirical equation. Compatibility of drug with various formulations excipients used was studied. In vitro release studies revealed that the release rate decreased with increase in polymer proportion and viscosity grade. Increase in compression force was found to decrease the rate of drug release. Matrix tablets containing 10% hydroxypropyl methylcellulose (HPMC) 4000 cps were found to show a good initial drug release of 21% in the first hour and extended the release upto 16 h. Matrix tablets containing 20% HPMC 4000 cps and 10% HPMC 15000 cps showed a first hour release of 18% and extended the release upto 20 h. Mathematical analysis of the release kinetics indicated that the nature of drug release from the matrix tablets followed non-Fickian or anomalous release. No incompatibility was observed between the drug and excipients used in the formulation of matrix tablets. The developed controlled release matrix tablets of zidovudine, with good initial release (17-25% in first hour) and which extend the release upto 16-20 h, can overcome the disadvantages of conventional tablets of zidovudine.     

Study of the critical points in lobenzarit disodium hydrophilic matrices for controlled drug delivery

Percolation theory is a multidisciplinary theory that studies chaotic systems. It has been applied in the pharmaceutical field since 1987. The application of this theory to study the release and hydration rate of hydrophilic matrices allowed for first time to explain the changes in release and hydration kinetic of swellable matrices type controlled delivery systems. The objective of the present paper is to estimate the percolation threshold of HPMC K4M in matrices of lobenzarit disodium and to apply the obtained result to the design of hydrophilic matrices for the controlled delivery of this drug. The materials used to prepare the tablets were Lobenzarit disodium (LBD) and HPMC of viscosity grade K4M. The drug mean particle size was 42+/-0.61 mum and the polymer was sieved and 150-200 microm granulometric fraction was selected. The formulations studied were prepared with different excipient contents in the range of 10-80% w/w. Dissolution studies were carried out using the paddle method and the water uptake measurements were performed using a modified Enslin apparatus. In order to estimate the percolation threshold, the behaviour of the kinetic parameters with respect to the volumetric fraction of each component at time zero, was studied. According to percolation theory, the critical points observed in dissolution and water uptake studies are attributed to the existence of an excipient percolation threshold. This threshold was situated between (18.58 to 24.33% v/v of HPMC). Therefore, the LBD-HPMC K4M matrices with a relative HPMC particle size of should be formulated with an excipient content above 24.33% v/v of HPMC, to obtain a control of the drug release from these systems.     

Anti-tack action of polyvinylpyrrolidone on hydroxypropylmethylcellulose solution

The anti-tack action of polyvinylpyrrolidone (PVP) on hydroxypropylmethylcellulose (HPMC) solution was elucidated using a probe test method. The influence of PVP of varying molecular weights at various PVP concentrations and solution temperatures on the tackiness of HPMC solution was studied. The viscosity, surface tension, cloud point and solution spectroscopy of HPMC solutions and glass transition temperature of HPMC films, with and without PVP, were investigated. The tackiness of HPMC solutions in response to the addition of PVP, at different concentrations of HPMC and using HPMC with varying contents of hydroxypropyl/methoxyl substitution, was also evaluated. PVP is a commonly used binder and adhesive. However, it reduced the tack of the HPMC solution when used at low concentrations, without affecting the state of hydration of HPMC. Lower molecular weight PVP was more effective as an anti-tack agent owing to suitable hydrodynamic size to intersperse among the HPMC chains. The degree of reduction in tack values was more pronounced for HPMC that showed a greater extent of interaction between polymer chains such as when high concentration of HPMC or low solution temperature was employed. This indicated that the tack reduction property of PVP relied on its ability to interact with the HPMC chains. The profile of reduction in tack values was affected by the contents of HPMC substitution and was a result of net reduction in the extent of hydrogen bonding between HPMC chains. It was significantly correlated to the changes of viscosity and surface tension of the HPMC solutions but not to the glass transition temperatures of the polymers prepared as solid films. The results suggested that the anti-tack action of PVP was attributed to its ability to interact with HPMC chains in the aqueous medium and consequently to reduce the extent of HPMC-HPMC bonding.     

甘露醇添加剂对毛细管无胶筛分电泳分离DNA的影响

在纤维素衍生物筛分体系中加入甘露醇添加剂大大提高了分离能力,在较低筛分剂浓度条件下可得到满意的分离。同时还对甘露醇影响分离的机理做出了解释。     

Design and evaluation of bioadhesive in-situ nasal gel of ketorolac tromethamine

The present study was aimed at developing safe and effective bioadhesive gelling systems of ketorolac tromethamine, a potent non-narcotic analgesic with moderate anti-inflammatory activity for nasal systemic delivery. Chitosan and pectin based gelling systems were prepared with variables like polymer concentration and type. These systems were characterized in terms of their physical properties, in vitro bioadhesion, in vitro drug release and long-term stability. The anti-inflammatory activity and mucosal irritancy of selected gels were also evaluated in rats and these results were compared with per oral, intraperitoneal and nasal solution administration of ketorolac tromethamine. All the prepared formulations gelled immediately at the nasal mucosal pH and showed longer contact time. Addition of hydroxypropyl methylcellulose (HPMC) in both chitosan and pectin based gelling systems increased the viscosity and gel strength. All the formulated gels exhibited pseudoplastic rheology and diffusion-controlled drug release. The results from stability studies revealed that the prepared thermogels showed marginal decrease in viscosity but at the same time, no significant difference in drug content, and in vitro release characteristics were observed before and after accelerated studies. The developed gelling systems produced only mild to negligible irritant effect to nasal mucosae as compared to control group.     

Synthesis and immobilization of micro-scale drug particles in cellulosic films

The anti-solvent synthesis of micron-scale particles, their stabilization, and subsequent self-assembly into polymer films suitable for drug delivery is presented. The colloidal particles were stabilized using low molecular weight hydroxypropyl methylcellulose (HPMC), while drug encapsulation was carried out with high molecular weight HPMC and polyvinylpyrrolidone (PVP). Griseofulvin (GF) was used as the model drug compound, and the polymer films were evaluated in terms of their surface morphology, mechanical properties and in vitro drug release. In general, the release rates were best described by first-order and Hixson-Crowell kinetic models, and in a typical film containing 57% HPMC, 100% of GF was released within 50 min.     

Adjusting drug release by using miscible polymer blends as effective drug carries

In the present study PVP/HPMC and PVP/Chitosan polymer blends were prepared by using the solvent evaporation technique. From DSC studies were revealed that both blends are completed miscible in the entire composition range since only one glass transition temperature was detected. Miscibility can be attributed to the strong interactions evolved between the carbonyl group of PVP, which acts as strong proton acceptor, with hydroxyl and amino-groups of HPMC and Chitosan, which are proton donors. Thus hydrogen bonds are easily formed, as was verified by FTIR, producing miscible blends. However, the extent of interactions depends from polymer composition and mainly from the ratio and the kind of reactive groups. In PVP/HPMC blends a negative variation of T_g is recorded while in PVP/Chitosan the variation has a sigma form. The miscibility of these systems creates matrixes with completely different physical properties in order to use as effective drug carriers. PVP/HPMC blends can be used as pulsatile chronotherapeutics systems adjusting exactly the time of the drug release while PVP/Chitosan blends can be used to control the release profile of a poorly water soluble drug. In these blends HPMC and Chitosan respectively are the control factors for the corresponding applications.     

Rheological characterization of the dilatant flow behavior of highly substituted hydroxypropylmethyl- cellulose solutions in the presence of sodium lauryl sulfate

 The flow behavior of aqueous solutions of three highly substituted, hydrophobic hydroxypropylmethylcelluloses (HPMC) in mixtures containing the anionic surfactant sodium lauryl sulfate (SLS) was investigated both rheo-mechanically and rheo-optically. For the first time it was possible to demonstrate dilatant flow in these systems, a phenomenon which is otherwise only known of some suspensions and associative thickening solutions. Without addition of SLS, the aqueous HPMC solutions showed the predicted flow behavior of polymer solutions, and the Cox–Merz rule was fulfilled. With the addition of SLS to these HPMC solutions, the least hydrophobic HPMC displayed no dilatancy. The solutions of a more hydrophobic HPMC with SLS exhibited on the one hand an increase in viscosity, and on the other hand shear thinning as well as shear thickening. The most hydrophobic HPMC displayed more clearly the effects of an SLS-dependent viscosity increase and the appearance of dilatant flow. At constant HPMC concentration (0.5% w/w), a maximum increase in viscosity (factor 15) was observed in the critical micelle concentration range for SLS. By rheo-optical measurements it was possible to detect an unusually pronounced alignment of the polymer segments as well as a sharp increase in the birefringence values, even before the macroscopic occurrence of dilatant flow. According to the existing network theories, this behavior of the aqueous solutions of highly substituted HPMCs in mixture with SLS has been interpreted as a shear-induced transition from intra-molecular to intermolecular interactions. Received: 4 February 1998 Accepted: 13 March 1998     

Relationship between diffusivity of water molecules inside hydrating tablets and their drug release behavior elucidated by magnetic resonance imaging

We reported previously that sustained release matrix tablets showed zero-order drug release without being affected by pH change. To understand drug release mechanisms more fully, we monitored the swelling and erosion of hydrating tablets using magnetic resonance imaging (MRI). Three different types of tablets comprised of polyion complex-forming materials and a hydroxypropyl methylcellulose (HPMC) were used. Proton density- and diffusion-weighted images of the hydrating tablets were acquired at intervals. Furthermore, apparent self-diffusion coefficient maps were generated from diffusion-weighted imaging to evaluate the state of hydrating tablets. Our findings indicated that water penetration into polyion complex tablets was faster than that into HPMC matrix tablets. In polyion complex tablets, water molecules were dispersed homogeneously and their diffusivity was relatively high, whereas in HPMC matrix tablets, water molecule movement was tightly restricted within the gel. An optimal tablet formulation determined in a previous study had water molecule penetration and diffusivity properties that appeared intermediate to those of polyion complex and HPMC matrix tablets; water molecules were capable of penetrating throughout the tablets and relatively high diffusivity was similar to that in the polyion complex tablet, whereas like the HPMC matrix tablet, it was well swollen. This study succeeded in characterizing the tablet hydration process. MRI provides profound insight into the state of water molecules in hydrating tablets; thus, it is a useful tool for understanding drug release mechanisms at a molecular level.