美托拉宗缓释片的制备和释药机制的研究

目的 制备美托拉宗缓释片并探讨其释药机制.方法从处方和工艺两个方面考察了各因素对药物释放行为的影响.在单因素考察的基础上,采用羟丙甲基纤维素(HPMC)4000 cps作为骨架材料HPMC 5 cps作为致孔剂,制备美托拉宗缓释片.通过正交设计,以2、4、7 h的药物释放度为评价指标,优化最佳处方.结果HPMC的用量和...     

Sustained release of hydrophobic and hydrophilic drugs from a floating dosage form

Floating dosage forms enable the sustained delivery of drugs in the gastro-intestinal tract. In this study, a type of multi-unit floating gel bead was synthesized with calcium alginate, sunflower oil, and a drug of interest through an emulsification/gelation process. The alginate beads with oil addition were able to continuously float over the medium for 24h under constant agitation while the non-oily beads could not. Three kinds of drugs with different hydrophilicities, ibuprofen, niacinamide and metoclopramide HCl, were tested in the study. The hydrophobic drug ibuprofen was released in a sustained manner for 24h, due to the oil partitioning. With suitable modification, the beads were able to also release the hydrophilic drugs, niacinamide and metoclopramide HCl, for a similar duration. Therefore a floating dosage form that is able to sustain release both hydrophobic and hydrophilic drugs within its extended gastric retention time has been developed.     

Sustained release of antineoplastic drugs from chitosan-reinforced alginate microparticle drug delivery systems

Alginate based microparticle drug delivery systems were prepared for the sustained release of antineoplastic drugs. Two drugs, 5-fluorouracil (5-FU) and tegafur, were encapsulated into the microparticles. The drug loaded microparticles were fabricated using a very convenient method under very mild conditions, i.e., directly shredding the drug loaded beads into microparticles in a commercial food processor. The mean sizes of the obtained microparticles were between 100 and 200 μm. To effectively sustain the drug release, alginate microparticles were reinforced by chitosan during gelation. The drug release from the chitosan-reinforced alginate microparticles was obviously slower than that from the unreinforced microparticles. The effect of the reinforcement conditions on the drug release property of the microparticles was studied, and the optimized concentration of chitosan solution for reinforcement was identified. The effects of drug feeding concentration and pH value of the release medium on the drug release were investigated.     

Modifying matrix micro-environmental pH to achieve sustained drug release from highly laminating alginate matrices

Lamination of alginate matrix tablet at acidic pH can compromise its function as a sustained release carrier. This phenomenon is associated with the conversion of sodium alginate to alginic acid. An innovative approach for controlling the release of a highly water-soluble drug from such matrices is presented in this paper. Inclusion of pH-modifiers was employed to raise the micro-environmental pH within matrices undergoing dissolution at gastric pH. The changes in micro-environmental pH of hydrating alginate matrices were visualized with the aid of a pH-indicator and subsequently quantified using image analysis. Transient elevation in micro-environmental pH impeded alginate protonation and minimized or prevented matrix lamination, contributing to preservation of drug diffusion barrier. Significant reduction in the rate of drug release at pH 1.2 was achieved in the presence of such additives. The action of pH-modifiers was synergistically enhanced in the presence of a carbon dioxide barrier formed by effervescing sodium bicarbonate, reducing drug release in the acidic medium from 60 to 20%. Further insight into the influence of lamination on drug release from alginate compacts was given.     

Release characteristics of chitosan treated alginate beads: II. Sustained release of a low molecular drug from chitosan treated alginate beads

The aim of this paper was to investigate the possible applicability of chitosan treated alginate beads as a controlled release system of small molecular drugs with high solubility. Timolol maleate (mw 432.49) was used as a model drug. The beads were prepared by the ionotropic gelation method and the effect of various factors (alginate, chitosan, drug and calcium chloride concentrations, the volume of external and internal phases and drying methods) on bead properties were also investigated. Spherical beads with 0.78-1.16mm diameter range and 10.8-66.5% encapsulation efficiencies were produced. Higher encapsulation efficiencies and retarded drug release were obtained with chitosan treated alginatebeads. Amongthedifferentfactors investigatedsuchas alginate, drug, chitosan and CaCl₂ concentrations, the volumes of the external and internal phases affected bead properties. The drying technique has an importance on the bead properties also. The release data was kinetically evaluated. It appeared that chitosan treated alginate beads may be used for a potential controlled release system of small molecular drugs with high solubility, instead of alginate beads.     

马来酸曲美布汀缓释片体外释放特征与体内J＇b~H关性研究

目的考察马来酸曲美布汀缓释片体外药物释放特征与体内外相关性。方法分别采用①水、②0．1mol／L盐酸、③0．01mol／L盐酸等三种溶剂作为释放介质,考察释放介质对释放度的影响。用Wagner—Nelson方程法计算马来酸曲美布汀缓释片在健康男性受试者体内吸收百分数,并与相应时间体外累积释放度线性回归,进行体内外相关性考察。结果马来酸曲美布汀缓释片在不同释放介质中的释放度一致,均符合零级动力学。将体内累积吸收百分数y与相应时间在0．01mol／L盐酸释放介质中的体外释放百分数X进行线性回归（n=7）,回归方程为Y=1．0093x一0．3329,r：0．9600（P=0．000601〈0．001）,表明具有良好的体内外相关性,呈A级相关。结论马来酸曲美布汀缓释片的释放度不受三种释放介质影响,释药恒速。体外释放累积百分数与体内吸收百分数呈A级相关。     

壳聚糖/海藻酸钠自组装微球的制备及释药性能

目的利用壳聚糖(CS)聚阳离子及海藻酸钠(ALG)聚阴离子电解质的性质,在药物微球表面自组装形成多层包覆结构的壳聚糖载药微球,并研究组装层数、温度及盐离子浓度对自组装微球释药性能的影响。方法采用乳化交联法制备CS载四环素(TC)的药物微球,并在其表面交替自组装ALG及CS。利用IR测试技术及电极电位法进行表征。结果CS交联微球未破坏CS及TC的结构,CS与ALG以静电作用相结合。CS交联微球的载药量为40.2%,自组装六层的微球载药量为32%。组装后,药物释放时间延长,初期暴释现象得到极大改善,释药速率随组装层数的增加而下降,温度较高时组装完整,盐离子浓度存在较佳点。结论温度为60℃、盐离子浓度为0.5 mol.L-1、组装层数为四层的微球释药性能较佳。     

Alginate encapsulated mesoporous silica nanospheres as a sustained drug delivery system for the poorly water-soluble drug indomethacin

We applied a combination of inorganic mesoporous silica material, frequently used as drug carriers, and a natural organic polymer alginate (ALG), to establish a sustained drug delivery system for the poorly water-soluble drug Indomethacin (IND). Mesoporous silica nanospheres (MSNs) were synthesized using an organic template method and then functionalized with aminopropyl groups through postsynthesis. After drug loading into the pores of aninopropyl functionalized MSNs (AP-MSNs), IND loaded AP-MSNs (IND-AP-MSNs) were encapsulated by ALG through the ionic interaction. The effects of surface chemical groups and ALG layer on IND release were systematically studied using scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption, zeta-potential analysis and TGA analysis. The surface structure and surface charge changes of the ALG encapsulated AP-MSNs (ALG-AP-MSNs) were also investigated. The results showed that sustained release of IND from the designed drug delivery system was mainly due to the blockage effect from the coated ALG. We believe that this combination will help designing oral sustained drug delivery systems for poorly water-soluble drugs.     

市售盐酸氨溴索缓释胶囊的体外释放度比较

目的：比较不同厂家盐酸氨溴索缓释胶囊的体外释放度.方法：按标准要求对国内外4个厂家生产的盐酸氨溴索缓释胶囊的释放度进行测定,并用Excel软件进行释药曲线拟合,比较溶出参数（m,Td）差异性.结果：四个厂家产品的释药曲线存在显著差异,曲线均符合威布尔方程,A厂的释放曲线零级方程拟合相关系数更高.结论：不同厂家的盐酸氨溴索缓释胶囊的体外释放度存在差异,为临床用药提供一定参考.     

Investigations on mefenamic acid sustained release tablets with water-insoluble gel

Mefenamic acid (MA) has analgesic, anti-inflammatory and antipyretic properties. Available conventional dosage forms are capsules and film-coated tablets. No commercial sustained release preparation of MA exists in the market. The usual oral dose is 250 or 500 mg and reported half-life is 2 h. Sodium alginate (NaAL) is the sodium salt of alginic acid, a natural polysaccharide extracted from marine brown algae. It has the ability to form a water-insoluble gel with a bivalent metal ions as calcium. Therefore, NaAL has been studied for preparing sustained release formulations in pharmaceutical technology. In this study, tablet formulations containing different ratios of NaAL and calcium gluconate (CaGL) were prepared by direct compression method. In vitro release studies were carried out using USP 23 basket method and release data were kinetically evaluated. According to release studies, it can be emphasized that NaAL and CaGL can be used for design of sustained release preparation of MA.     

The relationship between mucoadhesive polymers and surface coating in tablets for the controlled colonic delivery of a poorly water-soluble drug

BackgroundThe mucoadhesive polymers play an important role in targeted and controlled drug delivery.ObjectivesThis study aimed to investigate the drug release behaviour and interpret the role of mucoadhesive polymers involved in the coating layer of mucoadhesive tablets for the sustained release of a poorly water-soluble drug.MethodsA solid dispersion of prednisolone and zein was used in the core tablets created with two mucoadhesive polymers, which included Carbopol 940 and hydroxypropyl methylcellulose K4M. In addition, the properties of a single-layer coating, created from the combination of zein and Kollicoat MAE 100P to delay release through the upper parts of the gastrointestinal tract, were investigated in the presence of the above mucoadhesive polymers; these properties included drug dissolution, mucoadhesion, surface morphology, swelling and erosion.ResultsThe mucoadhesive polymer concentrations and types were integrated not only into the core tablets through a swelling/erosion mechanism but also into the surface polymer coatings for controlled drug release. HPMC was preferred in the formulations due to the ability to form pores on the surface coating, allowing water uptake so that the coating could control drug release for a later stage via a swelling/erosion mechanism.ConclusionThe proposed mechanism determined in this project could be beneficial in the selection of polymers for applications targeting the colon with coated mucoadhesive tablets. Open in a separate windowGraphical abstract     

Biphasic drug release from film-coated tablets

A study was carried out into the biphasic drug release properties of film-coated paracetamol tablets. The tablet cores were formulated without a disintegrant and film-coated with a coating formulation consisting of pectin, chitosan and hydroxypropylmethylcellulose in a ratio of 6:1:0.37. The tablet cores and the film-coated tablets with coat weight gains (CWGs) of 6, 9 and 13% were evaluated for their water absorption (swelling) and drug release properties. All the tablets absorbed water from pH 6.0 Sorensen's phosphate buffer and the amount of water absorbed increased with an increase in tablet CWG. The addition of 100 μl/50 ml pectinolytic enzymes to the medium resulted in at least a 40% reduction in the amount of water absorption by the tablets, as compared to the medium without enzymes. When the enzyme concentration was increased to 200 μl/50 ml, there was a further reduction (8% w/w) in the amount of water absorbed by the tablets. Drug release was controlled in upper gastrointestinal fluids and decreased with an increase in tablet CWG. Drug release was, however, accelerated in the presence of pectinolytic enzymes, consistent with the entry of the tablets in the colon. An evaluation of the drug release data by the Korsmeyer–Peppas equation showed the involvement of molecular diffusion and other factors such as film/tablet erosion and drug dissolution in drug release.     

对乙酰氨基酚非pH依赖性缓释片的处方优化

目的:设计及优化非pH依赖性缓释片处方.方法:以对乙酰氨基酚为模型药物,设计不同配比的海藻酸钠和壳聚糖为混合骨架的缓释片处方,测定各处方在 0.1 mol·L-1盐酸和pH 6.8磷酸盐缓冲液中的释放度,采用多指标同步优化筛选处方.结果:优化的乙酰氨基酚缓释片处方含壳聚糖 85 mg、海藻酸钠 135 mg 时,呈现良好的体外非pH依赖性释放特征.结论:采用海藻酸钠和壳聚糖混合骨架易制得非pH依赖性缓释片,且方法简单、成本低,具有较高的实用价值.     

HPLC测定利巴韦林缓释片的含量

目的　建立利巴韦林缓释片的含量测定方法。方法　采用HPLC ,C1 8色谱柱 ,进口填料 (5 μm ,1 5 0mm× 4 6mm) ,检测波长 2 0 7nm ,流动相为水。结果　进样量在 0 2～ 0 8μg范围内线性关系良好 (r =0 9999) ,回收率平均值为 99 1 % ,RSD =1 1 1 % (n =9)。结论　所用方法简便 ,准确 ,重复性好。     

Polyelectrolyte-coated alginate microspheres as drug delivery carriers for dexamethasone release

Alginate microspheres loaded with dexamethasone were prepared by the droplet generator technique. Important parameters affecting drug release, including initial drug content, the type of polyelectrolyte coating, and a combination of different ratios of coated and uncoated microspheres were investigated to achieve in vitro dexamethasone delivery with approximately zero order release kinetics, releasing up to 100% of entrapped drug within 1 month, wherein dexamethasone released at a steady rate of 4.83 μg/day after an initial burst release period. These findings imply that these polyelectrolyte-coated alginate microspheres show promise as release systems to improve biocompatibility and prolong lifetime of implantable glucose sensors.     

洛索洛芬钠缓释片的制备

目的：考察不同因素对洛索洛芬钠缓释片体外释放的影响。方法在缓冲液中测定 HPC、mCC、HPmC、压力等因素对缓释片释放速率的影响。结果随着 HPmC、HPC 用量的增加洛索洛芬钠缓释片释药减慢,但随着 mCC 用量增加溶出速率增加,累积释放量亦有明显改善,压力增大释放减慢,但影响不明显。结论通过调节洛索洛芬钠缓释片可以得到满意的释放效果。     

pH-dependent release property of alginate beads containing calcium carbonate particles

Alginate bead containing calcium carbonate particle were prepared by dropping the suspension of alginate/calcium carbonate (4/1, w/w) into aqueous solution of CaCl₂ (0.1?M). The pH-dependent release property of the bead was observed for 12?h using blue dextran as a model drug. The release increased up to 4?h in a saturation manner. When no calcium carbonate was contained, the release exhibited no marked variation with pH and the values were 27–39%. On the other hand, in case calcium carbonate was included in the matrix of alginate beads, intensive release(40–50%) was achieved in acidic and neutral conditions and the degrees of release were suppressed in alkali conditions and the values were ～20%. The pH-sensitive release property is possibly because the particles of calcium carbonate embedded in the matrix of beads were leached out in acidic and neutral conditions, leaving cavities in the matrix. The cavities are likely to be main pathways for the release of blue dextran.     

Sustained release of brimonidine from BRI@SR@TPU implant for treatment of glaucoma

Glaucoma is the leading cause of irreversible vision loss worldwide, and reduction of intraocular pressure (IOP) is the only factor that can be interfered to delay disease progression. As the first line and preferred method to treat glaucoma, eye drops have many shortcomings, such as low bioavailability, poor patient compliance, and unsustainable therapeutic effect. In this study, a highly efficient brimonidine (BRI) silicone rubber implant (BRI@SR@TPU implant) has been designed, prepared, characterized, and administrated for sustained relief of IOP to treat glaucoma. The in vitro BRI release from BRI@SR@TPU implants shows a sustainable release profile for up to 35 d, with decreased burst release and increased immediate drug concentration. The carrier materials are not cytotoxic to human corneal epithelial cells and conjunctival epithelial cells, and show good biocompatibility, which can be safely administrated into rabbit’s conjunctival sac. The BRI@SR@TPU implant sustainably released BRI and effectively reduced IOP for 18 d (72 times) compared to the commercial BRI eye drops (6 h). The BRI@SR@TPU implant is thus a promising noninvasive platform product for long-term IOP-reducing in patients with glaucoma and ocular hypertension.     

Sustained release properties of alginate microspheres and tabletted microspheres of diclofenac sodium

This study focused on the properties of diclofenac sodium (DNa) alginate (alg) microspheres and tabletted DNa alg microspheres using different polymers as additives. DNa alginate microspheres were prepared by the emulsification method and different polymers such as Eudragit (Eud) NE 30 D, Eudragit (Eud) RS 30 D and Aquacoat, which were incorporated into alg gel to control the release rate of drug. The release properties of DNa alg microspheres (1:1) were affected by the size, drug load of microspheres and also by the incorporated polymers, pH and ionic strength of dissolution medium. Tabletting of alg microspheres using carrageenan (carr), alg, pectin, NaCMC, tragacanth (trgh) and HPMC as additives in a (50:50) ratio produced tablets with good physical properties and also better controlled release of DNa. Dissolution studies were carried out in pH7.2 phosphate buffer and phosphate buffers whose pH values were gradually changed from pH 3 to 7.4. The rank order of DNa release from tablets was carr<alg<pectin<NaCMC<trgh<HPMC which relates to the viscosity and swelling properties of polymers. The drug release was very slow from trgh and HPMC based tablets, but addition of carr or alg in different ratios could adjust the release rate of drug.     

Importance of drug type, tablet shape and added diluents on drug release kinetics from hydroxypropylmethylcellulose matrix tablets

The dissolution of 7 drugs from hydroxypropylmethylcellulose (HPMC) matrices have been examined to determine the time exponent (tⁿ) required to produce linear dissolution profiles. A value of n = ˜ 0.67 was obtained for time-dependent release for soluble drugs, the precise values being 0.71, 0.65, 0.67 and 0.64 for promethazine hydrochloride, aminophylline, propranolol hydrochloride and theophylline, respectively. The insoluble drugs, indomethacin and diazepam, displayed values of n = 0.90 and 0.82 indicating a near zero-order release. Matrices containing tetracycline hydrochloride, however, showed a value of n = 0.45 and displayed complex release patterns and lower release rates than anticipated on the basis of solubility. Replacement of HPMC by calcium phosphate or lactose increased the dissolution rates of promethazine hydrochloride although the values of n were unchanged. Differences in release rates between lactose and calcium phosphate replacement occurred only when matrices contained high levels of the diluents. A straight line relationship existed between release rates and tablet surface area for HPMC tablets containing promethazine hydrochloride.