马来酸氯苯那敏药物树脂复合物制备工艺研究

目的:研究马来酸氯苯那敏药物树脂复合物制备工艺.方法:对静态法从离子交换树脂、药物溶液和盐离子浓度单因素考察,动态法从床高、交换柱直径和药物溶液浓度单因素来考察对制备工艺的影响趋势,并对2种制备工艺进行了优化.结果:静态法工艺简单,而动态法比静态法载药量高.结论:需要根据药物树脂复合物的应用形式来选择具体方法.     

Microencapsulation of phenylpropanolamine to achieve sustained release

Phenylpropanolamine HCl was initially microencapsulated with cellulose acetate butyrate, however, the microcapsules did not show acceptable sustained release. A reduction of the drug particle size prior to microencapsulation resulted in a reduction in drug release rate from the microcapsules. The desired drug release profile was attained only when the drug powder was replaced with a drug-resin complex in the microencapsulation process. The pH of the dissolution media had an effect on the drug release profile.     

Microencapsulation of menthol by crosslinked chitosan via porous glass membrane emulsification technique and their controlled release properties

Chitosan-encapsulated menthol microcapsules were successfully prepared in an oil-in-water (o/w) emulsion using the Shirasu Porous Glass (SPG) membrane emulsification technique and high-speed dispersion technique for preparing a mixed o/w emulsion. The size of the menthol-loaded chitosan microcapsules was strongly depended on the average pore size of the SPG membrane and the amount of menthol loading in the dispersed phase. The membrane pore size of 5.2?µm was suitable for a viscous dispersed phase containing light mineral oil. The average diameter of emulsion droplets of 28.3?µm was obtained. Increasing the menthol loading in the dispersion phase from 5% to 10% w/w of chitosan decreased the emulsion droplet size with a broad size distribution. The crosslinked microcapsule size and size distribution of mixed emulsion droplets decreased with the increasing crosslinking time. The menthol release was a diffusion control which depended on the proportion of amino group in chitosan-to-tripolyphosphate molar ratio and crosslinking time. This work also demonstrated that hydrophilicity/hydrophobicity of the continuous phase and dispersion phase controlled SPG membrane emulsification efficiency and quality of the resulting emulsion droplets.     

Microencapsulation of pheromone-analogue and measurement of the sustained release

Abstract

A model study was conducted to establish 2 feasible production and application systems for the long-term, sustained release of pheromone into the atmosphere of targeted areas. The desired goal of effective release was set at least half a year. 2-Ethylhexyl acetate (EHA) was selected as a pheromone analogue due to its similar structure and easier access for quantitative analysis. At first EHA was impregnated in wax particles, which were then encapsulated employing the complex coacervation of a gelatin-gum arabic system. The release period of EHA through the gelatin wall, however, turned out to be too short—only a week at most. As a second attempt, a modification of the two-phase emulsion technique was employed to encapsulate multiple numbers of wax particles in hydrated networks of gelatin. Though the initial release rate of EHA was still too high, 60 per cent of encapsulated EHA underwent sustained release over six months after absorbed moisture had completely evaporated. A two-step mechanism of mass transfer was proposed and the related parameters in terms of the capacity coefficient and effective diffusion coefficient were estimated.     

Microencapsulation of pheromone-analogue and measurement of the sustained release.

A model study was conducted to establish 2 feasible production and application systems for the long-term, sustained release of pheromone into the atmosphere of targeted areas. The desired goal of effective release was set at least half a year. 2-Ethylhexyl acetate (EHA) was selected as a pheromone analogue due to its similar structure and easier access for quantitative analysis. At first EHA was impregnated in wax particles, which were then encapsulated employing the complex coacervation of a gelatin-gum arabic system. The release period of EHA through the gelatin wall, however, turned out to be too short--only a week at most. As a second attempt, a modification of the two-phase emulsion technique was employed to encapsulate multiple numbers of wax particles in hydrated networks of gelatin. Though the initial release rate of EHA was still too high, 60 per cent of encapsulated EHA underwent sustained release over six months after absorbed moisture had completely evaporated. A two-step mechanism of mass transfer was proposed and the related parameters in terms of the capacity coefficient and effective diffusion coefficient were estimated.     

Microencapsulation with carrageenan-locust bean gum mixture in a multiphase emulsification technique for sustained drug release

Abstract

A multiphase emulsification technique was modified in this process of microencapsulating gentamicin sulphate, thus avoiding the necessity for a surfactant in preparing the secondary emulsion for a W/O/W emulsion. Various proportions of iota-carrageenan (i-C) and locust bean gum (LBG) were investigated for the W/O/W emulsion after forming the primary W/O emulsion with sorbitan trioleate, Span 85. Upon removal of the oil phase (chloroform) from the W/O/W emulsion by heating (60-65°C), microcapsules or ‘W/W particles containing drug dissolved in sodium hyaluronate were spontaneously formed. These were dispersed in a solution of a mixture of 5-10 per cent w/v polyvinyl alcohol, PVA (average MW 50000-106000; 98 per cent hydrolysed) and 3 per cent v/v polyethylene glycol 200 (PEG 200), and dried to form the hydrogel film casts. Our in vitro experiments in isotonic phosphate buffer solution (pH 7-4) at 37°C., showed that the release of gentamicin sulphate was dependent on concentration of LBG, and concentration or molecular weight of PVA. With the exception of PVA hydrogel matrix preparations containing 20 per cent w/v LBG, all other formulations showed a significant initial ‘burst' release of drug within 6h. The drug-containing microcapsules in the PVA hydrogel film with 20 per cent w/v LBG, exhibited an almost zero-order release of drug up to 140h. It is postulated that an effective barrier or high-density membrane enveloping the microcapsules was formed between i-C and LBG because of their unique molecular configurations. This phenomenon, together with the possible adsorption of i-C molecules at the transient oil and outer aqueous phase interface, presumably eliminated the need for a permanent oil phase and/or an O/W surfactant normally required for preparing W/O/W emulsions.     

Preparation and characterization of bee venom-loaded PLGA particles for sustained release

Abstract

Bee venom-loaded poly(lactic-co-glycolic acid) (PLGA) particles were prepared by double emulsion-solvent evaporation, and characterized for a sustained-release system. Factors such as the type of organic solvent, the amount of bee venom and PLGA, the type of PLGA, the type of polyvinyl alcohol, and the emulsification method were considered. Physicochemical properties, including the encapsulation efficiency, drug loading, particle size, zeta-potential and surface morphology were examined by Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction (XRD). The size of the bee venom-loaded PLGA particles was 500?nm (measured using sonication). Zeta-potentials of the bee venom-loaded PLGA particles were negative owing to the PLGA. FT-IR results demonstrated that the bee venom was completely encapsulated in the PLGA particles, indicated by the disappearance of the amine and amide peaks. In addition, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis indicated that the bee venom in the bee venom-loaded PLGA particles was intact. In vitro release of the bee venom from the bee venom-loaded PLGA particles showed a sustained-release profile over 1 month. Bee venom-loaded PLGA particles can help improve patients’ quality of life by reducing the number of injections required.     

一种新型蛋白缓释载体——两亲性壳聚糖衍生物的研究

目的:研究两亲性壳聚糖衍生物N-辛基-O, N-羟乙基壳聚糖(OGC)分子量和辛基取代度不同对牛血清蛋白(BSA)的负载及其释放行为的影响.方法:制备BSA-OGC纳米胶束;高速冷冻离心和荧光法测定包封率和载药量,并测定粒径、Zeta-电位;在PBS 7.4(37 ℃)中测定BSA-OGC纳米胶束的体外释放行为;用SDS-PAGE明胶电泳考察BSA在纳米胶束体外释放过程中的稳定性.结果:辛基取代度越高,BSA的包封率和载药量越小,且释放越慢;分子量对BSA的负载影响不大,但BSA的释放会随着分子量的增加而变慢;OGC可保证BSA在释放过程中的稳定性.结论:两亲性壳聚糖衍生物OGC可作为优良的蛋白缓释载体.     

交联甲壳胺-PEG-尼莫地平缓释颗粒性质及释药特性

目的研究交联甲壳胺PEG尼莫地平(rosslinked chitosan PEG nimodipine,RCPN)缓释颗粒的性质及体外释药特性。方法采用乳化交联法制备交联甲壳胺PEG尼莫地平缓释颗粒;用红外光谱(IR)对其结构进行表征;扫描电子显微镜(SEM)观察颗粒形态及表面结构;考察颗粒的粒径分布、颗粒中药物含量测定及在不同介质中药物的释放。结果电镜扫描显示颗粒呈球形,表面圆整,个别表面有凹凸状;RCPN缓释颗粒平均粒径为1.20 mm;红外图谱显示甲壳胺的氨基和戊二醛的羰基发生反应生成Schiffs碱。该颗粒剂有缓释作用,释药特性符合Higuchi方程。结论以交联甲壳胺做为辅料制备的缓释颗粒在体外具有缓释作用。     

Therapeutic efficacy of sustained drug release from chitosan gel on local inflammation

The model anti-inflammatory drug prednisolone (PS) was retained in chitosan (CS) gel beads, which were prepared in a 10% aqueous amino acid solution (pH 9.0). Sustained release of PS from the CS gel beads was observed. Carrageenan solution was injected into air pouches (AP), which were prepared subcutaneously on the dorsal surface of mice, in order to induce local inflammation. CS gel beads retaining PS were then implanted into the AP to investigate the therapeutic efficacy of sustained PS release against local inflammation. In vivo PS release from CS gel beads was governed by both diffusion of the drug and degradation of the gel matrix. Sustained drug release by CS gel beads allowed the supply of the minimum effective dose and facilitated prolonged periods of local drug presence. Inflammation indexes were significantly reduced after implantation of CS gel beads when compared with injection of PS suspension. Thus, extension of the duration of drug activity by CS gel beads resulted in improved therapeutic efficacy. These observations indicate that CS gel beads are a promising biocompatible and biodegradable vehicle for treatment of local inflammation.     

In vitro and in vivo evaluation of thermosensitive chitosan hydrogel for sustained release of insulin

Injectable In situ gel-forming chitosan/β-glycerol phosphate (CS/β-Gp) solution can be introduced into the body in a minimally invasive manner prior to solidifying within the target tissue. This hydrogel is a good candidate for achieving a prolonged drug delivery system for insulin considering its high molecular weight. In addition to the physicochemical characterization of this hydrogel, in vitro and in vivo applications were studied as a sustained insulin delivery system. In the in vitro release studies, 19–63% of total insulin was released from the CS/β-Gp hydrogel within 150?h at different β-Gp and insulin concentrations. The best formulation was selected for in vivo experimentation to control the plasma glucose of diabetic mice models. The hypoglycemic effect of this formulation following subcutaneous injection in diabetic mice lasted 5?d, significantly longer than that of free insulin solution which lasted several hours.     

Properties of sustained release hot-melt extruded tablets containing chitosan and xanthan gum

The aim of this study was to investigate the influence of pH, buffer species and ionic strength on the release mechanism of chlorpheniramine maleate (CPM) from matrix tablets containing chitosan and xanthan gum prepared by a hot-melt extrusion process. Drug release from hot-melt extruded (HME) tablets containing either chitosan or xanthan gum was pH and buffer species dependent and the release mechanisms were controlled by the solubility and ionic properties of the polymers. All directly compressed (DC) tablets prepared in this study also exhibited pH and buffer species dependent release. In contrast, the HME tablets containing both chitosan and xanthan gum exhibited pH and buffer species independent sustained release. When placed in 0.1N HCl, the HME tablets formed a hydrogel that functioned to retard drug release in subsequent pH 6.8 and 7.4 phosphate buffers even when media contained high ionic strength, whereas tablets without chitosan did not form a hydrogel to retard drug release in 0.1N HCl. The HME tablets containing both chitosan and xanthan gum showed no significant change in drug release rate when stored at 40 °C for 1 month, 40 °C and 75% relative humidity (40 °C/75% RH) for 1 month, and 60 °C for 15 days.     

依诺沙星缓释颗粒在兔眼内的药动学

目的 :观察聚乳酸 聚乙醇酸共聚物依诺沙星缓释颗粒植入兔眼内的药物释放过程。方法 :以高分子量的聚乳酸 聚乙醇酸共聚物为载体制得含药量为 30 %的依诺沙星缓释颗粒 ,并作体外药物释放度实验。将该缓释颗粒植入兔眼前房中 ,以高效液相色谱法在不同时间点做药物浓度测定。结果 :体外 4d内依诺沙星缓释制剂累积释放率为 6 .37% ,兔眼房水内 5d药物浓度变化范围 1.2 1～ 10 .2 2mg·L-1,远高于最小抑菌浓度。该缓释颗粒在兔眼房水内的药动学参数分别为T1/ 2 (Ka)0 .0 4 5h ,T1/ 2 (Ke) 2 4 .5 5h ,Tmax0 .4 1h ,Cmax9.18mg·L-1,AUC 32 8.96mg·h·L-1。结论 :该聚合物制备的依诺沙星缓释颗粒具有良好的缓释作用 ,在兔眼内药动学特点符合眼内炎抗菌药治疗的基本要求。     

Microencapsulation of dissociable human growth hormone aggregates within poly(D,L-lactic-co-glycolic acid) microparticles for sustained release

For the sustained release formulation of recombinant human growth hormone (rhGH), dissociable rhGH aggregates were microencapsulated within poly(D,L-lactic-co-glycolic acid) (PLGA) microparticles. rhGH aggregates were first produced by adding a small volume of aqueous rhGH solution into a partially water miscible organic solvent phase (ethyl acetate, EtAc) containing PLGA. These rhGH aggregates were then microencapsulated within PLGA polymer phase by extracting EtAc into an aqueous phase pre-saturated with EtAc. Release profiles of rhGH from these microparticles were greatly affected by changing the volume of incubation medium. The released rhGH species consisted of mostly monomeric form having a correct conformation. This study reveals that sustained rhGH release could be achieved by microencapsulating reversibly dissociable protein aggregates within biodegradable polymers.     

Chlorogenic acid loaded chitosan nanoparticles with sustained release property,retained antioxidant activity and enhanced bioavailability

In this study, chlorogenic acid (CGA), a phenolic compound widely distributed in fruits and vegetables, was encapsulated into chitosan nanoparticles by ionic gelation method. The particles exhibited the size and zeta potential of 210 nm and 33 mV respectively. A regular, spherical shaped distribution of nanoparticles was observed through scanning electron microscopy (SEM) and the success of entrapment was confirmed by FTIR analysis. The encapsulation efficiency of CGA was at about 59% with the loading efficiency of 5.2%. In vitro ABTS assay indicated that the radical scavenging activity of CAG was retained in the nanostructure and further, the release kinetics study revealed the burst release of 69% CGA from nanoparticles at the end of 100th hours. Pharmacokinetic analysis in rats showed a lower level of C_max, longer T_max, longer MRT, larger AUC_0–t and AUC_0–∞ for the CGA nanoparticles compared to free CGA. Collectively, these results suggest that the synthesised nanoparticle with sustained release property can therefore ease the fortification of food-matrices targeted for health benefits through effective delivery of CGA in body.     

Comparison of the hematological effects of a sustained release chitosan formulation of pentoxifylline with a commercial formulation

In the present study the hematological effects of a sustained release chitosan formulation of pentoxifylline (CAS 6493-05-6) were examined and compared with those of a commercial product. The study was carried out on 12 healthy volunteers. Both formulations were tolerated well clinically. The results demonstrated no antiaggregatory effect of the two different formulations of pentoxifylline in platelet rich plasma. Both drugs resulted in a decrease of plasma fibrinogen levels. A remarkable side effect of the new formulation was mild basophilia, without any clinical problems.     

Semi-IPN chitosan/polyvinylpyrrolidone microspheres and films: sustained release and property optimisation

Abstract

A set of chitosan-polyvinylpyrrolidone (CH-PVP) microspheres were prepared as semi-inter penetrating networks (semi-IPN) and loaded with 5-fluorouracil. In vitro release studies showed faster release for semi-IPN microspheres compared to pure CH samples, and the total release was achieved in about 20–30 days, depending on the composition. In vitro cell studies were achieved against human breast adenocarcinoma cell line cells where adsorption of cells on microspheres with a significant decrease in their number was obtained. Meanwhile, the CH-PVP films, which were prepared with the same compositions as in the microspheres, demonstrated an increase in strength from 66 to 118?MPa as the PVP content was decreased. It can be concluded that the prepared CH-PVP semi-IPN microspheres are novel promising carriers compared to pure CH microspheres since it becomes possible to adjust stability and hydrophilicity of the microspheres as well as the release rates of the drugs from the microspheres by changing the ratio of CH/PVP composition.     

Coating of multiparticulates for sustained release

Multiparticulates are discrete particles that make up a multiple-unit system. They provide many advantages over single-unit systems because of their small size. Studies have shown that multiparticulates are less dependent on gastric emptying, resulting in less inter- and intra-subject variability in gastrointestinal transit time. They are also better distributed and less likely to cause local irritation. The drug dose in a multiple-unit system is divided over the multiparticulates that make up that system. As such, failure of a few units may not be as consequential as failure of a single-unit system. Multiparticulates may be prepared by several methods. Different methods require different processing conditions and produce multiparticulates of distinct qualities. Some of these methods may be broadly classified as pelletization, granulation, spray drying, and spray congealing. Drug particles may be entrapped within the multiparticulates or layered around them. Subsequently, these multiparticulates may be modified in many ways to achieve the desired drug-release profile. One approach to the modification of drug-release profiles in multiparticulates is to coat them. Reasons for the application of coating onto multiparticulates are to obtain functional coats, provide chemical stability, improve physical characteristics, and enhance patient acceptance. Coats are formed from various polymeric coating materials broadly classified as aqueous polymer dispersions, polymer solutions, molten polymers, and dry powders. Depending on the type of coating material used, functions such as sustained release (SR), targeted release, delayed release, and pulsatile release can be achieved. The focus of this review is on SR coating. The most common method used for the application of coating onto multiparticulates is air suspension coating. Other methods include compression coating, solvent evaporation, coacervation, and interfacial complexation. It is also possible to form coated microparticles by spray drying and spray congealing. A major part of this review is focused on factors affecting the coating of multiparticulates and drug-release characteristics from SR coated multiparticulates. Knowledge of these factors is important in the development of SR coated multiparticulates because control of these factors ensures consistency of drug release between batches of multiparticulates. These factors may be classified into four groups: characteristics of cores, characteristics of SR coats, coating equipment, and coating process conditions.     

Development of spherical iron(II) sulfate heptahydrate-containing solid particles with sustained drug release.

The aim of this work was to develop a simple, economic procedure for the manufacturing of coated iron(II) sulfate particles by using a crystallization technique for the development of round particles, followed by coating with a lipophilic material. Several batches of iron(II) sulfate heptahydrate were produced by a cooling crystallization, with variation of the crystallization parameters. The spherical crystals were coated with stearin. The products were characterized for particle size, roundness, bulk density and in vitro drug dissolution. Crystallization was performed from deionized water with no addition of seed crystals and by cooling by applying a linear cooling rate. The developed iron(II) sulfate crystals were round with average diameter of 729+/-165 microm. The best form for the sustained release of iron(II) sulfate was the sample HTP-2 which contained 11% of stearin relative to the iron(II) sulfate. The spherical crystallization of iron(II) sulfate is simple and fast, and does not require a dangerous, expensive solvent. The round particles can coat directly with lipophilic material which results in slow release of iron(II) sulfate and protects the iron(II) from oxidation and inhibits the loss of crystal water. The coated crystals can be filled into capsules to yield the final dosage form.     

Optimization of levofloxacin-loaded crosslinked chitosan microspheres for inhaled aerosol therapy

The aim of this work was the development of innovative levofloxacin-loaded swellable microspheres (MS) for the dry aerosol therapy of pulmonary chronic Pseudomonas aeruginosa infections in Cystic Fibrosis patients. In a first step, a factorial design was applied to optimize formulations of chitosan-based MS with glutaraldehyde as crosslinker. After optimization, other crosslinkers (genipin, glutaric acid and glyceraldehyde) were tested. Analyses of MS included aerodynamic and swelling properties, morphology, drug loading, thermal and chemical characteristics, in vitro antibacterial activity and drug release studies. The prepared MS presented a drug content ranging from 39.8% to 50.8% of levofloxacin in an amorphous or dispersed state, antibacterial activity and fast release profiles. The highest degree of swelling was obtained for MS crosslinked with glutaric acid and genipin. These formulations also presented satisfactory aerodynamic properties, making them a promising alternative, in dry-powder inhalers, to levofloxacin solution for inhalation.