肠靶向海藻酸钙基微胶囊的制备及控释性能研究

利用毛细管共挤出技术结合静电吸附和仿生硅化的方法，制备了海藻酸钙-壳聚糖/精蛋白/二氧化硅(ACPSi)复合微胶囊。ACPSi复合微胶囊的平均粒径约3.18 mm，单分散性好，囊壁最外层的二氧化硅层可抑制其在肠液pH环境中的溶胀，增强囊的机械稳定性。将羟丙甲基纤维素邻苯二甲酸酯(HPMCP)肠溶微球作为释药“微阀门”，嵌入囊壁可以更好地控制微胶囊的释药行为。以吲哚美辛为模型药物，当药物浓度为22.5 mg/ml时，ACPSi载药微胶囊在pH 2.5模拟胃液中3 h时累计释药率仅为0.33%，而转移至pH 6.8模拟肠液中19 h时累计释药率为77.78%；囊壁嵌入HPMCP微球后，22 h时累计释药率可提高约4%。因此，该复合微胶囊具有良好的肠靶向作用和控释特性，作为口服肠靶向缓控释制剂具有良好的应用前景。     

Low surface energy self-polishing polymer grafted MWNTs for antibacterial coating and controlled-release property of Cu2O

Marine biofouling had been a headache when engaging in marine activities. The most effective and convenient method for dealing with this problem was to apply antifouling coatings. But now a single anti-fouling system was hard to satisfy the requirement of anti-fouling simultaneously. Therefore, it was particularly important to develop novel multi-system anti-fouling technology. In the work, a novel polymer coatings with polydimethylsiloxane (PDMS) segments in the main chain and hydrolysable side chain was designed and synthesized which showed low surface energy and self-polishing performance, and then we creatively covalently immobilized the polyurethane on the surface of multi-carbon nanotubes (MWNTs) to form multisystem antifouling coating. The results showed that the polymer coating would produce hydrolysable regions in the hydrophobic PDMS segment to endure the polymer coating hydrophobic and hydrolysis properties when contacted with water. In addition, the self-polishing rate and the surface energy could be regulated by varying its copolymerization, and the addition of MWNTs could kill the microorganisms and endowed the polymer coating itself enhanced antibacterial effect. Furthermore, considering the high specific surface area and physicochemical characteristics of MWNTs, it could be combined with antifoulant Cu₂O through a polar or non-polar combination as a carrier to control the release rate of Cu₂O in coatings.     

“Rolling” phenomenon in twin screw granulation with controlled-release excipients

The developed knowledge regarding use of twin screw granulators for continuous wet granulation has been primarily limited to immediate release formulations in the literature. The present study highlights an issue previously unreported for wet granulation with twin screw extruders when using formulations containing controlled-release (CR) excipients. Long (3–10?mm), twisted noodle-like granules can be produced in the presence of these excipients that are difficult to control and are anticipated to create complications in downstream unit operations to the granulator. Working with two different CR excipients, METHOCEL? K4M and Kollidon® SR, each blended at different ratios with a mixture of 80% α-lactose monohydrate/20% microcrystalline cellulose, these unique particles were found to be produced in the conveying elements of the extruder, arising from a rolling action at the top of the screw flights. The CR excipients adhesively strengthen the wetted mass, forming this undesired granule shape such that they persisted to the exit of the machine; the shape appeared most strongly affected by screw speed, producing particles of higher aspect ratio as speed was increased. Adjusting the concentration of these CR excipients in the formulation, the flow rate or the type of compression element used in the screws proved ineffective in controlling the problem. Rather, a re-design of the extruder screws was required to prevent generation of these extended-form granules.     

1-脱氧野尻霉素控释微丸的制备工艺优化及其药动学研究

1-脱氧野尻霉素控释微丸采用挤出滚圆和流化床方法进行制备。首先使用羟丙基甲基纤维素和微晶纤维素等辅料制备分散体、丸芯，再使用羟丙基甲基纳米纤维素邻苯二甲酸酯作为主要包衣材料进行包衣，并装入胶囊。采用SEM观察微丸的微观形态，以及测定其产率、脆碎度、密度、水分含量和粒径分布等物理性质，研究结果显示微丸性质符合中国药典标准规定。在体外释药试验中，溶出介质和放置方式对药物释放无显著影响，释放过程符合Baker-Lonsdale模型。对比研究1-脱氧野尻霉素原料药、分散体微丸和控释微丸在比格犬体内的控释特性，结果表明：与1-脱氧野尻霉素原料药相比，分散体微丸和控释微丸分别使1-脱氧野尻霉素的生物利用度提高了183.37%和243.87%。此外，1-脱氧野尻霉素控释微丸的体内-体外研究的相关性分析可知体外溶出和体内吸收之间呈现良好的线性关系。     

A new blend of polymeric encapsulation of azithromycin by spray-drying with a pH responsive in drug release

The microencapsulation of macrolides with polymers has been reported to retard the release of the drug in oral cavity. However, these methods are unable to control drug release in gastrointestinal tract. The aim of the present study was to investigate the effect of formulation of a new polymeric encapsulation of azithromycin which is suitable for both masking and sustained release usage. Eudragit E100 and polyethylene glycol (PEG) 4000 were chosen as the barrier coatings. The spray drying technique was used to obtain the microcapsules containing azithromycin. To obtain the initial results, the effects of several parameters were evaluated. A 3:2:1 ratio of E100:PEG 4000:azithromycin at pH 6 gave the best coating condition. Thermogravimetric analysis and IR analysis data confirmed the encapsulation of azithromycin inside polymers. The encapsulated drug was released in different rates from the particles by changing the pH (1.7 and 7.4). An analysis of the kinetic release properties indicates that the release of the drug is a combination of swelling and diffusion mechanism. The synergistic cooperation between polymers and drug due to the existence of several hydrogen bonding is supposed to influence the pH-responsive property of the encapsulated drug. Moreover, the use of mixtures of E100 and PEG 4000 appears to offer a good balance between cost and efficiency.     

An acryl resin-based swellable microneedles for controlled release intradermal delivery of granisetron

Swellable microneedles (SMNs) are made of hydrogels and can deliver drug with controlled delivery rate by the cross-link density of the hydrogel. In this study, an acryl resin-based SMNs was developed for poorly water-soluble drugs. The making process of the SMNs is very simple and only need 60?min. The SMNs has high mechanical strength and is not easily broken. In-vitro release of SMNs-loaded model drug, granisetron base (GRB), was investigated. The results showed that seven days controlled release of GRB was obtained when SMNs contained pore-foaming agents (1.5% dicalcium phosphate (CaHPO₄) and 1.5% polyvinylpyrrolidone (PVP)). The maximum amount delivered into skin was 86.158?±?7.82% of the initial GRB (2.1?mg) loaded on SMNs preparation. Pharmacokinetics study in rats indicated a dose-dependent profile of plasma GRB concentrations and that the controlled release of 2.1?mg dose was observed for 144?hours. In conclusion, these SMNs provided a potential minimally invasive route for controlled-release systemic delivery of poorly water-soluble drugs.     

肥料养分控释的技术、机理和质量评价

本文从肥料养分释放与作物吸收的"供—求"平衡关系出发,阐述了养分控释的重要意义;列举了养分控释的主要技术途径及其作用机理,并从控释材料来源、设备选型、控释效果等方面对各种技术途径进行了评述;在控释肥质量评价方面,说明了引入土壤因子的重要性,认为把"肥—土"作为一个整体来考虑,有利于更客观、更合理地评价控释肥的质量。     

膜控释盐酸二甲双胍缓释片的研制

制备膜控释盐酸二甲双胍缓释片并对其体外释放度的相关影响因素进行研究。以释放度作为判断原则,采用薄膜包衣法,通过正交试验确定最佳处方和工艺,制得盐酸二甲双胍缓释片,并对溶出方法、转速和溶出介质等因素进行考察,确定了制备盐酸二甲双胍包衣片的最佳处方和工艺。本制剂工艺简单,所用各种辅料成本低,制得盐酸二甲双胍包衣片释放度符合规定。     

砂姜黑土区控释尿素与普通尿素掺混对小麦-玉米轮作定位产量及氮肥利用率的影响

在驻马店新坡村进行了小麦-玉米轮作制下的控释尿素与普通尿素掺混比例定位试验研究。结果表明:控释尿素与普通尿素掺混处理的小麦、玉米产量均以70%控释尿素+30%普通尿素处理最好,第1年和第2年的小麦产量分别比100%普通尿素处理增产17.0%和21.1%,玉米产量分别比普通尿素处理增产16.2%和16.2%;氮肥利用率与产量结果一致,均以70%控释尿素+30%普通尿素处理最高,分别为53.9%和54.5%。     

不同处理方法对包膜控释氮肥中氮含量检测结果的影响

针对因包膜控释氮肥样品的粒径不同而造成氮含量测定值不稳定、不准确的问题,选取同一条生产线上的5个样品作为重复,并通过缩分器直接缩分法、根据各粒径质量比缩分混合法和根据粒径不同缩分单测法3种分样方法制备粉碎样,再采用滴定法测定氮含量。通过对测定结果的分析和比较可得出:粒径在3.35~4.75 mm范围内的样品质量分数占82.32%左右,且按照根据粒径不同缩分单测分样方法处理的样品所测得的氮含量值误差最小。