Preparation and evaluation of sustained-release diltiazem hydrochloride pellets

In this study,diltiazem hydrochloride(DTZ)pellets were prepared successfully by extrusionespheronization method.Then methacrylic acid and ethylcellulose coating formulations were employed to make the DTZ pellets sustained release.The pellets with different coatings were investigated by in vitro dissolution tests.At last,the pellets with the best coating copolymer were subjected to pharmacokinetic studies in beagle dogs.The dissolution profiles of pellets coated with Eudragit
NE30D were similar to Herbesser
,one of the marketed sustained release capsules.In the bioavailability study,the principal pharmacokinetic parameters of self-made pellets and the marketed ones were comparable;the relative bioavailability of DTZ sustained release capsules compared with Herbesser
was 98.5
36.4%.All the data indicated self-made sustained pellets could prolong the release of DTZ,decrease the fluctuation of drug level in vivo,and increase the compliance of patients.

Evaluation of Control Effects against Sugarcane Pests：A New Sustained-release and Long-lasting Pesticide and Convenient and Efficient Pesticide Application Technology

[Objective]The paper was to screen a new ideal sustained-release,long-lasting and low-toxic pesticide and convenient and efficient pesticide application technology for controlling Ceratovacuna lanigera and Baliathrips serratus. [Method]2% Imidacloprid GR were selected and applied in the soil for field efficacy trial. [Result] The optimum dosage of 2% imidacloprid GR was 30 kg/hm^2（ active ingredient 600 g）,which can be mixed with fertilizer（ 30 kg pesticide and 40-80 kg fertilizer per hm^2） once combined with sugarcane planting management or big ridging during February and June. The control effects against C. lanigera and B. serratus could be more than 98. 2% and 81. 1%,respectively. The actual yield and sugar content in various pesticide treatments were increased by 33 390 kg/hm^2 and 6. 6% respectively compared to blank control. [Conclusion]2% imidacloprid GR has good control effects on C. lanigera and B. serratus. It is a new pesticide with ideal sustained-release,long-lasting and low-toxin effects against C. lanigera and B. serratus. Therefore,it could be used alternatively with other pesticides,to delay production and development of drug resistance.

Implementation of a Simulation Model of the Controlled Release of Molecular Species from Halloysite Nanotubes

In this work a three-dimensional, time-quantified Monte Carlo model that efficiently describes diffusion through and from nanotubes is implemented. Controlled delivery from Halloysite Nano-tubes (HNT) is modeled based on interactions between the HNT’s inner wall and the nanoparticles (NPs) and among NPs themselves. The model was validated using published experimental data. The validated model is then used to study the effect of multiples parameter like HNT diameter and length, particle charge, and ambient temperature on the release of encapsulated NPs. The results show that release profiles depend on the size distribution of the HNT batch used for the experiment, as delivery is sensitive to HNT lumen and length. A very good agreement with the experiment is observed when a weighted average release profile is compared to the experimental profile. Although the NP dynamics is temperature-dependent, the effect is minimum within the range of temperatures relevant to biomedical applications, but will be relevant for other applications at temperatures significantly different from room temperature. This model can be used to predict the best conditions for a particular delivery need.

PEGylated PLGA Nanoparticles as Tumor Ecrosis Factor-α Receptor Blocking Peptide Carriers:Preparation,Characterization and Release in vitro

To assess the merits of PEGylated poly （lactic-co-glycolic acid） （PEG-PLGA） nanoparticles as drug carriers for tumor necrosis factor-α receptor blocking peptide （TNFR-BP）, PEG-PLGA copolymer, which could be used to prepare the stealth nanoparticles, was synthesized with methoxypolyethyleneglycol, DL-lactide and glycolide. The structure of PEG-PLGA was confirmed with ^1H-NMR and FT-IR spectroscopy, and the molecular weight （MW） was determined by gel permeation chromatography. Fluorescent FITC-TNFR- BP was chosen as model protein and encapsulated within PEG-PLGA nanoparticles using the double emulsion method. Atomic force microscopy and photon correlation spectroscopy were employed to characterize the stealth nanoparticles fabricated for morphology, size with polydispersity index and zeta potential. Encapsulation efficiency （EE） and the release of FITC-TNFR-BP in nanopartieles in vitro were measured by the fluorescence measurement. The stealth nanoparticles were found to have the mean diameter less than 270 nm and zeta potential less than -20 mV. In all nanoparticle formulations, more than 45% of EE were obtained. FITC-TNFR-BP release from the PEG-PLGA nanoparticles exhibited a biphasic pattern, initial burst release and consequently sustained release. The experimental results show that PEG-PLGA nanoparticles possess the potential to develop as drug carriers for controlled release applications of TNFR-BP.

Preparation and in vitro-in vivo evaluation of intestinal retention pellets of Berberine chloride to enhance hypoglycemic and lipid-lowing efficacy

Berberine chloride(BBR) is a pharmacokinetic profile of drug with poor bioavailability but good therapeutic efficacy,which is closely related to the discovery of BBR intestinal target.The major aim of this paper is to develop BBR intestinal retention type sustained-release pellets and evaluate their in vivo and in vitro behaviors base on the aspect of local action on intestinal tract. Here,wet milling technology is used to improve dissolution and dissolution rate of BBR by decreasing the particle size and increasing the wettability. The pellets are prepared by liquid layer deposition technology,and then the core pellets are coated with Eudragit~?L30 D-55 and Eudragit~?NE30 D aqueous dispersion. The prepared pellets show high drug loading capacity,and the drug loading up to 93%. Meanwhile,it possesses significant sustained drug release effect in purified water which is expected to improve the pharmacokinetic behavior of BBR. The pharmacokinetics results demonstrate that the halflife of BBR was increased significantly from 24 h to 36 h and the inter-and intra-subject variability are decreased compared to commercial BBR tablets. The retention test results indicate that the pellet size and Eudragit~?NE30 D plays an important role in retention time of the pellet,and it is found that the pellets with small particle size and high Eudragit~?NE30 D coating content can stay longer in the intestine than the pellets with large particle size. All in all,BBR intestinal retention type pellets are prepared successfully in this study,and the pellets show satisfactory in vivo and in vitro behaviors.

口服液体缓控释制剂技术的研究进展

目的针对各类口服液体缓控释技术的释药机理、应用特点及局限性进行综述,为此类制剂的开发提供参考。方法查阅国内外相关文献,对口服液体缓控释技术进行整理归纳。结果目前已有基于离子交换树脂和微囊技术的口服液体缓控释制剂上市,此外,微球、固体脂质纳米粒、原位凝胶等技术也应用于口服液体缓控释制剂领域。结论口服液体缓控释给药系统相比于传统固体缓控释制剂,因其口服可接受性良好,剂量调整灵活,给药依从性优势明显,具有良好的开发应用前景。

琥珀酸美托洛尔缓释微丸保护性衣层对其缓释片形成的影响与初步评价

目的评价羟丙纤维素及羟丙甲纤维素对琥珀酸美托洛尔缓释微丸的机械保护作用及差异。方法用不同分子量等级的羟丙纤维素和羟丙甲纤维素对琥珀酸美托洛尔缓释微丸进行包衣,通过检测微丸负压载荷、微丸完整性、体外溶出曲线,评价两种高分子材料对微丸的保护效果。通过制备了羟丙纤维素和羟丙甲纤维素薄膜并考察两种高分子材料薄膜的抗张强度、延展率、韧性和弹性模量等方面的机械性能差异。结果包被羟丙纤维素和羟丙甲纤维素的琥珀酸美托洛尔微丸,断裂载荷增加,压片后微丸完整性提高,机械性能提升,药物泄漏率降低。结论羟丙纤维素和羟丙甲纤维素保护层包衣对琥珀酸美托洛尔片释放单元有一定的机械保护作用,羟丙纤维素具有相对更高的保护能力,可以为多单元微丸药物释放系统的微丸保护策略提供借鉴。

外加电压对原位缓释碳源释碳效果影响的研究

为改善城市污水处理厂外加碳源成本高、产泥量大等问题,利用废弃纸屑与纤维素降解菌为原料制备投加型缓释碳源,并通过控制外加电压调控碳源释放速率。研究结果表明,在0.4 V的电压下,释碳微生物的响应效果最为显著。高通量测序结果显示,外加电压能够显著抑制产酸菌活性,而促进电活性菌丰度增加,证明外加电源的方法可通过调控功能微生物的群落结构及活性来控制碳源释放情况,可为进一步优化污水处理工艺自动化控制及碳源投加方式的选择提供理论依据与技术支撑。

甜橙香精微胶囊的制备及缓释性能研究

为了改善香精微胶囊的缓释性能、提高香精利用率,以甜橙香精为芯材、六亚甲基二异氰酸酯(HDI)三聚体为合成壁材的单体、聚乙二醇(PEG)和石墨烯(GR)作为温控材料,利用界面聚合法制备温控香精微胶囊(egHDI-O),考察芯壁比、剪切乳化机的转速、温控组分对甜橙香精微胶囊形貌、组成、芯材含量和缓释性能的影响。结果表明:在甜橙香精微胶囊芯壁比为1∶2,转速为8000 r/min,乳化剂为吐温80,PEG和GR用量分别为200 g/L和5 g/L工艺条件下制备的egHDI-O具有良好的形貌和均匀的粒径,其芯材含量(质量分数)可达74%;相比于未添加PEG和GR的微胶囊,egHDI-O具有优良的温控性能。研究为开发新型温控缓释赋香材料提供了新思路。

中药缓控释制剂研究进展

目的归纳中药缓控释制剂研究进展,为了解中药缓控释制剂制备工艺、处方和质量评价提供参考。方法通过文献检索,对不同缓控释制剂新类型的优缺点,中药缓控释制剂制备工艺、质量评价体系进行分析。结果缓控释制剂新类型涉及固体脂质纳米粒缓控释制剂、口服渗透泵缓控释制剂、胃滞留给药缓控释制剂、生物黏附微球、固体分散体,制备工艺采用多种筛选方法得出最佳工艺,中药缓控释制剂的质量评价方法包括体外释放度研究、体内释药和体内外相关性研究等。结论中药缓控释制剂研究主要集中在中药单体成分、中药提取物或有效部位、中药多个单体成分组合开发的中药制剂,质量评价体系主要有体内释放度、体外释放度和体内外相关性研究,可为中药缓控释制剂发展提供参考。

盐酸伊伐布雷定缓释微丸的制备工艺及其药动学研究

目的制备盐酸伊伐布雷定缓释微丸,考察其载药率、体外释放度及其在大鼠体内的药动学特征。方法采用流化床包衣法制备盐酸伊伐布雷定缓释微丸,以载药率为评价指标,通过正交试验设计优化载药层工艺参数,以体外释放度为评价指标,通过响应面实验设计优化缓释层处方。健康雄性SD大鼠随机分成2组:盐酸伊伐布雷定缓释微丸组和盐酸伊伐布雷定片组,单次给药后,测定不同时间点的血药浓度,运用Das20软件计算药动学参数。结果载药层处方:盐酸伊伐布雷定原料药075 g、羟丙基甲基纤维素180 g、水40 g,流化床工艺参数:进风量13 m^(3)·h^(-1)、进风温度50℃、雾化压力12 bar、蠕动泵流速09 mL·min^(-1);缓释层处方:乙基纤维素78%、聚乙二醇400091%、柠檬酸三乙酯20%。平均载药率924%,12 h累计释放度为9237%;盐酸伊伐布雷定缓释微丸较普通片剂的相对生物利用度为13559%。结论盐酸伊伐布雷定缓释微丸制备工艺重现性良好,体内外缓释效果明显,生物利用度显著提高,为盐酸伊伐布雷定缓释制剂的研究提供了基础。

CaO_(2)纳米粒子的制备及应用研究进展

CaO_(2)纳米粒子作为一种H_(2)O_(2)的替代品,制备较为简单,且应用广泛,在通过芬顿反应等机制治理环境污染方面扮演着重要的角色。但由于CaO_(2)与水反应产生H_(2)O_(2)和O_(2)的速率较快,通常需要在其表面包裹一层高分子材料,作为缓释剂。本文主要介绍了不同的制备CaO_(2)纳米粒子的方法以及过程中使用到的不同缓释剂,总结了CaO_(2)纳米粒子与细菌、Fe^(2+)、O_(3)等联用处理不同污染物(三氯乙烯、土霉素、芳烃污染物、重金属等)的应用进展。

盐酸二甲双胍缓释片联合饮食控制、运动疗法治疗社区2型糖尿病的效果分析

目的探讨盐酸二甲双胍缓释片联合饮食控制、运动疗法治疗社区2型糖尿病的效果。方法选取我院接收的426例2型糖尿病患者为对象,案例纳入时间为2022年3月至2023年3月,用随机数字表法分组,各213例,对照组开展常规盐酸二甲双胍缓释片治疗,观察组在对照组基础上联合饮食控制、运动疗法治疗。对比两组血糖指标、血脂指标及并发症发生情况。结果治疗后观察组患者空腹血糖、餐后2 h血糖及糖化血红蛋白指标均低于对照组(P<0.05);观察组患者低密度脂蛋白胆固醇、甘油三酯、总胆固醇指标均低于对照组(P<0.05);观察组患者神经病变等并发症发生率低于对照组(P<0.05)。结论对2型糖尿病患者积极实施盐酸二甲双胍缓释片联合饮食控制、运动疗法治疗,可有效提高临床控糖效果,降低患者血糖、血脂指标,减少相关并发症发生。

实蝇诱杀剂对梨园柑橘小实蝇的防治效果试验

为寻找适合灌阳的柑橘小实蝇绿色防控方法,减少化学农药用量,保障食品安全,2020年在灌阳县梨园中开展了新型缓释实蝇诱杀剂对柑橘小实蝇的田间防治试验。结果显示,新型缓释实蝇诱杀剂对柑橘小实蝇具有较好的防治效果,其中叶面点喷施相对防效达50.98%、树杆涂施相对防效为31.37%。另外,点喷叶处理用工为常规处理用工的1/10,涂杆处理用工为常规处理用工的1/30;点喷叶处理减少化学农药使用量达98.52%,涂杆处理减少化学农药使用量达99.59%。

多元定位释药技术制备舒胸缓释胶囊的研究

目的采用多元定位释药技术制备舒胸缓释胶囊。方法将处方药材精制后制备成舒胸微丸,然后分别采用HPM C、Eudrag it L 30D-55、Eudrag it L 100-Eudrag it S100混合物(1∶5)制备成3种包衣微丸,并按一定比例混合装入胶囊中。结果HPM C包衣微丸在任何pH值条件下均可释药,Eudrag it L 30D-55包衣微丸在pH≥5.5时开始释药,Eudrag it L 100-Eudrag it S100(1∶5)包衣微丸在pH≥6.8时开始释药。由3种包衣微丸混合制备而成的缓释胶囊,在模拟人体胃肠道pH变化条件下,呈现出一种pH依赖型梯度缓释特征,而且处方中的主要成分三七总皂苷、红花黄色素、阿魏酸、川芎嗪的释放度差异无显著性。结论采用定位释药技术制备而成的舒胸缓释胶囊中理化性质不同的各成分在缓释的同时可以达到同步释放,遵循了中药制剂复方配伍的整体观和用药思想。

灯盏花素缓释微丸制备工艺与处方优化的研究

目的 考察灯盏花素缓释微丸的制备工艺和最优处方 ,并对释药机制进行探讨。方法 利用挤出滚圆法制备骨架型微丸 ,采用单因素考察和正交设计筛选最优处方 ,通过方程拟合探讨释药机制。结果 所得微丸的制备工艺简单 ,微丸大小均匀 ,载药量大且药物含量均匀 ,能达到缓释 12 h的试验设计要求 ;释药机制以药物扩散为主 ,兼有骨架溶蚀。结论 利用挤出滚圆法制备灯盏花素缓释微丸方法简单 ,适于工业化生产。

双嘧达莫缓释微丸的研制及其体外释放特性

目的 :制备双嘧达莫 pH非依赖型缓释微丸 ,使药物释放不受胃肠道pH值变化及个体差异的影响。 方法 :采用固体分散技术 ,将药物与联合载体 (EudragitL、EC和PEG 60 0 0 )的混和有机液喷包于微晶纤维素 (MCC)空白丸芯上形成膜衣骨架型共沉淀物结构 ,以正交设计进行处方优化 ,考察不同pH条件下缓释微丸的释放特性。结果 :缓释微丸的体外药物释放呈pH非依赖型释放特征 ,符合一级动力学方程。结论 :具有溶解度pH依赖性的药物 ,以固体分散技术处理 ,通过不同性质载体的调节作用 ,可以制成pH非依赖型的缓释制剂。

左金胃漂浮缓释片中小檗碱、巴马汀、吴茱萸碱和吴茱萸次碱的体外释放规律和机制研究

目的探讨左金胃漂浮缓释片体外多成分释放的规律和机制。方法采用转篮法以人工胃液为介质,以HPLC法测定左金胃漂浮缓释片中小檗碱、巴马汀、吴茱萸碱和吴茱萸次碱在8 h内的体外累积释放率,通过相似因子比较法、Higuchi方程,零级、一级释放方程等释放模型拟合法以及Peppas方程研究左金胃漂浮缓释片多成分释放的规律。结果左金胃漂浮缓释片中4种生物碱的平均释放曲线相互之间的相似因子均大于80%,均以Higuchi释放模型为最佳拟合模型,释放机制均为扩散协同骨架溶蚀作用。结论左金胃漂浮缓释片中生物碱类成分的释放具有均衡缓释性。

麝香保心pH依赖型梯度释药微丸的研究

目的 制备麝香保心pH依赖型梯度释药微丸并进行体内外考察。方法 分别以HPMC ,EudragitL 30D 5 5和EudragitL10 0 EudragitS10 0 (1∶5 )为包衣材料制备pH依赖型梯度释药微丸 ,并进行体外释放度、胃肠道转运和体内药代动力学研究。结果 冰片和人参总皂苷体外释放度的f2 值为 79 6 ,3种包衣微丸分别在胃、十二指肠和空回肠部崩解 ,由 3种微丸组成的缓释胶囊中冰片的Tmax与原丸剂相近 ,而Cmax明显降低 ,相对生物利用度为 96 %。结论缓释胶囊中的冰片和人参总皂苷在体外可同步缓释 ,在体内具有pH依赖性崩解溶散的特征 ,冰片作为指标性成分具有梯度缓释的药代动力学特点。

双嘧达莫缓释微丸的药动学及相对生物利用度研究

目的 :以市售双嘧达莫普通片为参比制剂 ,评价自制双嘧达莫缓释微丸的相对生物利用度和生物等效性。方法 :采用随机交叉分组实验设计 ,给 4条Beagle犬分别给予单剂量 5 0mg的双嘧达莫缓释微丸和普通片 ,po ,按设计采集 12h内动态血标本 ;以经改进的HPLC法测定血浆药物浓度 ,以二室模型计算 2种制剂在动物体内的药动学参数和相对生物利用度。结果 :参比制剂和测试制剂的Tmax 分别为 (0 .92± 0 .0 9)h和 (1.5 7± 0 .12 )h ,Cmax分别为 (434.4± 36 .93)ng·mL- 1 和 (2 79.5 2± 2 4 .8)ng·mL- 1 ,AUC0～ 1 2 分别为 (92 2 .5 6± 5 2 .73)ng·h·mL- 1 和(115 2 .87± 5 5 .18)ng·h·mL- 1 ,t1 2 α分别为 (0 .6 9± 0 .0 5 )h和 (0 .89± 0 .12 )h ,t1 2 β分别为 (4.71± 0 .71)h和(17.6± 5 .5 3)h ,MRT分别为 (2 .91± 0 .14 )h和 (3.5 4± 0 .0 6 )h ,统计分析显示 ,各主要药动学参数均有显著性差异。双嘧达莫缓释微丸相对于普通片的平均生物利用度为 (12 5 .0 6± 4 .38) %。结论 :双嘧达莫缓释微丸具有明显的缓释特征 ,其生物利用度和药物吸收程度显著优于双嘧达莫普通片。