Calendering as a direct shaping tool for the continuous production of fixed-dose combination products via co-extrusion

In this study calendering is used as a downstream technique to shape monolithic co-extruded fixed-dose combination products in a continuous way. Co-extrudates with a metoprolol tartrate-loaded sustained-release core and a hydrochlorothiazide-loaded immediate-release coat were produced and immediately shaped into a monolithic drug delivery system via calendering, using chilled rolls with tablet-shaped cavities. In vitro metoprolol tartrate release from the ethylcellulose core of the calendered tablets was prolonged in comparison with the sustained release of a multiparticulate dosage form, prepared manually by cutting co-extrudates into mini-matrices. Analysis of the dosage forms using X-ray micro-computed tomography only detected small differences between the pore structure of the core of the calendered tablet and the mini-matrices. Diffusion path length was shown to be the main mechanism behind the release kinetics. Terahertz pulsed imaging visualized that adhesion between the core and coat of the calendered tablet was not complete and a gradient in coat thickness (varying from 200 to 600 μm) was observed. Modulated differential scanning calorimetry and X-ray diffraction indicated that the solid-state properties of both drugs were not affected by the calendering procedure.     

复方丹参脉冲控释滴丸的制备及其体外释放度考察

目的 制备复方丹参脉冲控释滴丸,并考察其体外释放度.方法 以复方丹参滴丸为载药丸芯,对包衣材料配比及包衣材料用量进行选择,对控释滴丸体外释药情况进行考察.结果 溶胀层的种类与包衣增重、控释层的包衣增重对药物的释放影响显著,采用交联羧甲基纤维素钠（CMC-Na）作为溶胀层材料,乙基纤维素水分散体作为控释层材料,溶胀层包衣增重12％,控释层包衣增重20％,所制备的微丸时滞时间为4h左右,时滞后3h内累积释药达到80％.结论 制备的复方丹参脉冲控释滴丸体外释放可达到脉冲控释效果.     

Tensile Properties of Free Films Cast from Aqueous Ethylcellulose Dispersions

Free films of two commercially available formulations of aqueous ethylcellulose dispersion differing only in plasticizer content (Surelease/E-7-7050 without silica and E-7-7060 containing dibutyl sebacate and glyceryl tricaprylate/caprate as plasticizers, respectively) were cast and coalesced at temperatures ranging between 30 and 70°C. Mechanical properties of these films were measured using tensile stress analysis. Three mechanical parameters, namely, tensile strength, work of failure, and elastic modulus, were computed from the load-time profiles of these films. The results showed that the tensile strength and elastic modulus values of the films cast from both formulations increased with the corresponding increase in coalescence temperature up to 60°C, beyond which no significant differences were observed. In the case of work of failure, however, the difference between the two formulations was observed above 60°C. The films cast from Surelease/E-7-7050 formulation without silica (dibutyl sebacate as the plasticizer) were relatively softer than those from Surelease/E-7-7060 formulation (glyceryl tricaprylate/caprate as the plasticizer). At coalescence temperatures above 50°C, the films cast from both formulations exhibited temperature-dependent plastic deformation.     

肺癌治疗缓释化疗药栓塞装置的研究

目的研制用于肺癌治疗的带缓释化疗药栓塞装置,通过体外、体内的释放实验评价其释放特性。方法用乙基纤维素、顺铂配成一定的比例,在带Ivalon泡沫海棉的镍-钛记忆合金支架上分次涂层自制栓塞装置,其中5个采用转篮法体外药物释放实验,了解其体外释放特性。采用萨能奶山羊(n=6),经介入方法把本装置置入于右下肺动脉,对照组(n=6)采用右下肺动脉灌注顺铂,两组术后均定时抽右下肺静脉血测顺铂浓度,明确其体内释放特性。结果体外释放观察时间为24 h,体外累计释放率>70%,在最初1 h内有突释效应。带药栓塞组1、2、8 h测得的肺静脉血药浓度均高于灌注组(P<0.05)。结论采用乙基纤维素作为缓释材料制作的带缓释顺铂栓塞装置在体外、动物体内均具有缓释作用,在体内有利于提高肺组织局部药物的浓度。     

双氯芬酸钠脉冲控释微丸的制备与体外释放影响因素的研究

 目的制备双氯芬酸钠脉冲控释微丸并考察体外释放影响因素。方法采用挤出滚圆法制备载药丸芯，以水溶胀性材料低取代羟丙基纤维素为内包衣溶胀层，乙基纤维素水分散体为外包衣作为控释层制备脉冲控释微丸，并考察溶胀层材料类型、溶胀层和控释层包衣增重、介质pH值和微丸粒径等对药物释放的影响。结果药物通过控释层衣膜破裂释放，溶胀层材料类型、溶胀层和控释层包衣增重和微丸粒径等对脉冲控释微丸的释药时滞和释放速率均具有显著影响，药物释放情况不受介质pH值的影响。结论采用水溶胀性材料低取代羟丙基纤维素为内包衣层，制备的脉冲控释微丸，当内包衣层增重为11%和外包衣层增重胀层为17%时，达到了时滞为4h，时滞后1.5h累积释药80%以上的脉冲释药效果。     

乙基纤维素作为包衣材料在缓释盐酸苯丙醇胺树脂上的应用

 目的：考察影响药树脂体外溶出的因素，制备缓释盐酸苯丙醇胺(PPA·HCl)树脂。方法：以不同粘度规格的乙基纤维素(EC)为包衣膜材料制备缓释PPA·HCl树脂，以体外溶出试验，考察了树脂粒径、EC粘度、EC包衣增重百分率、EC分散介质(水或乙醇)以及体外释放介质的pH值和离子强度对上述缓释药树脂体外溶出的影响。结果：上述因素对药树脂的释药均有不同程度的影响，以EC 200 Pa·s包衣增重达150 g·kg^-1时，包衣药树脂在0.1 mol·L^-1HCl中的释放符合美国药典23版缓释PPA·HCl胶囊的要求。结论：用乙基纤维素为包衣膜材料，可以制备缓释PPA·HCl树脂。     

胸腺肽乙基纤维素微囊的制备和体外释药研究

 目的为提高胸腺肽的生物利用度，增强疗效，制备了胸腺肽乙基纤维素缓释微囊。方法用液中干燥法制备胸腺肽乙基纤维素微囊，正交设计法筛选其最佳制备工艺，Lowry法测定药物的含量，计算微囊的载药量、包封率及体外释药量。结果微囊粒径范围为30-80ym，平均粒径为52.64 tim，平均含药量为20.420h，平均包封率为81.64%，其体外释药符合Higuchi方程Q=5.15387+35. 350 59t1/2(r=0.997,n=9)，f1／2-80min，稳定性考察实验结果表明其稳定性较好。结论本法制备的胸腺肽乙基纤维素微囊粒径分布集中，体外释药有明显的缓释作用，具有良好应用前景。     

增塑剂及热处理对水性包衣美沙拉秦结肠靶向微丸体外释药 …

以乙基纤维素水分散体Ａｑｕａｃｏａｔ为包衣材料,制备延迟释药的美沙拉秦结肠靶向微丸,考察了４种塑塑剂（三乙酸甘油酯,癸二酯二丁酯、梅楷酸三乙酯、邻苯二甲酸二乙酯）和热处理时间对微丸释药的影响。结果显示,以枸楷酸三乙酯塑化微丸的释药最为理想,在延迟３～４ｈ后开始释药,１２内释药完全,于６０℃处理４ｈ后,释药即趋于稳定。     

乙基纤维素水性包衣技术I.水分散体与有机溶液包衣方法的比较

考察了乙基纤维素水分散体的基础性质,测定ＰＨ值、粘度、最低成膜温度、玻璃化转变温度,进行了处方相容性试验。以盐酸苯丙酸胺为模型工物,在流化床中蛊缓释微丸,考察在纤维素水分菜体的包衣应用特点,并与有机溶液包衣方法在缓释效果,增塑剂用量、包衣喷液方式的影响三方面进行比较。考察了水分菜体包衣微丸的稳定性,采用相似因子法评价微丸的体外释放度变化。