复方甲硝唑缓释栓的制备及体外释放度考察

目的:制备适合老年人用的复方甲硝唑缓释栓,并考察其体外释放度。方法:以甲硝唑和硝酸咪康唑为主药,羟丙基甲基纤维素为骨架材料,利用热熔法制备缓释栓剂;同时采用篮法,以0.5%十二烷基硫酸钠溶液为介质,硝酸咪康唑为对象,进行体外释放度评价。结果:所制制剂外观、性状良好,可持续12h释药,体外释放行为符合Higuchi方程。结论:该制剂制备工艺合理、简单易行,并具有良好的体外释药特性,符合缓释制剂的要求。     

克拉霉素缓释包衣微丸的制备及体外释放度研究

目的制备克拉霉素缓释包衣微丸,并对其体外释放度进行考察。方法采用挤出滚圆技术制备克拉霉素含药微丸。以优化的丙烯酸树脂类Eudragit NE30D和Eudragit L30D-55混和水分散体为包衣材料,采用流化床包衣技术,制备缓释包衣微丸。考察自制缓释微丸的体外释药速率,并与市售的克拉霉素缓释胶囊进行比较。结果通过释药行为的评价,得到优化的包衣处方为5∶1的Eudragit NE30D和Eudragit L30D-55混和包衣材料,其体外释放行为在不同的pH溶出介质中与市售制剂产品没有明显差异,体外释药过程符合一级释放模型。结论采用挤出滚圆和流化床技术,以及优化的Eudragit NE30D和Eudragit L30D-55混和水分散体包衣材料,成功制备了克拉霉素缓释包衣微丸。     

格列吡嗪缓释滴丸的制备及体外释放行为的考察

目的:制备格列吡嗪缓释滴丸并对其体外释放行为进行考察。方法:采用固体分散技术,以聚乙二醇类和硬脂醇为载体材料制得具有良好缓释效果的格列吡嗪缓释滴丸。通过线性和非线性最小二乘法回归,对零级、一级等体外释药模型进行评价。结果:将r2(确定系数)和AIC(Akaike’s informulation criteri-on)作为评价指标,自制缓释滴丸模型拟合结果以零级和Higuchi方程更优,16 h累积释放度达到95%以上。结论:自制缓释滴丸中药物实现近恒速释放,与市售制剂相比释药更完全,扩散为其主要释药机制。     

熔融高速搅拌法制备双氯芬酸钠缓释胶囊的研究

目的研究熔融高速搅拌法制备双氯芬酸钠缓释胶囊及其体外释药行为。方法采用KJZ-10型熔融高速搅拌制粒机制备含药微丸,以微丸体外释放度为指标,考察处方工艺因素对微丸体外释放度的影响,通过释放度曲线药动力学拟合确定微丸缓释机制。结果双氯芬酸钠微丸体外释放行为符合Higuchi方程Y=35.43t1/2-16.1523（r=0.9988）,释药机制主要是骨架溶蚀和扩散释放。结论该技术制备的双氯芬酸钠缓释微丸具有较好的释药性能及良好的缓释效果。     

盐酸美金刚缓释微丸的制备及体外释放度考察

目的:制备盐酸美金刚缓释微丸,并对其体外释放度进行考察。方法:采用流化床包衣法制备盐酸美金刚载药微丸,再用Eudragit RL 30D和Eudragit RS 30D进行包衣,制成盐酸美金刚缓释微丸,并考察盐酸美金刚缓释微丸的体外释药行为。结果:体外释放度试验显示,制备的盐酸美金刚缓释微丸在24 h内平稳释放且释药完全,释药规律符合零级释药模型。结论:用本方法制备的盐酸美金刚缓释微丸具有缓释效果。     

盐酸氯米帕明缓释片的制备及其体外释放度考察

目的:制备盐酸氯米帕明缓释片并考察其体外释放度。方法:以辅料羟丙基甲基纤维素(HPMC)、乳糖、可压性淀粉在处方中的含量为因素,体外释放度为指标,用正交试验优化处方并制备制剂,同时考察其体外释放度。结果:筛选最优处方为HPMC45mg、乳糖35mg、可压性淀粉40mg。所制制剂可持续24h释药,释药行为符合零级释放模型。结论:所制缓释片的处方合理,具有良好的缓释效果。     

熔融高速搅拌法制备双氯芬酸钠缓释胶囊的研究

目的 研究熔融高速搅拌法制备双氯芬酸钠缓释胶囊及其体外释药行为。方法 采用KJZ-10型熔融高速搅拌制粒机制备含药微丸,以微丸体外释放度为指标,考察处方工艺因素对微丸体外释放度的影响,通过释放度曲线药动力学拟合确定微丸缓释机制。结果 双氯芬酸钠微丸体外释放行为符合Higuchi方程 Y=35.43t_1/2-16.152 3(r=0.998 8),释药机制主要是骨架溶蚀和扩散释放。结论 该技术制备的双氯芬酸钠缓释微丸具有较好的释药性能及良好的缓释效果。     

布洛芬缓释滴丸的处方工艺优化及体外释药行为评价

目的:优化布洛芬缓释滴丸的处方工艺并评价其体外释药特征。方法:以硬脂酸为缓释基质、聚乙二醇6000为速释基质,采用熔融法制备布洛芬缓释滴丸。以圆整度、丸重差异、载药率、体外释药时间的综合评分为指标,以药物与基质质量比、药液温度、冷凝温度、滴距为因素,通过正交试验优化处方工艺并验证。在去离子水、盐酸溶液(pH 1.2)、磷酸盐缓冲液(pH 4.5、6.8)4种介质中,比较自制缓释滴丸与市售布洛芬缓释胶囊的体外释药行为,并对前者的释药行为进行拟合。结果:最优处方工艺为布洛芬-聚乙二醇6000-硬脂酸的质量比为4.0∶15.3∶0.7,药液温度为83℃,冷凝温度为8℃,滴距为11 cm;所制3批布洛芬缓释滴丸的丸重差异为2.067%、圆整度为96.73%、载药率为96.31%、12 h的累积释放度为93.05%,RSD分别为1.19%、0.28%、0.19%、0.81%。自制缓释滴丸与市售布洛芬缓释胶囊体外释药行为的相似因子f2均大于50,前者释药更符合Higuchi方程(r为0.988 1~0.997 2)。结论:成功优化布洛芬缓释滴丸的处方工艺,所制缓释滴丸的体外释药行为与市售布洛芬缓释胶囊相似。     

注射用蜂毒多肽温度敏感型缓释凝胶的制备及体外释放研究

目的制备注射用蜂毒多肽的温度敏感型缓释凝胶制剂并对其体外释药进行考察。方法以新型温度敏感聚丙交酯乙交酯聚乙二醇嵌段共聚物(PLGAPEGPLGA)为载体材料制备注射用蜂毒多肽缓释凝胶制剂,采用福林酚试剂法测定制剂在磷酸盐缓冲溶液中(pH7.4)的体外释放度,并对体外释放数据用KorsmeyerPeppas方程进行拟合。结果蜂毒多肽体外持续释放36d,其释药速率随聚合物的质量分数增加而降低,且聚合物分子结构中丙交酯比例增大对释药速率几乎没有影响。蜂毒多肽从凝胶中的释放初期以扩散为主,体外释放行为符合KorsmeyerPeppas方程,后期为凝胶溶蚀和药物扩散结合的作用机制。结论注射用蜂毒多肽的温度敏感型缓释凝胶制剂制备工艺简便,药物释放达到预期要求,同时说明温度敏感PLGAPEGPLGA嵌段共聚物作为注射用缓释给药系统的载体材料具有很好的应用前景。     

硫普罗宁缓释片的制备及体外释放度考察

目的制备硫普罗宁缓释片并对其体外释放度进行考察。方法以HPLC法为分析方法,采用相似因子法评价硫普罗宁缓释片体外释放行为。结果硫普罗宁缓释片的体外释放行为符合Highuchi方程。KollidonSR用量、填充剂的种类与用量及种类对药物的释放速度有较大影响,而硬度和释放介质的离子强度对药物的释放速度无显著影响。结论体外释放度符合缓释制剂要求,可进一步进行体内释药行为考察。     

喷雾干燥法制备丹酚酸壳聚糖微囊

目的以壳聚糖为载体制备丹酚酸微囊,并对其体外释药模式进行研究。方法以收率和载药量为指标,考察处方及工艺因素对微囊的影响,并对处方和工艺进行优化。结果壳聚糖质量浓度1.5%,丹酚酸与壳聚糖的质量比1∶3,进风温度190℃,蠕动泵速度300mL.h-1,所制得的微囊表面圆整,载药量为25.99%,收率为51.88%,包封率为86.21%,平均粒径为105.6nm。体外具有一定的缓释特性,在0～240min内拟合一级释药模型方程ln(1-Q)=-0.236 9 t+4.591 7,r=0.920 3。结论采用喷雾干燥法制得的丹酚酸微囊,收率和载药量较高,制备工艺简单,可望成为实现中药微球工业化的有效方法。     

Nevirapine nanosuspensions: stability, plasma compatibility and sterilization

The feasibility of preparing lyophilized or spray dried forms for reconstitution into nanosuspension (NS) was investigated in this study. The bare and surface modified aqueous NS of nevirapine were successfully converted into an anhydrous form by both techniques. The optimization of suitable cryoprotectant is essential to obtain completely dry product of desired properties. The NS adsorbed spray dried powder and granules would serve as excellent carriers for oral antiretroviral delivery. Furthermore, granules compressed to tablet showed sustained release compared to conventional marketed tablet. These results indicated that NS can be lyophilized and spray dried to prepare a product suitable for a parenteral and oral dosage form, respectively provided the formulation composition withstand phase changes during the drying processes process. Effect of sterilization method viz. steam and radiation on aqueous and lyophilized NS was also studied.     

Design and evaluation of sustained release microspheres of potassium chloride prepared by Eudragit.

The aim of the present work was to prepare and evaluate the sustained release of potassium chloride formulations. Eudragit RS and/or RL loaded with potassium chloride microspheres were prepared by a solvent evaporation method. The effect of sustained release of Eudragit microspheres was evaluated by an in vitro dissolution test and in vivo oral absorption study, and the results were compared to a commercial product (Slow-K). The results showed that Eudragit microspheres loaded with potassium chloride can be easily prepared and satisfactory results obtained considering the size distribution and shapes of microspheres by incorporating aluminum stearate. The encapsulation efficiency and loading capacity were about 84-90% and 27%, respectively. Moreover, the Eudragit RS (30-45 mesh) and Eudragit RS/RL (20-30 mesh) microspheres showed a similar sustained release effect of commercial product via in vitro dissolution and in vivo oral absorption study.     

Oral sustained delivery of paracetamol from in situ-gelling gellan and sodium alginate formulations

The purpose of this study was to evaluate the potential for the oral sustained delivery of paracetamol of two formulations with in situ gelling properties. Oral administration of aqueous solutions of either gellan gum (1.0%, w/v) or sodium alginate (1.5%, w/v) containing calcium ions in complexed form resulted in the formation of gel depots in rabbit and rat stomachs as a consequence of the release of the calcium ions in the acidic environment. In vitro studies demonstrated diffusion-controlled release of paracetamol from the gels over a period of 6h. The bioavailability of paracetamol from the gels formed in situ in the stomachs of rabbits following oral administration of the liquid formulations was similar to that of a commercially available suspension containing an identical dose of paracetamol.     

右旋酮洛芬缓释胶囊的制备及体外释药研究

目的:研究右旋酮洛芬缓释胶囊制备的处方条件。方法:采用喷雾干燥法制备右旋酮洛芬缓释细粒,填充入胶囊制成缓释胶囊,测定缓释胶囊(或细粒)的体外释放度,并考察制备处方条件对药物释放度的影响。结果:喷雾干燥法制备右旋酮洛芬缓释细粒,填充入胶囊即为缓释胶囊;在最优处方条件下缓释胶囊1h内体外累计释药量不超过30%,24h不低于90%。结论:该处方条件的右旋酮洛芬缓释胶囊的生产工艺简单可行,最终所得的缓释胶囊具有较好的缓释特征。     

吲哚美辛缓释胶囊与普通胶囊的生物利用度比较

本文比较了吲哚美辛(消炎痛)缓释胶囊和一种普通胶囊在体外的溶出速率以及在人体内生物利用度。吲哚美辛血清浓度用高效液相色谱(HPLC)测定。结果表明,2种胶囊制剂的溶出速率显著不同。在8名受试者中,2种胶囊的吸收程度基本一致;但缓释胶囊的峰药浓度(C_(max))显著低于普通胶囊(P<0.01),其达峰时间(T_(max))也明显延迟(P<0.01)。给予单剂量(50mg)缓释胶囊后,在给药后h4至h12,其血清浓度显著高于普通胶囊(P<0.05)。提示该缓释剂可避免普通制剂初期的高峰药浓度,可延长给药间隔时间。     

Preparation and evaluation of sustained release microspheres of potassium chloride prepared with ethylcellulose

The water-insoluble polymer ethylcellulose is used as a retardant to prepare the sustained release of potassium chloride microspheres by drying in a liquid process. The effect of sustained release of potassium from ethylcellulose microspheres was evaluated by the in vitro dissolution test, and was compared to a commercial product (Slow-K). The results showed that ethylcellulose microspheres loaded with potassium chloride could be easily prepared and satisfactory results could be obtained considering size distribution and shapes of microspheres by incorporating aluminum stearate. The encapsulation efficiency and loading capacity were about 84-93 and 36%, respectively. However, the potassium/ethylcellulose 2/2 (30-45 mesh) microspheres showed the similar sustained release effect of commercial product.     

喷雾干燥法制备对乙酰氨基酚缓释微球

目的 利用喷雾干燥法制备对乙酰氨基酚缓释微球,并考察其释放度.方法 以对乙酰氨基酚为模型药、乙基纤维素为载体材料、95 %乙醇为溶剂进行喷雾干燥而制备.结果 所制微球外观为圆整球形,粒度分布均匀,其体外释放度1 h时不少于15 %,2 h不超过40 %,12 h在90 %以上;在pH6.8的磷酸盐缓冲液中可缓慢并稳定地释放.经大鼠体内药物动力学研究表明,微球具有明显的缓释效果.结论 所制微球具有很好的缓释作用,操作方便,工艺稳定,有利于工业化生产.     

硫酸伪麻黄碱凝胶骨架型缓释片的制备与释放度试验

目的 研制硫酸伪麻黄碱缓释片并对其释放度的影响因素进行考察，方法 以羟丙甲纤维者（HPMC）为骨架材料制备硫酸伪麻黄碱凝胶骨架型缓释片，采用紫外分光光度法测定体外硫酸伪麻黄碱，并对缓释片进行释放度试验，结果 HPMC用量增加时释放速度变慢。磷酸氢钙用量增加时片削可压性得以改善．结论 该制刺缓释效果良好。     

Biopharmaceutical powders: particle formation and formulation considerations

It is well known that protein/peptide-based drug formulations are more stable in the solid state than in the liquid state, thereby offering stability advantages in ambient temperature storage, product shipping/distribution, and long-term shelf life. Novel powder-based drug delivery systems recently emerging for applications in sustained release, inhalation, intradermal delivery, etc, add more value to protein solid dosage forms. Despite great research interests in understanding the drying effects on protein stability and a large collection of publications focusing on this area, systematic accounts of powder formation techniques are lacking. This review is to summarize a number of methods currently available for protein powder preparation. Some are common methods such as lyophilization, spray drying, pulverization, and precipitation, and some methods are more recently developed such as supercritical fluid precipitation, spray-freeze drying, fluidized-bed spray coating and emulsion precipitation. In addition to examining the individual process effect on protein stability that is always the focus of formulation scientists, this review also likes to evaluate each method from a more practical sense in terms of process versatility and scalability. The conclusion is that each method has its own advantages and the use of a method is formulation and application specific. With the understanding of the principles and advantages of these methods, it can benefit our choice on selecting appropriate techniques for preparing a desired protein powder formulation for specific applications.