缓控释微丸制剂的研究进展

缓控释微丸制剂是一种多单元型给药系统，具有一单元型给药系统不可比拟的优点，成为目前缓控释制剂研究的热点。本文对缓控释微丸制剂包括骨架型微丸、膜控型微丸和骨架膜控两种技术结合制备的微丸的特点、所选用的材料及调节药物释放的方法等方面的研究进展进行了综述．并展望了微丸制剂的发展前景。     

多单元胃漂浮给药系统研究进展

胃漂浮给药系统可以增加药物在胃中的滞留时间，从而增加药物的吸收，提高药物的生物利用度。按药物剂量的分配方式，胃漂浮给药系统可分为“一单元”和“多单元”给药系统（如微丸、微球等）。“多单元”较“一单元”胃漂浮给药系统有着药物释放吸收的个体差异小、可避免药物剂量的“全或无”现象、对胃刺激性小、可以将不同释放速率的药物单元组合等优点。本文介绍了目前国内外多单元胃漂浮给药系统的类型、制备方法、释药情况及其体内漂浮性能的研究方法。     

缓控释微丸制备方法的研究进展

缓控释微丸制剂是一种多单元型给药系统,具有单一给药系统无法比拟的优点,成为目前缓控释制剂研究的热点。本文对缓控释微丸制剂的制备方法包括冻干制粒法,挤出滚圆法,离心造粒制丸法等方法的研究进展进行了综述,并对微丸制剂制备方法的未来前景进行展望。     

制备缓释微丸质量研究

缓释微丸作为缓控释药物制剂的一种形式,属于多单元型给药系统,具有一单元型给药系统不可比拟的优点,近年来随着现代制备工艺的逐渐成熟及辅料的发展,微丸已成为缓控释制剂发展的重要方向。本文以文献研究为基础,重点综述了骨架型微丸及膜控型微丸的特点以及质量研究进展,以期为微丸的进一步深入研究提供参考。     

微丸的研究进展

以微丸制剂为代表的多单元型给药系统因其特有的优越性,已成为缓控释制剂的主要发展方向。本文主要对微丸的形成机理、分类、制备工艺以及压片等相关方面作了较全面的介绍。     

药物制剂中薄膜包衣微丸的研究与应用

综述近年来薄膜包衣微丸在药物制剂中的研究与应用。微丸属于多单元型药物传递系统，具有众多优点。而将微丸制备技术和薄膜包衣技术相结合制成的具有特殊释药性质的薄膜包衣微丸，已经成为缓、控释制剂研究领域的热点。     

微丸压片技术的研究进展

口服缓、控释多单元制剂因其多方面的优点在药剂学领域中的应用日益广泛。其中,由微丸亚单元压制成的微丸型片兼有缓、控释和多单元制剂的优点。本文就近年来国内外微丸压片技术的研究进展进行综述,归纳和总结了微丸压片的机制、辅料和工艺参数对多单元微丸系统压片性能的影响,并展望了膜控微丸压片技术的发展前景。     

透皮吸收促进剂的临床应用

透皮吸收促进剂(简称穿透促进剂)系指可以加快药物穿透皮肤的速度而不对皮肤形成严重刺激和损害的物质。最早主要应用于软膏剂、擦剂、涂布剂等,随着制剂技术的不断发展、外用制剂的剂型不断增加,其用途不断扩大如骨架型透皮释放给药系统、压敏微储库型给药系统、贴布剂等。     

迷你片的研究与应用进展

迷你片（minitablet）又称微片,是指经特制的压片机模冲压制而成的直径介于2～3mm的微型片剂。它可以直接或者包衣后装入胶囊中,也可压制成大的片剂。迷你片是近年来医药领域发展的一种新型的单元给药缓控释制剂。迷你片制剂兼备微丸和片剂的优点。与片剂相比,迷你片属于多单元制剂,毒副作用减小,重复性好。与微丸相比,迷你片的制备工艺相对较为简单,剂量也更加精确。因此,迷你片近来越来越受到医药界的重视,其开发与应用前景十分看好。     

多单元调释给药系统在复方制剂中的应用

复方制剂由2种或2种以上的药物组分进行配伍,通过协同、加合作用或拮抗不良反应,与单方制剂比较,疗效更加显著。将多单元调释给药系统应用于复方制剂中,能更灵活地调节释药方案,全方位、多靶点、多环节作用,使药物生物利用度提高,不良反应降低。本研究针对镇痛、抗感染、降糖和降压几种常见复方制剂及中药复方制剂的复方原理作一综述,并重点阐述多单元调释给药系统在复方制剂中应用的优势,以期为复方制剂的临床开发提供新的思路。     

尼莫地平三次脉冲释药系统的研制

目的:制备尼莫地平三次脉冲释药系统并考察其体外释药性。方法:利用固体分散体技术制备尼莫地平的速释小片,采用干包衣法制备时滞4h和8h的脉冲小片,将此3种小片装入胶囊制成尼莫地平三次脉冲释药系统,并对小片和脉冲释药系统均进行体外释药研究。差示扫描量热(DSC)分析鉴别药物在固体分散体载体中的状态。结果:速释小片在30min内释药95%以上,脉冲小片在4h或8h的时滞期内释药<10%,时滞期过后的3h内释药完全;脉冲释药系统分别在5min、4h、8h时实现三次脉冲释药。药物均匀分散于载体中,并以无定型状态存在。结论:成功制备了尼莫地平三次脉冲释药系统。     

Compressed mini-tablets as a biphasic delivery system

Compressed mini-tablets systems are presented as a biphasic delivery system designed for zero-order sustained drug release. The outer layer that fills the void spaces between the mini-tablets was formulated to release the drug in a very short time (fast release), while the mini-tablets provided a prolonged release. Different composition (HPMC or EC) and number (10 or 21) of mini-tablets were used to obtain different drug release rates. The in vitro performance of these systems showed the desired biphasic behaviour: the drug contained in the fast releasing phase (powder enrobing the mini-tablets) dissolved within the first 2 min, whereas the drug contained in the mini-tablets was released at different rates, depending up on formulation. Based on the release kinetic parameters calculated, it can be concluded that mini-tablets containing HPMC were particularly suitable approaching to zero-order (constant) release over 8h time periods.     

Dissolution of theophylline from film-coated slow release mini-tablets in various dissolution media

The dissolution of an experimental formulation of film-coated slow release theophylline mini-tablets has been investigated using the USP paddle apparatus in test media at pH 1.2 (hydrochloric acid), pH 5.4 and 7.4 (phosphate buffers) at 37 degrees C. Monitoring of in-vitro theophylline release over 12 h, under identical hydrodynamic conditions, showed that the dissolution rate at pH 1.2 is substantially greater (95% of total drug content released in less than 10 h) than that in phosphate buffers. The maximum release after 12 h was approximately 20 and 30% of total drug content of the tablet at pH 5.4 and 7.4, respectively. However, in vivo bioavailability after oral administration of tablets to rabbits corresponded to over 95% of total drug, compared with the same dose administered intravenously. The retarded drug release during in-vitro dissolution in phosphate buffer was attributed to a possible interaction of phosphate ions with theophylline molecules at the tablet core-coat interface. These findings indicate that both rate and extent of theophylline release from the slow release coated mini-tablets are highly sensitive to phosphate buffers. The data also emphasize the usefulness of an animal model for assessment of in-vivo drug release and subsequent absorption, during the development of modified release dosage forms.     

盐酸伪麻黄碱脉冲小片包衣液处方优化

目的制备盐酸伪麻黄碱脉冲控释小片,并对其体外释药情况进行研究。方法制备盐酸伪麻黄碱含药片芯,采用丙烯酸树脂水分散体(Eudragit(RS 30D)制备盐酸伪麻黄碱脉冲控释小片。通过单因素实验考察药物释放的影响因素,确立处方组成,采用正交设计对包衣液处方进行优化。结果当隔离层增质量分数为2%、控释层增质量分数为5%、CMS-Na用量质量分数为25%,脉冲控释小片的时滞为6 h,体外具有脉冲释药特性。结论成功地制备了盐酸伪麻黄碱脉冲控释小片,体外释药符合脉冲释药的要求。     

Efficacy of gastro-retentive forms of ecabet sodium in the treatment of gastric ulcer in rats

The purpose of the present study is to investigate the influence of gastric retention of ecabet sodium (ECS) on its mucoprotective effect in rat ulcer models. Mini-tablets containing 9 mg ECS were prepared using the direct compression method. The release rates of ECS mini-tablets were controlled by the amount and viscosity grade of hydroxypropylmethyl cellulose incorporated. Gastric retention of ECS mini-tablets after oral administration to rats was visually confirmed using a fluorescence imaging system. Because ECS mini-tablets exhibited size-dependent gastric retention, their gastric retention time was prolonged as the release rate decreased. In the in vivo efficacy study, gastro-retentive dosage forms of ECS did not influence the mucoprotective effect in the immediate irritation model but enhanced the effect in the delayed irritation model compared with ECS suspension. This finding indicates that the duration of the mucoprotective effect of ECS can be extended by the employment of gastro-retentive dosage formulations and provides a rationale for development of ECS gastro-retentive dosage forms.     

Mini-tablets: a contemporary system for oral drug delivery in targeted patient groups

Introduction: Mini-tablets represent a new trend in solid dosage form design, with the main goal of overcoming some therapeutic obstacles such as impaired swallowing and polypharmacy therapy, and also offering some therapeutic benefits such as dose flexibility and combined release patterns. Mini-tablets are a promising patient-friendly drug delivery system.

Areas covered: Mini-tablets are tablets with a diameter ≤ 3 mm produced on conventional tablet presses equipped with multiple tooling. Mini-tablet production is similar to the production of standard tablets but requires excellent powder flow due to the small dies, exact control of process parameters and special caution during tablet press assembly in order to avoid tool damage. Mini-tablets (coated or uncoated and single- or multiple-unit systems) are mainly developed as patient-friendly systems for pediatric and geriatric patients and also for personalized medicine because they offer improved swallowing and flexible dosing, combining various release kinetics, doses and active compounds in only one system. Mini-tablets may also be successfully used as multiple-unit modified release systems (extended release, delayed-colon release, pulsatile and bi-modal release and gastroretentive systems) providing improved drug bioavailability compared with single-unit systems.

Expert opinion: Mini-tablets used as single- or multiple-unit oral dosage forms have enormous potential as a patient-friendly drug delivery system for targeted populations, providing improved swallowing, flexible dosing and a combination of different release patterns and/or different active compounds (decreasing dosing frequency and/or polypharmacy therapy problems). In terms of complete expression of the benefits of mini-tablets over other oral dosage forms on the market, further investigation in formulation possibilities and development of suitable dosing devices is of essential importance.     

In vivo evaluation of a theophylline oral controlled-release unit dosage form

A 200 mg controlled-release unit dosage form which was designed and developed showed desired in vitro release characteristics. This dosage form was subjected to in vivo studies (single and multiple p.o. dosing) in Beagle dogs with the aim of insuring the desired controlled-release performance in a biologic system. Using a parallel study design (intravenous, p.o. solution, p.o. controlled-release standard and p.o. controlled-release test dosage form), the dosage form index (DI), the fraction of drug absorbed (absolute bioavailability) (f) and the extent of (relative) bioavailability (EBA) of the experimental dosage form were determined.     

Formulation and development of gastroretentive drug delivery system for ofloxacin

The aim of the present study was to develop a delivery system wherein the retention of ofloxacin could be achieved for increased local action in gastric region against Helicobacter pylori infection. The formulation was optimized on the basis of in vitro buoyancy and in vitro release in citrate phosphate buffer (pH 3). The hydrodynamically balanced capsules were prepared by physical mixing of various grades of HPMC and poly(ethylene oxide) (PEO) alone as well as in combinations. Cellulose acetate pthalate, liquid paraffin, and ethyl cellulose were used as release modifiers so as to maintain release of drug over a period of 12 h. The capsules prepared with PEOWSR 60K and drug coated with 2.5% ethyl cellulose gave the best in vitro percentage release and were taken as the optimized formulations. Various grades of Eudragit and PEO were used in combination for formulating floating microspheres using solvent diffusion technique for preparation of multiple unit system. The use of two different solvents (dichloromethane and ethanol) that differed in the rate of diffusion led to formation of a hollow core in the microspheres, which was partially responsible for the flotation ability. The in vitro release of the floating capsules and microspheres was found to be 96.02% and 95.83% in 12 h, respectively. Both the dosage forms follow Higuchi model for release from formulations. By fitting the in vitro release data of single unit dosage form into zero-order, first-order, and Higuchi model, it could be concluded that the release followed Higuchi model, as the correlation coefficient (R2 value) was higher than those in the other two release models. In both cases of single and multiple unit dosage form, R2 values for Higuchi model were found to be good, showing that drug release followed non-Fickian diffusion mechanism.     

Matrix mini-tablets based on starch/microcrystalline wax mixtures

Matrix mini-tablets based on a combination of microcrystalline waxes and starch derivatives were prepared using ibuprofen as a model drug. The production of mini-tablets was preferred over the production of pellets, as up-scaling of the pelletisation process seemed problematic. Prior to tabletting, melt granulation in a hot stage screw extruder and milling were required. The in vitro drug release was varied using microcrystalline waxes with a different melting range, the slowest drug release being obtained with a formulation containing a microcrystalline wax with a melting range between 68 and 72 degrees C. Generally speaking increasing the wax concentration resulted in a slower drug release. In vitro drug release profiles were also modified using different starches and mixtures of starches. Increasing the ibuprofen concentration to 70% resulted in a faster drug release rate.     

脉冲释放制剂组合的数学解析

目的本研究采用数学手段对脉冲释放制剂的释药行为进行解析,根据两种制剂释药速率经时方程迭加的原理,构建组合系统的释药速率经时方程。方法按照最小偏差平方和SS原则,采用非线性最小二乘法模型嵌合通用程序,对组合系统进行模型嵌合,得到最适模型的释药速率经时方程,并据方程绘制释药速率经时曲线。结果以两种脉冲释放制剂的配比为1∶1的组合系统释药较平缓,而此时两次脉冲的释放速度比较接近。结论以短时缓释片芯为基础的脉冲组合型缓释制剂在改善不同组分释药同步性的同时,释药速率波动相对比较平缓。