载葛根素的海藻酸镁胃内滞留释药系统的研究

采用滴制法制备微丸,选取海藻酸钠为载体材料,氯化镁为交联剂,碳酸氢钠为制泡剂,海藻酸钠与镁离子发生交联反应制得胃漂浮微丸,考察微丸的外观、粒径、微观结构、漂浮性以及释药行为。为延长药物在胃靶向长时间的释放,在单因素实验的基础上,以Eudragit L100和Eudragit RSALO作为载体材料制备载药固体分散体,粉碎过筛后加入海藻酸钠溶液中,依法制备载药固体分散体胃漂浮微丸,以Eudragit L100、Eudragit RSALO和药物的质量比为考察因素,评价其漂浮性和释放度。结果表明制得的载药固体分散体胃漂浮微丸持续9 h有超过95%的漂浮率,载药固体分散体微丸累积释放在5 h达到76% ~ 83%。本文制备的载药固体分散体胃漂浮微丸可在模拟胃液中持续漂浮并缓慢释放药物,为这类药物的胃漂浮给药系统的发展提供了思路。     

氨茶碱多剂量型胃漂浮颗粒的制备及影响因素

作者制备了氨茶碱的多剂量型胃漂浮颗粒，并考察了影响其漂浮性能和释药速度的各种因素。结果表明，增加十六醇和十八醇用量可以增加颗粒的漂浮力；增加乙基纤维素溶液浓度，减少甲基纤维素用量或增大颗粒的粒度，可以延缓药物从制剂中的释放速度。     

胃滞留给药系统的研究开发进展

胃滞留型缓释给药系统可增加"窄吸收窗"药物的滞留时间、提高其生物利用度、增加患者顺应性等优点。近二三十年来各国学者对该类新型制剂开展了大量研究,取得不少进展。本文拟对漂浮型、黏附型以及膨胀型三种胃滞留缓释给药系统的设计思路、辅料应用、体内外释放行为等进行简要的介绍和评价,为胃滞留型缓释给药系统的研究开发提供科学依据。     

多单元双嘧达莫胃漂浮缓释制剂的制备及其处方优化

目的制备多单元胃漂浮制剂双嘧达莫胃漂浮缓释微丸,并考察其体外漂浮和释放性质。方法采用挤出滚圆法制备轻质含药丸芯,底喷流化床包衣技术将乙基纤维素(EC)喷于含药丸芯表面形成缓释膜材,控制微丸的漂浮性和药物的释放特性;采用正交试验设计对包衣微丸的处方进行优化和筛选,并对最佳处方进行验证试验及释放模型拟合。结果包衣液中致孔剂含量质量分数为20%、增塑剂含量质量分数为5%、包衣质量分数增加为4%时,所得微丸的体外漂浮性和缓释释放度均达到了要求。12 h微丸的漂浮率大于90%,8 h累计释放量达到85%以上,包衣微丸的释药符合一级释药模型。结论自制产品质量稳定,工艺简单可靠,所得的胃漂浮缓释微丸达到了缓释与漂浮的双重要求。     

微片的特点和研究进展

在口服缓控释给药系统中,与单元型制剂相比,多单元型制剂的药物高度分散在胃肠道内,可以减少药物突释、提高用药安全性,还可以准确控制剂量、提高患者顺应性。多单元型给药系统包括颗粒、微球、微丸和微片等。该文主要介绍微片的特点和近年来的一些研究进展。     

一种新剂型——脉冲塞囊(Pulsincap)

Scherer DDS Ltd制药公司开发了一种新剂型即脉冲药物传递系统——脉冲塞囊。脉冲给药对于特定路线的配方具有许多优点。脉冲塞囊口服后可以在特定时间内释放药物,禁食者服药后约5小时,脉冲释放的药物就被结肠吸收一个剂量。脉冲给药起初不受新陈代谢和胃刺激的影响,药物可以稳定地输送到胃肠道较下部。该系统也可以在     

双嘧达莫胃漂浮缓释微丸的研究

目的结合固体分散技术制备双嘧达莫的褐藻酸钙-壳聚糖胃漂浮型缓释微丸(Dip-Ca-alg-cs-beads),对其漂浮性能,包封率,体外释药性能进行考察。方法以乙基纤维素,聚丙烯酸树脂II和Eudragit RLPO为联合载体制备双嘧达莫固体分散体,粉碎后分散于添加制泡剂的褐藻酸钠溶液中,并缓慢滴入添加醋酸的壳聚糖-氯化钙溶液中反应固化,干燥后得到胃漂浮缓释微丸。考察固体分散体对微丸体外释药的影响。结果通过调节配方,微丸在人工胃液中12 h漂浮率大于90%。双嘧达莫6 h释放65%~70%,包封率85%~90%。结论运用固体分散技术可实现双嘧达莫在褐藻酸钙-壳聚糖胃漂浮微丸(Ca-alg-cs-beads)中的缓释,并为这类药物的多单元胃漂浮给药系统的发展提供了思路。     

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。     

载药中空微球研究进展

目的介绍载药中空微球的研究进展。方法对中空微球的制备方法以及体内外漂浮性能的评价方法进行综述。结果该剂型可以延长药物在胃内的滞留时间,提高生物利用度并减少给药次数。结论中空微球是具有开发潜力的漂浮系统,具有广阔的发展前景。     

胃滞留给药系统的研究进展及其在中药制剂中的应用

在口服制剂中，胃滞留给药系统可以延长药物在胃内的滞留时间，进而延长其在整个胃肠道的转运时间，增加药物的吸收，从而提高临床疗效，因此它是一种理想的给药系统。本文通过查阅国内外文献进行归纳，从胃滞留给药系统的影响因素、分类、制剂研究（包括中药胃滞留制剂）及上市产品进展等方面对近年来胃滞留制剂的研究进展进行综述。     

Gastroretentive floating drug-delivery systems: a critical review

The oral delivery of drugs with a narrow absorption window in the gastrointestinal tract (GIT) is often limited by poor bioavailability with conventional dosage forms due to incomplete drug release and short residence time at the site of absorption. To overcome this drawback and to maximize the oral absorption of these drugs, gastroretentive systems such as mucoadhesive, high-density, expandable, and floating systems have been developed. These systems provide controlled delivery of drugs with prolonged gastric residence time. However, in humans, differences in various physiological and biological factors can affect the gastric residence time and drug-delivery behavior from gastroretentive systems. Some floating drug-delivery systems (FDDS) have shown the capability to accommodate these variations without affecting drug release. This review mainly focuses on various physiological considerations for development of FDDS, and highlights recent technological developments including new dosage forms and their production techniques (e.g., holt-melt extrusion, melt pelletization, and pulsed plasma-irradiation processes). Alternatives to the existing in vitro compendial methods for evaluating floating dosage forms will be discussed, and a critical analysis of the existing literature on FDDS, identifying the potential areas for future research, is provided.     

Release of furosemide from multiple-unit and single-unit preparations containing different viscosity grades of sodium alginate

The release characteristics and the effect of viscosity of sodium alginate on the release rate of furosemide (a rather poorly soluble drug) from hard gelatin capsules (single-unit), and minitablets (multiple-unit) filled in hard gelatin capsules, were evaluated. Swelling and erosion experiments showed a different behavior for each viscosity grade. Polymer characteristics influenced significantly the release of the drug from the preparations prepared and tested. The results indicate that erosion plays a significant role, accelerates release rate and shortens duration of drug release. Low viscosity formulations exhibited a greater erosion, and drug release was completed in 4 hours. Medium viscosity formulations showed intermediate erosion, while high viscosity formulations exhibited less erosion, and drug release was completed in 8 hours. The minitablets always displayed lower release and dissolution efficiency values than the capsules, and as the viscosity increased, the difference of dissolution efficiency between the two formulations increased accordingly. The results further indicated that the multiple-unit system demonstrated a more pronounced sustained effect than the single-unit, and therefore, it is a more suitable preparation for sustained release delivery of poorly soluble drugs. Analysis of release data indicate a rather zero-order release mechanism, which may be attributed mainly to swelling and an erosion/dissolution process.     

Gastroretentive dosage forms: a review with special emphasis on floating drug delivery systems

In the present era, gastroretentive dosage forms (GRDF) receive great attention because they can improve the performance of controlled release systems. An optimum GRDF system can be defined as a system which retains in the stomach for a sufficient time interval against all the physiological barriers, releases active moiety in a controlled manner, and finally is easily metabolized in the body. Physiological barriers like gastric motility and gastric retention time (GRT) act as obstacles in developing an efficient GRDF. Gastroretention can be achieved by developing different systems like high density systems, floating drug delivery systems (FDDS), mucoadhesive systems, expandable systems, superporous systems, and magnetic systems. All these systems have their own merits and demerits. This review focused on the various aspects useful in development of GRDF including the current trends and advancements.     

Release of Furosemide from Multiple-Unit and Single-Unit Preparations Containing Different Viscosity Grades of Sodium Alginate

The release characteristics and the effect of viscosity of sodium alginate on the release rate of furosemide (a rather poorly soluble drug) from hard gelatin capsules (single-unit), and minitablets (multiple-unit) filled in hard gelatin capsules, were evaluated. Swelling and erosion experiments showed a different behavior for each viscosity grade. Polymer characteristics influenced significantly the release of the drug from the preparations prepared and tested. The results indicate that erosion plays a significant role, accelerates release rate and shortens duration of drug release. Low viscosity formulations exhibited a greater erosion, and drug release was completed in 4 hours. Medium viscosity formulations showed intermediate erosion, while hh viscosity formulations exhibited less erosion, and drug release was completed in 8 hours. The minitablets always displayed lower release and dissolution efficiency values than the capsules, and as the viscosity increased, the difference of dissolution efficiency between the two formulations increased accordingly. The results further indicated that the multiple-unit system demonstrated a more pronounced sustained effect than the single-unit, and therefore, it is a more suitable preparation for sustained release delivery of poorly soluble drugs. Analysis of release data indicate a rather zero–order release mechanism, which may be attributed mainly to swelling and an erosion/dissolution process.     

Correlation of Phenylpropanolamine Bioavailability with Gastrointestinal Transit by Scintigraphic Monitoring of 111In-Labeled Hydroxypropylmethylcellulose Matrices

Two controlled-release hydroxypropylmethylcellulose (HPMC) matrix formulations, a single-unit and a multiple-unit system, have been evaluated in human volunteers. Both formulations contained the sympathomimetic drug phenylpropanolamine hydrochloride and each was radiolabeled with ¹¹¹Inbound Amberlite IR 120 ion-exchange resin. The formulations were administered to each of six healthy male volunteers and gastrointestinal (GI) transit was monitored using a gamma camera. Serum samples were taken at set time intervals and assayed for phenylpropanolamine content, thus allowing blood drug levels to be correlated with the position of the dosage form in the GI tract. The multiple-unit system emptied from the stomach gradually over a period of about 180 min, when administered after a light breakfast, whereas the single-unit dosage forms had extremely variable gastric emptying times (range, 60 to >570 min). However, both formulations provided prolonged phenylpropanolamine blood levels. The differences in the blood profiles obtained with the two formulations were attributed to variations in their in vitro release rates and not to any differences in their GI transit times.     

Coating of multiparticulates for sustained release

Multiparticulates are discrete particles that make up a multiple-unit system. They provide many advantages over single-unit systems because of their small size. Studies have shown that multiparticulates are less dependent on gastric emptying, resulting in less inter- and intra-subject variability in gastrointestinal transit time. They are also better distributed and less likely to cause local irritation. The drug dose in a multiple-unit system is divided over the multiparticulates that make up that system. As such, failure of a few units may not be as consequential as failure of a single-unit system. Multiparticulates may be prepared by several methods. Different methods require different processing conditions and produce multiparticulates of distinct qualities. Some of these methods may be broadly classified as pelletization, granulation, spray drying, and spray congealing. Drug particles may be entrapped within the multiparticulates or layered around them. Subsequently, these multiparticulates may be modified in many ways to achieve the desired drug-release profile. One approach to the modification of drug-release profiles in multiparticulates is to coat them. Reasons for the application of coating onto multiparticulates are to obtain functional coats, provide chemical stability, improve physical characteristics, and enhance patient acceptance. Coats are formed from various polymeric coating materials broadly classified as aqueous polymer dispersions, polymer solutions, molten polymers, and dry powders. Depending on the type of coating material used, functions such as sustained release (SR), targeted release, delayed release, and pulsatile release can be achieved. The focus of this review is on SR coating. The most common method used for the application of coating onto multiparticulates is air suspension coating. Other methods include compression coating, solvent evaporation, coacervation, and interfacial complexation. It is also possible to form coated microparticles by spray drying and spray congealing. A major part of this review is focused on factors affecting the coating of multiparticulates and drug-release characteristics from SR coated multiparticulates. Knowledge of these factors is important in the development of SR coated multiparticulates because control of these factors ensures consistency of drug release between batches of multiparticulates. These factors may be classified into four groups: characteristics of cores, characteristics of SR coats, coating equipment, and coating process conditions.     

Floating drug delivery systems for prolonging gastric residence time: a review

Oral delivery of the drug is the most preferable route of drug delivery due to the ease of administration, patient compliance and flexibility in the formulations. Recent technological advancements have been made in controlled oral drug delivery systems by overcoming physiological difficulties, such as short gastric residence time and highly variable gastric emptying time. Gastroretentive dosage forms have been designed over the past three decades to overcome these difficulties. Several technical approaches are currently utilized in the prolongation of gastric residence time, including highdensity, swelling and expanding, polymeric mucoadhesive, ion-exchange, raft forming, magnetic and floating drug delivery systems (FDDS), as well as other delayed gastric emptying devices. In this review, the current technological developments of FDDS including patented delivery systems and marketed products, and their advantages and future potential for oral controlled drug delivery are discussed.     

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.     

Pharmacokinetic study of repaglinide floating drug delivery system in rabbits by RP-HPLC method

The present work is aimed to study the pharmacokinetic parameters of optimized repaglinide floating drug delivery system(FDDS) by 24 factorial designs,followed by comparison with a commercially available formulation.The main effects and interactions of formulation variables were studied by using normal and pareto charts.The optimized formulation shows a fickian diffusion drug release mechanism.Pharmacokinetic parameters of the designed drug delivery system were evaluated in rabbit models.Mean while a simple,specific high performance liquid chromatographic method was developed and validated as per biopharmaceutical specifications,the linearity was observed at the range of 110-550 ng/mL(r2 = 0.999).By using methanol-phosphate buffer(pH 2.5)(70:30,v/v) as mobile phase at the flow rate of 1.0 mL/min the validation shows a better retention time of 5.2 min for repaglinide.And the same validation method was used for pharmacokinetic profile analysis of repaglinide marketed products and FDDS.The comparative pharmacokinetic results such as tmax,half-life,area under the curve,mean residence times were increased significantly for the repaglinide in FDDS than the marketed product of repaglinide except Cmax and elimination rate constant.     

A new multiple-unit oral floating dosage system. I: Preparation and in vitro evaluation of floating and sustained-release characteristics.

A multiple-unit type of oral floating dosage system, (a new type of floating pills which generate carbon dioxide gas) has been prepared in order to prolong the gastric emptying time (GET) of the preparation. The floating ability and the sustained-release characteristics of the system have been elucidated in vitro. The system was composed of sustained-release pills as seeds and double layers on the sustained-release pills. The inner layer was an effervescent layer containing both sodium bicarbonate and tartaric acid. The outer layer was a swellable membrane layer containing mainly polyvinyl acetate and purified shellac. When the system was immersed in water, it formed swollen pills, like balloons, with a density much lower than 1.0 g/mL. The reaction was due to carbon dioxide gas generated by neutralization in the effervescent layer with the diffusion of water through the swellable membrane layer. The system was floating completely within approximately 10 min and approximately 80% remained floating over a period of 5 h irrespective of pH and viscosity of the test medium. While the system was floating, a drug (p-aminobenzoic acid) was released. The release rate of the drug from the system was zero order and depended on the sustained-release characteristics of the sustained-release seeds composing the system. The release rate was not affected by the amount of the swellable membrane layer up to 13% (w/w).