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。     

盐酸雷尼替丁中空缓释微球的制备及其特性

目的:以盐酸雷尼替丁(RH)为模型药物,研究中空微球的制备,并对制备过程中的影响因素进行考察。方法:以乙基纤维素(EC)为载体材料,乙醇/乙醚为混合溶剂,采用溶剂扩散-挥发法制备盐酸雷尼替丁中空微球。以产率、平均粒径、载药量和微球形态为指标,考察了处方工艺对微球性能的影响。并考察了EC粘度,RH/EC比例以及粒径对微球释药速率的影响。结果:中空微球产率为84.51%,粒径分布均匀,平均粒径632μm,载药量13.71%,包封率55.86%。电镜扫描显示:微球外观圆整光滑,内部为中空结构。体外释药研究表明随着EC粘度的增加释药速率降低;随着RH/EC比例和搅拌速度的增加释药速率增加。最终所得到的中空微球缓释可达24h,体外漂浮实验表明在人工胃液中可持续漂浮48h以上。结论:该处方工艺简便可行,制得的盐酸雷尼替丁中空微球在人工胃液中缓释性和漂浮性良好。中空微球有望成为吸收窗药物的又一新型给药系统。     

双嘧达莫中空微球的制备及评价

目的制备双嘧达莫中空微球,并对其进行初步评价。方法采用溶剂扩散-挥发法制备双嘧达莫中空微球,以外观、平均粒径、载药量及包封率为指标进行单因素考察优化处方,并对优化处方制备的中空微球进行体外漂浮及体外释放实验。结果双嘧达莫中空微球的最优处方及工艺为:乙基纤维素质量浓度为100 g.L-1、乙基纤维素与药物的质量比为5:1、乙醇与乙醚的体积比为4:l、乳化剂质量浓度为10 g.L-1、硬脂酸镁质量浓度为0.2 g.L-1,反应温度为30℃,搅拌速度为300 r.min-1。以最优处方制备的双嘧达莫中空微球,其载药量为11.57%,包封率为70.12%。该微球在人工胃液中12 h漂浮率可达94%,在人工胃液中12 h释放达80%,且无突释现象。结论双嘧达莫中空微球具有较理想的体外漂浮及缓释特性。     

正交试验法优化西咪替丁中空微球的处方工艺及微球体外释药模式研究

目的优化西咪替丁中空微球的制备条件并对其释药模式进行研究。方法采用溶剂扩散-挥发法制备西咪替丁中空微球。以微球包封率、收率及漂浮率为指标,采用正交试验法优化处方工艺,最终得到分散性良好的微球。以优化处方制备的中空微球进行体外溶出实验,进行释放机理的探讨。结果采用正交试验法优化了西咪替丁中空微球的处方工艺,在最优处方下制得的微球外观圆整,微球的粒径较均匀,载药量与包封率分别为19.48%与65.37%,在人工胃液中12 h漂浮率可达99%。结论该方法制备工艺简单、重现性好,制得的中空微球在人工胃液中具有良好的漂浮及缓释特性,体外释药符合Higuchi模型。     

法莫替丁生物黏附型中空微球的制备与评价

目的制备法莫替丁生物黏附型中空微球,并对其进行初步评价。方法采用溶剂-扩散挥发法制备法莫替丁生物黏附型中空微球,以微球包封率、收率及漂浮率为指标通过正交试验优化处方工艺,以优化处方制备的微球进行离体黏附性试验、体外溶出实验,并进行释药机理的探讨。结果法莫替丁生物黏附型中空微球的最优处方及工艺为:乙基纤维素质量浓度为27.0 g·L-1,法莫替丁质量浓度为4.8 g·L-1,无水乙醇与无水乙醚体积比为17∶3。最优处方下制得微球外观圆整,粒径分布较均匀,在扫描电镜下横切面可见明显中空结构,平均包封率和离体黏附率分别为82.0%和98.0%,在人工胃液中12 h漂浮率可达87.0%。12 h体外释放90%以上。结论该法所制中空微球在人工胃液中具有良好的漂浮、黏附及缓释特性,体外释药符合Higuchi模型。     

微球给药系统及其质量评价

目的 为开展药物新剂型研究提供参考.方法 查阅相关专业文献,对微球给药系统的制备方法及质量评价进行综述.结果 微球给药系统的制备方法有溶剂挥发法、喷雾干燥法、乳化交联法.微球给药系统的质量评价包括形态及粒径分布、载药量及包封率、微球的释放速率、稳定性等.结论 微球给药系统作为一种新剂型,近年来受到广泛关注,具有广阔的发展前景.     

辅料对胃漂浮制剂漂浮性能的影响

胃漂浮制剂，是根据流体动力学平衡体系（HBS）原理设计，口服后长时间在胃内保持漂浮状态，能有效提高药物生物利用度的一种口服缓释制剂。随着药用辅料的发展和制剂技术的改进，胃漂浮制剂的剂型愈加丰富，有片剂、胶囊、微囊、微球、小丸等。胃漂浮制剂设计的关键是：其在胃内是否能达到预期的漂浮时间。通常胃漂浮制剂，     

淀粉微球给药系统

近年来,人们已注意应用水不溶性药物载体对人体特定器官给药。此种给药系统的剂型有脂肪乳剂、脂质体、红细胞影(无色红细胞)、渗透性聚合微囊以及固体微球,所有这些剂型均有各自的局限性。采用粒状微球可能是剂型开发中最有希望的给药系统之一。可溶性人血清白蛋白为血液中生理循环的药物载体,并可在体内降解,因而应用白蛋白微球载体特别受到重视。然而白蛋白微球可引起免疫反应。采用淀粉     

锐孔凝固浴法制备维生素B_2胃漂浮微球

目的用新方法制备维生素B2胃漂浮微球,并对其体外性质进行研究。方法用磁力搅拌器将聚合物溶液搅拌成均匀的泡沫,用锐孔凝固浴法制备微球,用紫外分光光度计测定其载药量、包封率和药物释放,并用自制仪器测定微球的漂浮力。结果微球能漂浮于模拟胃液12 h以上,具有良好的漂浮性能,药物释放可达到24 h,海藻酸钠(sodium alginate,Alg)和羟丙基甲基纤维素(hydroxypropyl methyl cellulose,HPMC)的质量对微球性质有较大影响。结论此方法制备的微球漂浮性能良好,并能缓慢释放药物,可以用做制备胃漂浮制剂。     

几种抗菌药物新剂型药代动力学研究概况

目的 :根据文献资料综述抗菌药物新剂型在细胞、组织的药物动力学特点。方法 :按抗菌药物的脂质体、纳米球、微球、微囊分别介绍。结果 :抗菌药物脂质体、纳米球、微球等可提高感染细胞或组织的药物浓度 ,同时具有缓释特性 ,延长有效药物浓度维持时间。结论 :新型给药系统具有靶向性 ,增强抗菌活性 ,降低毒性 ;一些抗菌药物适合制成脂质体、纳米球等新剂型     

Floating microspheres as drug delivery system: newer approaches

A controlled drug delivery system with prolonged residence time in the stomach can be of great practical importance for drugs with an absorption window in the upper small intestine. The main limitations are attributed to the inter- and intra-subject variability of gastro-intestinal (GI) transit time and the non-uniformity of drug absorption throughout the alimentary canal. Floating drug delivery systems (FDDSs) are expected to remain buoyant in a lasting way upon the gastric contents and consequently to enhance the bioavailability of drugs. The various buoyant preparations include hollow microspheres, granules, powders, tablets, capsules, pills and laminated films. Floating microspheres are specially gaining attention due to their wide applicability in the targeting of drugs to stomach. These floating microspheres have the advantage that they remain buoyant and distributed uniformly over the gastric fluid to avoid the vagaries of gastric emptying and release the drug for prolonged period of time. A major drawback of low-density floating drug delivery systems is that their performance is strongly dependent upon the gastric emptying process of stomach. Multiparticulate low-density particles can successfully prolong the gastric retention time of drugs. This article is a review of two important approaches utilized to prepare and improve the performance of floating microspheres.     

Microspheres as floating drug-delivery systems to increase gastric retention of drugs

Gastric emptying is a complex process, which is highly variable and makes in vivo performance of the drug-delivery systems uncertain. In order to avoid this variability, efforts have been made to increase the retention time of the drug-delivery systems for more than 12 h. The floating or hydrodynamically controlled drug-delivery systems are useful in such applications. The present review addresses briefly the physiology of the gastric emptying process with respect to floating drug-delivery systems. In recent years, the multiparticulate drug-delivery systems are used in the oral delivery of drugs. One of the approaches toward this goal is to develop the floating microspheres so as to increase the gastric retention time. Such systems have more advantages over the single-unit dosage forms. The development of floating microspheres involves different solvent evaporation techniques to create the hollow inner core. The present review addresses the preparation and characterization of the floating microspheres for the peroral route of administration of the drug.     

In vitro and in vivo evaluation of ranitidine hydrochloride loaded hollow microspheres in rabbits

The objective of this investigation was to develop the hollow microspheres as a new dosage form of floating drug delivery systems with prolonged stomach retention time. Hollow microspheres containing ranitidine hydrochloride (RH) were prepared by a novel solvent diffusion-evaporation method using ethyl cellulose (EC) dissolved in a mixture of ethanol and ether (6:1.0, v/v). The yield and drug loading amount of hollow microspheres were 83.21±0.28% and 20.71±0.32%, respectively. The in vitro release profiles showed that the drug release rate decreased with increasing viscosity of EC and the diameter of hollow microspheres, while increased with the increase of RH/EC weight ratio. Hollow microspheres could prolong drug release time (approximately 24 h) and float over the simulate gastric fluid for more than 24 h. Pharmacokinetic analysis showed that the bioavailability from RH-hollow microspheres alone was about 3.0-times that of common RH gelatin capsules, and it was about 2.8-times that of the solid microspheres. These results demonstrated that RH hollow microspheres were capable of sustained delivery of the drug for longer period with increased bioavailability.     

Preparation of Eudragit E100 microspheres by modified solvent evaporation method

The objective of this investigation was to develop the hollow microspheres as a new dosage form of floating drug delivery system with prolonged stomach retention time. Hollow microspheres containing ranitidine hydrochloride were prepared by solvent evaporation method using Eudragit RLPO dissolved in a mixture of dichloromethane and ethanol. The maximum yield and drug loading amount of hollow microspheres were 88.45% and 80 +/- 4.0%, respectively. The in vitro release profiles showed that the drug release rate decreased with increasing viscosity of Eudragit RLPO, while diameter of hollow microspheres increased with the increase of drug polymer weight ratio. Hollow microspheres could prolong drug release time (approximately 24 h) and float over stimulate gastric fluid for more than 12 h. These results demonstrated that ranitidine HCl hollow microspheres were capable of sustained delivery of the drug for longer period with increased bioavailability.     

Floating microspheres: to prolong the gastric retention time in stomach

A gastroretentive drug delivery system with prolong retention time in the stomach have great practical importance for drugs with an absorption window in the upper small intestine. Floating drug delivery system are expected to remain buoyant in the gastric content for prolong duration of time thus enhance the bioavailability of drugs. There are several gastroretentive drug delivery systems, which are floating microspheres, granules, tablets, powder, pills, laminated films and capsules. Floating microspheres are gaining special attention because of their wide applicability in the targeting of drug to stomach. Floating microspheres have several advantages, that they remain buoyant in the stomach and distributed uniformly to avoid the vagaries of gastric emptying and release the drug for prolong period of time.     

Floating dosage systems in drug delivery

The identification of new diseases and the resistance shown toward existing drugs calls for the introduction of new therapeutic molecules. In response, a large number of chemical entities have been introduced, of which some have absorption over the entire gastrointestinal tract (GIT), some have absorption windows (i.e., absorption sites, especially the upper part of the small intestine), and some have poor solubility in intestinal media altogether. The drugs belonging to the second and third categories, and the drugs required for local action in the stomach, require a specialized delivery system. All the above requirements can be met and effective delivery of the drugs to the absorption window, for local action and for treatment of gastric disorders such as gastro-esophageal reflux, can be achieved by floating dosage systems (FDS). To date, a number of FDS involving various technologies, carrying their own advantages and limitations, were developed, such as single- and multiple-unit hydrodynamically balanced systems (HBS), single- and multiple-unit gas-generating systems, hollow microspheres, and raft-forming systems. Various factors such as gastrointestinal physiology, dosage form characteristics, and patient-related factors control the behavior of FDS. This review discusses the anatomy and physiology of the stomach, the gastric emptying process, factors affecting the gastric retention of dosage forms, and various techniques adopted in the development of FDS.     

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.     

Floating-bioadhesive microspheres containing acetohydroxamic acid for clearance of Helicobacter pylori

A new strategy based on gastric retention is proposed for the treatment of Helicobacter pylori. (H. pylori) . A synergism between a floating and a bioadhesive system has been explored. Floating microspheres containing the antiurease drug acetohydroxamic acid (AHA) were prepared by a novel quasi-emulsion solvent diffusion method. The microballons were characterized for size distribution, morphology, drug content, drug release, and in vitro floating property. The microballons were coated with 2% w/v solution of polycarbophil by the air suspension coating method. The bioadhesive property of the microspheres was investigated by the detachment force measurement method. In vitro growth inhibition studies were performed in isolated H. pylori culture. The results suggest that AHA-loaded floating microspheres are superior as potent urease inhibitors whereas urease plays an important role in the colonization of H. pylori. We suggest that an oral dosage containing floating-bioadhesive microspheres may form a useful drug delivery system for the treatment of H. pylori.     

In vitro and in vivo evaluation of ranitidine hydrochloride ethyl cellulose floating microparticles

The real issue in the development of oral controlled release dosage forms is not just to prolong the delivery of drugs but also to prolong the presence of dosage forms in the stomach in order to improve the bioavailability of drugs with a 'narrow absorption window'. In the present study, an anti-ulcer drug, ranitidine hydrochloride, is delivered through a gastroretentive ethyl cellulose-based microparticulate system capable of floating on simulated gastric fluid for > 12 h. Preparation of microparticles is done by solvent evaporation technique with modification by using an ethanol co-solvent system. The formulated microspheres were free flowing with good packability and encapsulation efficiencies were up to 96%. Scanning electron microscopy confirmed porous, spherical particles in the size range 300-750 microm. Microspheres showed excellent buoyancy and a biphasic controlled release pattern with 12h. In vivo bioavailability studies performed on rabbits and T(max), C(max), AUC were calculated and confirmed significant improvement in bioavailability. The data obtained thus suggests that a microparticulate floating delivery system can be successfully designed to give controlled drug delivery, improved oral bioavailability and many other desirable characteristics.