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。     

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。     

胃内滞留制剂的研究进展

延长制剂在胃内的滞留时间可以增加药物在胃部的吸收，从而降低全身毒副作用，提高生物利用度。依据药物制剂在体内的大小、比重及作用机制分为漂浮型胃内滞留系统、生物粘附型胃内滞留系统、漂浮与生物粘附协同型胃内滞留系统、高密度型胃内滞留系统和阻塞型胃内滞留系统等。本文就胃内滞留制剂研究的新进展作一综述。     

胃内滞留释药系统的研究新进展

介绍近年来胃内滞留释药系统的研究进展。胃内滞留释药系统可增加以胃肠道上部吸收为主的药物的吸收,延长药物作用时间,提高药物生物利用度。目前胃内滞留释药系统主要有5种类型：胃内漂浮型、胃内黏附型、胃内膨胀型、胃底沉降型和磁性胃内滞留型。     

缓／控释制剂的国外研究动向

８０年代末，制剂研究开始转向新型给药系统。当前，研究最热门的仍为缓／控释给药系统。本文从胃内滞留型给药系统、脉冲式给药系统、结肠定位给药系统及自动调节给药系统４个侧面概述国外研究现状和发展趋势。     

胃滞留型给药系统研究概况

胃滞留制剂可以增加以胃肠道上部吸收为主的药物的吸收,延长药物作用时间,减轻药物在胃肠道的局部刺激,提高生物利用度。依据药物制剂在体内的大小、比重及作用机制分为漂浮型胃内滞留系统、膨胀型胃内滞留系统、生物黏附型胃内滞留系统等。     

胃滞留-漂浮型给药系统研究进展

胃滞留-漂浮型给药系统以其特有的缓控释优势而成为很有前途的剂型。综述各类胃滞留-漂浮型制剂的作用原理、所用辅料、制备方法、优缺点及其体内评价方法。     

胃内漂浮给药系统的研究进展

胃内漂浮给药系统是通过制剂手段来延长胃内滞留时间,达到增加药物吸收,提高生物利用度的目的.就该类制剂的技术进步、性能评价及前景与局限性进行综述.     

口服定位释药系统

本文对控制释药部位的药物传输系统——口服定位释药系统进行了综述。口服定位释药系统主要分为胃内滞留型和结肠定位释药系统两类。胃内滞留型释药系统包括胃内漂浮型、胃内膨胀型和胃壁粘附型等。结肠定位释药系统包括时控型、pH敏感型、酶解型、以及结肠靶向生物粘附系统。     

口服定位释药系统

本文对控制释药部位的药物传输系统－口服定位释药系统进行了综述。口服定位释药系统主要分为胃内滞留型和结肠定位释药系统两类。胃内滞留型释药系统包括胃内漂浮型，胃内膨胀型和胃壁粘附型等。结肠定位释药系统包括时控制，pH敏感型，酶解型，以及结肠靶向生物粘附系统。     

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.     

Preparation and characterization of superporous hydrogels as gastroretentive drug delivery system for rosiglitazone maleate

BACKGROUND AND THE PURPOSE OF THE STUDY: Many drugs which have narrow therapeutic window and are absorbed mainly in stomach have been developed as gastroretentive delivery system. Rosiglitazone maleate, an anti-diabetic, is highly unstable at basic pH and is extensively absorbed from the stomach. Hence there is a need to develop a gastroretentive system. In this study a superporous hydrogel was developed as a gastroretentive drug delivery system. METHODS: Chitosan/poly(vinyl alcohol) interpenetrating polymer network type superporous hydrogels were prepared using a gas foaming method employing glyoxal as the crosslinking agent for Rosiglitazone maleate. Sodium bicarbonate was applied as a foaming agent to introduce the porous structure. Swelling behaviors of superporous hydrogel in acidic solution were studied to investigate their applications for gastric retention device. The optimum preparation condition of superporous hydrogels was obtained from the gelation kinetics. FT-IR, scanning electron microscopy, porosity and swelling ratio studies were used to characterize these polymers. In vitro drug release studies were also carried out. RESULTS: The introduction of a small amount of Poly(Vinyl Alcohol) enhanced the mechanical strength but slightly reduced the swelling ratio. The prepared superporous hydrogels were highly sensitive to pH of swelling media, and showed reversible swelling and de-swelling behaviors maintaining their mechanical stability. The degradation kinetics in simulated gastric fluid showed that it had biodegradability. Swelling was dependent on the amount of chitosan and crosslinker. The drug release from superporous hydrogels was sustained for 6 hrs. MAJOR CONCLUSION: The studies showed that chitosan-based superporous hydrogels could be used as a gastroretentive drug delivery system for rosiglitazone maleate in view of their swelling and prolonged drug release characteristics in acidic pH.     

Linseed hydrogel based floating drug delivery system for fluoroquinolone antibiotics: Design,in vitro drug release and in vivo real-time floating detection

Herein, we designed a novel gastroretentive drug delivery system as floating matrix tablets based on a polysaccharide material from linseeds (Linum usitatissimum L.) for fluoroquinolone antibiotics. A number of formulations were designed with a combination of linseed hydrogel (LSH) and different excipients to obtain a desired sustained release profile of moxifloxacin. The drug release study was performed basically at pH 1.2. However, the tablet may pass through the stomach to intestine due to certain reasons then it also offered sustained drug release at intestinal pH 4.5, 6.8 and 7.4, as well. Results indicated that sustained moxifloxacin release was directly proportional to the concentration of LSH and the release of drug followed non-Fickian diffusion. SEM of the tablets indicated porous nature of LSH with elongated channels which contributed to the swelling of the tablet and then facilitated the discharge of moxifloxacin from the core of the tablet. In vivo X-ray study was performed to assess disintegration and real-time floating of tablet that confirmed its presence for 6 h in the stomach. These findings indicated that LSH can be used to develop novel gastroretentive sustained release drug delivery systems with the double advantage of sustained drug release at all pH of GIT.     

Chitosan-based gastroretentive floating drug delivery technology: an updated review

INTRODUCTION: Gastroretentive floating drug delivery systems have emerged as efficient approaches for enhancing the bioavailability and controlled delivery of various therapeutic agents. Significant advancements exploiting chitosan have been made worldwide, in order to investigate these systems according to patient requirements, both in terms of therapeutic efficacy as well as patient compliance. Such systems precisely control the release rate of the target drug to a specific site, which facilitates an enormous impact on health care. AREAS COVERED: Different novel strategies have been undertaken for the development of various gastric floating dosage forms utilizing chitosan as a promising excipient. The present paper is an earnest attempt to provide new insights on various physicochemical and biological characteristics of chitosan, along with its potential applications in a wide array of biomedical approaches. Numerous and significant research findings in the vistas of chitosan-based gastroretentive floating drug delivery technology are also discussed. EXPERT OPINION: Chitosan has been considered as a unique and efficacious agent possessing a myriad spectrum of desired characteristics. It is emphasized that recent scientific advancements in the use of this excipient as a carrier will yield new generation gastroretentive drug delivery systems, with better pharmacotherapeutic interventions. Further studies are required to unveil the hidden beneficial properties of chitosan and its derivatives, to obtain newer delivery systems which may hold tremendous prospects in the near future.     

甲硝唑胃部滞留制剂的制备

目的为更好地清除幽门螺旋杆菌,制备同时具有缓释、漂浮、黏附特性的甲硝唑胃部滞留制剂。方法采用挤出滚圆法制备丸心,流化床包衣法制备甲硝唑缓释漂浮黏附微丸。EudragitNE30D为缓释层,NaHCO3为产气层,EudragitRL 30D为阻滞层,Carbopol 934P为黏附层,考察不同包衣增量情况下,各微丸的释药行为,在0.1 mol.L-1HCl中的漂浮性能,及离体大鼠胃黏膜上的黏附能力。结果丸心外包质量分数为3%的EudragitNE 30D,质量分数为9%的NaHCO3,质量分数为10%的EudragitRL 30D,质量分数为5%的Carbopol 934P的微丸,能实现缓释12 h、4 min起漂、持续漂浮12 h,漂浮率大于95%、黏附率为100%。结论所制备的甲硝唑胃部滞留制剂,同时具备缓释的释药行为、优良的漂浮能力、良好的黏附特征。进而能增加甲硝唑的胃部滞留时间,延长药物与幽门螺旋杆菌的接触时间,提高甲硝唑抗幽门螺旋杆菌的疗效。     

Formulation development of gastroretentive tablets of lamivudine using the floating-bioadhesive potential of optimized polymer blends

Objectives The current studies entail successful formulation of optimized gastroretentive tablets of lamivudine using the floating‐bioadhesive potential of carbomers and cellulosic polymers, and their subsequent in‐vitro and in‐vivo evaluation in animals and humans. Methods Effervescent floating‐bioadhesive hydrophilic matrices were prepared and evaluated for in‐vitro drug release, floatation and ex‐vivo bioadhesive strength. The optimal composition of polymer blends was systematically chosen using central composite design and overlay plots. Pharmacokinetic studies were carried out in rabbits, and various levels of in‐vitro/in‐vivo correlation (IVIVC) were established. In‐vivo gamma scintigraphic studies were performed in human volunteers using ^99mTc to evaluate formulation retention in the gastric milieu. Key findings The optimized formulation exhibited excellent bioadhesive and floatational characteristics besides possessing adequate drug‐release control and pharmacokinetic extension of plasma levels. The successful establishment of various levels of IVIVC substantiated the judicious choice of in‐vitro dissolution media for simulating the in‐vivo conditions. In‐vivo gamma scintigraphic studies ratified the gastroretentive characteristics of the optimized formulation with a retention time of 5 h or more. Conclusions Besides unravelling the polymer synergism, the study helped in developing an optimal once‐a‐day gastroretentive drug delivery system with improved bioavailability potential exhibiting excellent swelling, floating and bioadhesive characteristics.     

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.     

Chitosan-based gastroretentive floating drug delivery technology: an updated review

Introduction: Gastroretentive floating drug delivery systems have emerged as efficient approaches for enhancing the bioavailability and controlled delivery of various therapeutic agents. Significant advancements exploiting chitosan have been made worldwide, in order to investigate these systems according to patient requirements, both in terms of therapeutic efficacy as well as patient compliance. Such systems precisely control the release rate of the target drug to a specific site, which facilitates an enormous impact on health care.

Areas covered: Different novel strategies have been undertaken for the development of various gastric floating dosage forms utilizing chitosan as a promising excipient. The present paper is an earnest attempt to provide new insights on various physicochemical and biological characteristics of chitosan, along with its potential applications in a wide array of biomedical approaches. Numerous and significant research findings in the vistas of chitosan-based gastroretentive floating drug delivery technology are also discussed.

Expert opinion: Chitosan has been considered as a unique and efficacious agent possessing a myriad spectrum of desired characteristics. It is emphasized that recent scientific advancements in the use of this excipient as a carrier will yield new generation gastroretentive drug delivery systems, with better pharmacotherapeutic interventions. Further studies are required to unveil the hidden beneficial properties of chitosan and its derivatives, to obtain newer delivery systems which may hold tremendous prospects in the near future.     

Systems for region selective drug delivery in the gastrointestinal tract: biopharmaceutical considerations

BACKGROUND: The design of a proper region-specific oral drug delivery system has to take into consideration the differences in anatomy, physiology and absorption characteristics that exist between segments within the gastrointestinal (GI) tract, as well as transit kinetics of the dosage form and the site of drug release within the GI tract. OBJECTIVE: The aim of this review is to examine the various biopharmaceutical aspects of region-specific drug delivery in the GI tract. METHODS: This review is mainly focused on pharmacokinetic and pharmacodynamic aspects of region-selective drug delivery with special emphasis on drug absorption pathways (para- and transcellular, absorption and efflux transporters, lymphatic uptake etc.). It includes a discussion of gastroretentive systems, colonic delivery, and lipid-based formulations. The review also addresses targeted therapy of local diseases within the GI tract. CONCLUSIONS: The advances in pharmaceutical technology allow for the development of a variety of region-specific drug delivery systems for oral administration to optimize local and systemic therapy.