口腔黏膜给药进展

自从 1 847年 Sobrero首次发现硝酸甘油在口腔黏膜吸收以来 ,人们相继报道了其他药物的吸收情况[1] ,1 9世纪 70年代以来进入快速发展阶段 ,80年代后期细胞培养技术的应用使其进展更为迅猛 ,目前国外已有 1 8个品种上市[2 ] 。口腔黏膜给药具有局部作用 (使药物到达黏膜、牙组织、牙周袋等 )和全身作用 (给药部位包括舌下、颊和齿龈 )。与口服相比有许多优点 :可避免胃肠道影响和肝脏首过效应 ;血液供应良好 ,利于吸收 ;易于给药 ,易于除去。口腔黏膜的通透性较鼻黏膜差 ,但大于皮肤 ,因此强效药物通过颊内或舌下给药可望达到治疗浓度。另…     

黏膜给药的研究进展

黏膜给药指使用合适的载体将药物通过人体黏膜部位如鼻黏膜、口腔黏膜、眼黏膜、直肠黏膜、子宫及阴道黏膜,进入局部或全身血液循环而起药效的给药方式[1]。近年来,黏膜给药由于具有生物利用度(F)高、吸收起效迅速、使用方便等优点,而受到科研工作者的高度关注。以下仅就鼻、口腔黏膜给药的优点、主要途径以及常用剂型综述如下。     

替硝唑载药系统与给药方法的研究进展

目的：介绍替硝唑载药系统与给药方法的研究进展。方法：系统查阅近年来有关替硝唑载药系统与给药方法的研究报道，并进行综合分析。结果：为今后替硝唑载药系统和给药方案的深入研究提供了部分科学依据。为满足替硝唑临床治疗的需要，可以从其载体材料、制备方法、工艺条件等方面进行综合研究，从而研制出疗效佳、给药便捷的替硝唑载药系统。结论：替硝唑载药系统具有良好的发展前景。     

颊粘膜给药系统的研究概述

颊粘膜给药是生物粘附性制剂中的一种。生物粘附性制剂近年来发展很快 ,该制剂在控制药物释放、提高药物生物利用度和靶向给药等方面具有明显优势。在颊粘膜给药系统中 ,药物通过颊粘膜可以直接入血 ,避免肝首过作用及胃肠的代谢 ,故对于肝首过作用显著和口服利用度低的药物有开发价值。此外 ,颊粘膜给药既能迅速发挥药效 ,又能长时间维持药效 ,因而具有缓释的作用 ,较只有迅速显效作用的舌下给药有更广泛的应用范围。现将近年来国内外有关颊粘膜给药系统的研究状况 ,概述如下 :1　生物粘附1 1　生物粘附机制[1]生物粘附 (ｂｉｏａｄｈｅｓ…     

口腔颊粘膜给药系统及其质量评价

介绍了口腔颊粘膜给药系统,并对其制剂的粘附力、粘附时间、膨胀率、均匀度和有效性等质量评价方面进行了综述。作为新型给药系统,颊粘膜给药系统的成熟与发展还需要在质量评价等方面进行深入研究。     

多层片给药系统在定位和控制释药中的应用

多层片给药系统由含药片层及屏障层组成，通过屏障层控制药物的释放。综述近年来该给药系统在缓控释方面的研究进展，介绍其在定位释药（颊部黏膜给药、胃内定位释药和结肠定位给药）和控制释药形式（双相型释药、零级释药、双峰型释药和延时型释药）方面的应用。     

抗心律失常药新的给药途径

心律失常是一种严重的疾病，传统的给药方法如青注或口服往往疗效一般或产生全身毒性反应。近年来，国外采用心外膜药物聚合物骨架粘附给药和离子导入给药，产生了较好的效果。其局部药物浓度高，起效迅速，能进行药物控释，且能避免全身的不良反应，是一种很有发展前景的给药方式，本文综述了有关这方面的研究进展。     

右美托咪定不同给药途径对区域麻醉局麻药协同作用影响的研究进展

目的:为右美托咪定(DEX)在区域麻醉中的临床科学研究提供参考。方法:以"右美托咪定""佐剂""蛛网膜下腔麻醉""硬膜外麻醉""区域麻醉""神经传导阻滞""局麻""Dexmedetomidine""Adjuvant""Spinal anesthesia""Epidural anesthesia""Regional anesthesia""Nerve block""Local anesthesia"等为关键词,在中国知网、万方、维普网、PubMed、Embase等数据库中组合查询1990年1月-2019年2月发表的相关文献,对神经周围注射(PN)、静脉输注(IV)、经鼻滴入(IN)、肌内注射、口腔颊黏膜给药等DEX的不同给药途径对区域麻醉的影响进行汇总与分析。结果与结论:共检索到相关文献1 012篇,其中有效文献56篇。不论是椎管内麻醉,还是外周神经阻滞,DEX都具有协同局麻药的作用,可延长局麻药镇痛持续时间,但因区域麻醉部位的不同,其协同作用存在差异。PN-DEX对于区域麻醉影响的研究最多,IV-DEX的研究次之,其对区域麻醉时局麻药的协同作用较PN-DEX弱,但用药时间点的选择和给药速度更灵活;IN-DEX给药方式适合儿童;经口腔颊黏膜给药或肌内注射等途径对于区域麻醉协同作用的研究极少且临床实用性低。进一步的机制研究有助于明确DEX协同局麻药的作用和不同给药途径对于区域麻醉协同作用的差异。给药途径上,除IV-DEX外,PN-DEX、IN-DEX、肌内注射、口腔颊黏膜给药都属超说明书用药,临床的安全性有待于进一步明确。不论哪种给药途径,低血压和心动过缓都是需要注意的副作用,特别是对于老年人、孕产妇、儿童等特殊人群,因相关安全性研究较少,故临床应用仍需慎重。     

壳聚糖微球给药系统

主要介绍壳聚糖微球的制备方法，影响其载药的主要因素，及其在缓控释、靶向给药、黏膜给药、生物大分子给药等方面的应用。近年来壳聚糖微球作为新型给药系统备受关注。     

微针在口腔黏膜给药系统中的研究进展

口腔黏膜给药系统是近年来发展的一种新型给药系统,与传统的口服给药途径相比,可以避免胃肠道酶代谢、酸降解及肝脏首过作用,进而提高药物生物利用度,发挥局部或全身治疗和预防作用。但是口腔黏膜的物理屏障会限制药物的吸收,而微针可突破该障碍,改善药物的渗透。本文简述了口腔黏膜给药的优缺点,介绍了微针的分类及国内微针企业的发展情况,讨论了微针在口腔黏膜给药系统的研究进展,以期有更多新的口腔黏膜制剂推向市场。     

Buccal drug delivery

Buccal formulations have been developed to allow prolonged localised therapy and enhanced systemic delivery. The buccal mucosa, however, while avoiding first-pass effects, is a formidable barrier to drug absorption, especially for biopharmaceutical products (proteins and oligonucleotides) arising from the recent advances in genomics and proteomics. The buccal route is typically used for extended drug delivery, so formulations that can be attached to the buccal mucosa are favoured. The bioadhesive polymers used in buccal drug delivery to retain a formulation are typically hydrophilic macro-molecules containing numerous hydrogen bonding groups. Newer second-generation bioadhesives have been developed and these include modified or new polymers that allow enhanced adhesion and/or drug delivery, in addition to site-specific ligands such as lectins. Over the last 20 years a wide range of formulations has been developed for buccal drug delivery (tablet, patch, liquids and semisolids) but comparatively few have found their way onto the market. Currently, this route is restricted to the delivery of a limited number of small lipophilic molecules that readily cross the buccal mucosa. However, this route could become a significant means for the delivery of a range of active agents in the coming years, if the barriers to buccal drug delivery are overcome. In particular, patient acceptability and the successful systemic delivery of large molecules (proteins, oligonucleotides and polysaccharides) via this route remains both a significant opportunity and challenge, and new/improved technologies may be required to address these.     

Buccal drug delivery

Buccal formulations have been developed to allow prolonged localised therapy and enhanced systemic delivery. The buccal mucosa, however, while avoiding first-pass effects, is a formidable barrier to drug absorption, especially for biopharmaceutical products (proteins and oligonucleotides) arising from the recent advances in genomics and proteomics. The buccal route is typically used for extended drug delivery, so formulations that can be attached to the buccal mucosa are favoured. The bioadhesive polymers used in buccal drug delivery to retain a formulation are typically hydrophilic macro-molecules containing numerous hydrogen bonding groups. Newer second-generation bioadhesives have been developed and these include modified or new polymers that allow enhanced adhesion and/or drug delivery, in addition to site-specific ligands such as lectins. Over the last 20 years a wide range of formulations has been developed for buccal drug delivery (tablet, patch, liquids and semisolids) but comparatively few have found their way onto the market. Currently, this route is restricted to the delivery of a limited number of small lipophilic molecules that readily cross the buccal mucosa. However, this route could become a significant means for the delivery of a range of active agents in the coming years, if the barriers to buccal drug delivery are overcome. In particular, patient acceptability and the successful systemic delivery of large molecules (proteins, oligonucleotides and polysaccharides) via this route remains both a significant opportunity and challenge, and new/improved technologies may be required to address these.     

Recent developments in buccal and sublingual delivery systems

INTRODUCTION: There have been several advances in the delivery of drugs through the buccal mucosa over the last 5 years, which have resulted in a number of new buccal delivery products appearing on the market. AREAS COVERED: This review discusses the most recent developments in the area of buccal and sublingual drug delivery, with a focus on marketed drugs. Likely future directions are also considered and reported. EXPERT OPINION: The future potential of buccal and sublingual delivery systems looks favorable. It is envisaged that in the future, buccal and sublingual delivery technologies will provide a platform for the successful delivery of vaccines and antigens. It is also foreseen that physical means of enhancing drug uptake (e.g., sonophoresis, iontophoresis and electroporation) will be commercialized for buccal delivery, thereby expanding the current drug candidate list for this area. The formulation of delivery systems for photosensitizers in photodynamic therapy is a potential emerging area, while buccal and sublingual delivery, in general, is attractive for the development of intellectual property.     

Recent developments in the use of bioadhesive systems for delivery of drugs to the oral cavity

The delivery of therapeutic agents to, or via, the oral cavity is limited by the efficient removal mechanisms that exist in this area. Bioadhesive formulations have been developed to allow prolonged localized therapy and enhanced systemic delivery. The oral mucosa however, while avoiding first-pass effects, is a formidable barrier to drug absorption, especially for "biopharmaceutical" products arising from the recent innovations in genomics and proteomics. Bioadhesive polymers are typically hydrophilic macromolecules containing numerous hydrogen-bonding groups. Second-generation bioadhesives include modified or new polymers that allow enhanced adhesion and/or drug delivery, along with site-specific ligands such as lectins. Over the last 20 years, a range of bioadhesive formulations have been developed for the oral cavity, but only comparatively few have found their way onto the market. This review will consider some recent developments in the use of bioadhesive buccal systems, notably the development of new polymers, advanced delivery systems, and the exploitation of the multifunctional properties of some bioadhesives.     

Mucoadhesive microspheres: a promising tool in drug delivery

Mucoadhesive polymers have recently gained interest among pharmaceutical scientists as a means of improving drug delivery by promoting the residence time and contact time of the dosage form with the mucous membranes. Mucoadhesion is the process whereby synthetic and natural polymers adhere to mucosal surfaces in the body. If these materials are then incorporated into pharmaceutical formulations, drug absorption by mucosal cells may be enhanced or the drug will be released at the site for an extended period of time. Microspheres, in general, have the potential to be used for targeted and controlled release drug delivery; however, coupling of mucoadhesive properties to microspheres has additional advantages like, a much more intimate contact with the mucus layer, efficient absorption and enhanced bioavailability of the drugs due to a high surface to volume ratio. The present review describes the potential applications of mucoadhesive microspheres as a novel carrier system to improve drug delivery by various routes of administration like buccal, oral, nasal, ocular, vaginal and rectal, either for systemic or for local effects. The mucoadhesive polymers, methods of preparation of microspheres and their in vitro and in vivo evaluation are also described.     

Recent developments in buccal and sublingual delivery systems

Introduction: There have been several advances in the delivery of drugs through the buccal mucosa over the last 5 years, which have resulted in a number of new buccal delivery products appearing on the market.

Areas covered: This review discusses the most recent developments in the area of buccal and sublingual drug delivery, with a focus on marketed drugs. Likely future directions are also considered and reported.

Expert opinion: The future potential of buccal and sublingual delivery systems looks favorable. It is envisaged that in the future, buccal and sublingual delivery technologies will provide a platform for the successful delivery of vaccines and antigens. It is also foreseen that physical means of enhancing drug uptake (e.g., sonophoresis, iontophoresis and electroporation) will be commercialized for buccal delivery, thereby expanding the current drug candidate list for this area. The formulation of delivery systems for photosensitizers in photodynamic therapy is a potential emerging area, while buccal and sublingual delivery, in general, is attractive for the development of intellectual property.     

Oromucosal films: from patient centricity to production by printing techniques

ABSTRACT

Introduction: Oromucosal films, comprising mucoadhesive buccal films (MBFs) and orodispersible films (ODFs), are considered patient-centric dosage forms. Target groups are patients with special needs. Various active pharmaceutical ingredients have been shown to be suitable for oromucosal film production. A shift is seen in the production techniques, from conventional solvent casting to printing techniques.

Areas covered: In this review, the patient acceptability of oromucosal films is discussed. An overview is given of the small molecule drugs, biopharmaceuticals and herbal extracts that have been incorporated so far. Finally, the current state of 2D and 3D printing techniques for production purposes is discussed.

Expert opinion: The patient-centric features are important for the further development and acceptance of this oral solid dosage form. Oromucosal films perfectly fit in the current attention for personalized medicine. Both MBFs and ODFs are intended for either a local or a systemic effect. For buccal absorption, sufficient mucoadhesion is one of the most important criteria an oromucosal film must comply with. For the preparation, the solvent casting technique is still predominately used. Some limitations of this production method can be tackled by printing techniques. However, these novel techniques introduce new requirements, yet to be set, for oromucosal film preparation.     

Chemical permeation enhancers for transbuccal drug delivery

Importance of the field: The buccal drug delivery system has been accepted as a potential non-invasive route of drug administration, with the advantages of avoidance of the first-pass metabolism, sustained therapeutic action and better patient compliance. However, transmucosal delivery of drugs by means of the buccal route is still very challenging. The main obstacles derive from the limited absorption area and from the barrier properties of the mucosa that have to be overcome for successful delivery drug molecules to the systemic circulation by this route.

Areas covered in this review: One long-standing approach for improving buccal drug delivery uses buccal absorption promoters, also called permeation enhancers. This requisite has fostered the study of permeation enhancers that will safely alter the permeability restrictions of the buccal mucosa. This review includes various classes of transmucosal chemical permeation enhancers and their mechanism of action. As enhancers influence drug delivery, further exploration of these compounds is required to understand their modifying action on the properties of buccal mucosa.

What the reader will gain: This review will help the readers in the selection of a suitable enhancer(s) for improving the buccal drug delivery for future endeavor.

Take home message: The authors imagine new buccal formulations bearing permeation enhancer(s) being commercialized in the coming years.     

The use of mucoadhesive polymers in buccal drug delivery

Buccal delivery of the desired drug using mucoadhesive polymers has been the subject of interest since the early 1980s. Advantages associated with buccal drug delivery have rendered this route of administration useful for a variety of drugs. This review highlights the use of mucoadhesive polymers in buccal drug delivery. Starting with a review of the oral mucosa, mechanism of drug permeation, and characteristics of the desired polymers, this article then proceeds to cover the theories behind the adhesion of bioadhesive polymers to the mucosal epithelium. Additionally, we focus on the new generation of mucoadhesive polymers such as thiolated polymers, followed by the recent mucoadhesive formulations for buccal drug delivery.     

多肽/微型蛋白类导向分子的研究进展

多肽药物因其相对分子质量小、生物活性高、易于修饰和规模化制备等特点,是新药研究的重要方向之一。除了直接作为候选药物或小分子药物设计的前体之外,多肽在药物开发中还有一类十分重要的应用：作为导向分子。多肽类导向分子与病灶部位靶标的特异性结合能够介导小分子药物或递药系统更有效地被靶细胞摄取,从而有望实现高效低毒的治疗。综述近年来多肽类导向分子的来源、优化以及发展趋势,以期为相关研究提供参考。