生物黏附给药新剂型的发展近况

生物黏附给药系统(bioadhesive drug delivery system,BDDS)是现代给药剂型中一个新兴分支。生物黏附制剂是一类以生物黏附材料为药物载体,通过生物黏附作用长时间黏附于黏膜而发挥疗效的药物制剂。与其他给药剂型相比,生物黏附制剂有以下主要优点:①载体多由具有生物黏附材料所组成,对黏膜都有不同程度的黏附作用,可以延长释药     

生物黏附给药系统新剂型

系统查阅国内外有关生物黏附给药系统及生物黏附制剂的相关文献,进行归纳总结。生物黏附制剂可黏附于特定部位来控制药物释放速率,提高药物浓度,减少不良反应,增加疗效。其开发积极推动了制剂现代化的发展。     

凝集素介导的生物黏附微粒制剂研发趋势

阐述了第二代生物黏附微粒制剂的概念及黏附机制，介绍了影响凝集素黏附性能的因素和凝集素的类型，并对该系统的应用及发展趋势进行了概述。生物黏附释药系统作为一种新颖的药物释放系统，以特有的靶向性，缓、控释等优势成为很有前途的给药系统。其中凝集素介导的第二代生物黏附给药系统具有特异靶向性，微粒制剂又在提高药物稳定性、控制药物释放等方面具有优势。     

生物黏附药物传输系统研究进展

生物黏附药物传输系统(bioadhesive drug delivery system,BDDS)是以具有生物黏附性能的天然或合成的高分子材料作为药物载体,将其置于人体特定部位而缓慢释放药物的一种给药系统。生物黏附释药系统的作用部位包括各种腔     

新型胃滞留给药系统的研究进展

目的介绍新型胃滞留给药系统近年来的研究进展,为研究开发胃滞留制剂提供参考。方法通过查阅近年国内外相关文献,进行分析、整理和归纳。结果胃滞留给药系统能改善药物吸收,有效提高生物利用度,其中,以漂浮型、生物黏附型、膨胀型等三类胃滞留给药系统的研究较多。结论随着对胃滞留给药系统的深入研究,以及新型药用高分子材料的开发和制剂新技术的发展,胃滞留制剂具有广阔的应用前景。     

鼻黏膜生物黏附给药系统的研究进展

从影响鼻黏膜黏附和药物吸收的因素、鼻黏膜生物黏附给药系统的种类、鼻用生物黏附制剂的安全性等3个方面介绍了鼻黏膜生物黏附给药系统的研究进展.     

口服缓控释剂型结构对体外释药的影响

目的：综述近年口服缓控释制剂剂型结构对体外释药的影响，为缓释制剂研究提供参考。方法：查阅近年国内外相关文献，对常见的骨架型、包衣型、渗透泵型、微囊型、混合型等白服缓控释制剂的剂型结构及其对体外释药的影响分别加以概述。结果：同一药物，可以考虑制成不同的剂型结构，同一剂型结构又可以根据需求制成不同的剂型。结论：口服缓控释制剂剂型结构对体外释药有较大的影响。     

三七总皂苷鼻腔用制剂的研究

目的研究能够提高三七总皂苷生物利用度的给药途径和制剂。方法采用鼻腔给药筛选提高药物生物利用度的适宜制剂。结果本试验中制备的制剂在不引起黏膜刺激性的条件下，大幅度提高了PNS的生物利用度。结论可从给药途径和剂型两方面考虑提高药物吸收，降低刺激性。     

干扰素缓释给药系统的研究进展

目的:介绍干扰素缓释给药系统研究进展。方法:综述了近年来国内外干扰素缓释给药系统的研究状况。结果:阐明了不同干扰素缓释剂型的处方工艺,释药特点、存在的问题。结论:开发研究该类剂型仍需解决许多问题,目前长效缓释注射剂是干扰素缓释给药系统中较理想的应用剂型。     

漂浮-生物黏附协同作用制剂的研究进展

目的介绍漂浮-生物黏附协同作用制剂研究进展。方法对漂浮-生物黏附协同作用制剂的作用特点、制备方法及体外评价方法进行综述。结果该制剂可以延长药物在胃内的滞留时间,提高生物利用度。结论随着研究的深入,漂浮-生物黏附制剂将逐步受到重视,成为常用的药物新剂型之一。     

Exploring novel approaches to vaginal drug delivery

Vaginal route serves as a potential site of drug administration for local and systemic absorption of a variety of therapeutic agents. Despite being a non- invasive route of drug administration, the vagina has not been extensively explored as compared to other routes. Intravaginal drug delivery has been traditionally restricted to delivery of antinfectives to the local vaginal cavity. Concerted efforts have been made in the recent past to rediscover the vaginal route as a potential route for the delivery of therapeutically important molecules, proteins, peptides, small interfering RNAs, oligonucleotides, antigens, vaccines and hormones. The understanding of vaginal physiology has led to the design of specific intravaginal drug delivery systems to reach the systemic circulation. To overcome the limitations of conventional dosage forms administered through vaginal route various novel approaches like the use of mucoadhesive or bioadhesive polymers, pH- or temperature-sensitive polymers, liposomes, nanoemulsions, nanoparticles, vaginal inserts, multiple emulsions and hydrogels have been designed which enable controlled and prolonged release of drugs. The present article is a comprehensive review of the research and patents encompassing conventional dosage forms used for vaginal drug delivery with emphasis on newer platform technologies pertaining to intravaginal administration.     

Ethnic or racial differences revisited: impact of dosage regimen and dosage form on pharmacokinetics and pharmacodynamics

Ethnic or racial differences in pharmacokinetics and pharmacodynamics have been attributed to the distinctions in the genetic, physiological and pathological factors between ethnic/racial groups. These pharmacokinetic/pharmacodynamic differences are also known to be influenced by several extrinsic factors such as socioeconomic background, culture, diet and environment. However, it is noted that other factors related to dosage regimen and dosage form have largely been ignored or overlooked when conducting or analysing pharmacokinetic/pharmacodynamic studies in relation to ethnicity/race. Potential interactions can arise between the characteristics of ethnicity/race and a unique feature of dosage regimen or dosage form used in the study, which may partly account for the observed pharmacokinetic/pharmacodynamic differences between ethnic/racial groups. Ethnic/racial differences in pharmacokinetics/pharmacodynamics can occur from drug administration through a specific route that imparts distinct pattern of absorption, distribution, transport, metabolism or excretion. For example, racial differences in the first-pass metabolism of a drug following oral administration may not be relevant when the drug is applied to the skin. On the other hand, ethnic/racial difference in pharmacokinetics/pharmacodynamics can also happen via two different routes of drug delivery, with varying levels of dissimilarity between routes. For example, greater ethnic/racial differences were observed in oral clearance than in systemic clearance of some drugs, which might be explained by the pre-systemic factors involved in the oral administration as opposed to the intravenous administration. Similarly, changes in the dose frequency and/or duration may have profound impact on the ethnic/racial differences in pharmacokinetic/pharmacodynamic outcome. Saturation of enzymes, transporters or receptors at high drug concentrations is a possible reason for many observed ethnic/racial discrepancies between single- and multiple-dose regimens, or between low- and high-dose administrations. The presence of genetic polymorphism of enzymes and/or transporters can further complicate the analysis of pharmacokinetic/pharmacodynamic data in ethnic/racial populations. Even within the same dosage regimen, the use of different dosage forms may trigger significantly different pharmacokinetic/pharmacodynamic responses in various ethnic/racial groups, given that different dosage forms may exhibit different rates of drug release, may release the drug at different sites, and/or have different retention times at specific sites of the body. It is thus cautioned that the pharmacokinetic/pharmacodynamic data obtained from different ethnic/racial groups cannot be indiscriminately compared or combined for analysis if there is a lack of homogeneity in the apparent 'extrinsic' factors, including dosage regimen and dosage form.     

国内外不同年龄段儿童用药剂型的比较与思考

目的：分析我国不同年龄段儿童用药剂型的现状，比较国内外儿童用药剂型的差异，探讨促进我国儿童安全合理用药的措施。方法：通过比较欧洲药物评价局对不同年龄段儿童用药推荐剂型与我国儿童用药常用剂型的差异，分析我国儿童用药存在的问题。结果：我国儿童用药常用剂型单一、数量少，很难满足实际需求，且缺乏针对不同年龄段儿童使用药物剂型的研究。结论：借鉴国际相关经验，促进针对不同年龄段儿童剂型的研发，并开展儿童安全服用固体制剂的教育和培训，促进儿童合理用药。     

Novel modes of antifungal drug administration

Administration of antifungals by routes other than that for which the agent was designed or approved have been utilised in attempts to provide directed therapy, reduce adverse effects and improve drug penetration into selected infection sites, such as the central nervous system, lungs and peritoneum. The most widely investigated agent utilising a novel method of drug delivery is amphotericin B. Dose forms for this agent include topicals (aerosol, nasal spray, irrigations, pastes, absorbable sponges, impregnated bone cement and gelatin), oral dosage forms (solutions, suspensions, tablets and so on) and ophthalmic preparations (drops, ointments and injections). Amphotericin B has been administered by routes such as oral, endobronchial, intrathecal, intracisternal, intra-articular, intraperitoneal, ophthalmic and as an antibiotic ‘line lock’. Nystatin has been administered as an aerosol, percutaneous paste and bladder washes. Azoles, such as miconazole, fluconazole, ketoconazole and posaconazole, have been administered by novel methods but to a lesser degree. Most of these reports involve miconazole. The dose forms and routes of administration for azoles have included irrigants (bladder, joint), ophthalmic preparations (eye drops, intraocular injections, ointments), impregnated bone cement, endobronchial and intrathecal administration. Finally, both methylene blue (bladder washes) and flucytosine (peritoneal lavage, ophthalmic eye drops) have also been employed. Adequate evaluations of both the safety and efficacy of these therapies are most often hindered by prior or concomitant antifungal therapies, comorbidities and the lack of controlled clinical trials. In addition, the availability of newer treatment options, which demonstrate significant improvement in drug distribution and treatment-related adverse effects make many such novel modes of administration less practical or necessary. In contrast, the inhalation of antifungal aerosols, such as amphotericin B, is rapidly becoming a viable prophylactic option.     

Novel modes of antifungal drug administration

Administration of antifungals by routes other than that for which the agent was designed or approved have been utilised in attempts to provide directed therapy, reduce adverse effects and improve drug penetration into selected infection sites, such as the central nervous system, lungs and peritoneum. The most widely investigated agent utilising a novel method of drug delivery is amphotericin B. Dose forms for this agent include topicals (aerosol, nasal spray, irrigations, pastes, absorbable sponges, impregnated bone cement and gelatin), oral dosage forms (solutions, suspensions, tablets and so on) and ophthalmic preparations (drops, ointments and injections). Amphotericin B has been administered by routes such as oral, endobronchial, intrathecal, intracisternal, intra-articular, intraperitoneal, ophthalmic and as an antibiotic 'line lock'. Nystatin has been administered as an aerosol, percutaneous paste and bladder washes. Azoles, such as miconazole, fluconazole, ketoconazole and posaconazole, have been administered by novel methods but to a lesser degree. Most of these reports involve miconazole. The dose forms and routes of administration for azoles have included irrigants (bladder, joint), ophthalmic preparations (eye drops, intraocular injections, ointments), impregnated bone cement, endobronchial and intrathecal administration. Finally, both methylene blue (bladder washes) and flucytosine (peritoneal lavage, ophthalmic eye drops) have also been employed. Adequate evaluations of both the safety and efficacy of these therapies are most often hindered by prior or concomitant antifungal therapies, comorbidities and the lack of controlled clinical trials. In addition, the availability of newer treatment options, which demonstrate significant improvement in drug distribution and treatment-related adverse effects make many such novel modes of administration less practical or necessary. In contrast, the inhalation of antifungal aerosols, such as amphotericin B, is rapidly becoming a viable prophylactic option.     

Minimizing bioavailability variations with oral controlled release formulations

Despite various routes of drug delivery being explored, the oral route has continued to be the most popular route of drug administration. However, the complexities associated with the gastrointestinal tract lead to variations in the rate and extent of bioavailability of drugs administered as oral dosage forms. This variation in the bioavailability of drugs is responsible for the majority of adverse effects, lack of efficacy, and development of tolerance, etc. This review explores the possibilities of minimizing these bioavailability variations with the use of oral controlled release (CR) dosage forms. The use of CR preparations, in lieu of the immediate preparations in itself, leads to better control over plasma levels. Furthermore, the additional benefits offered by CR products, such as the reduction in first-pass metabolism, enhanced and reproducible bioavailability with gastro retentive preparations, overcoming circadian rhythm variations, and the lesser effect of fed condition on bioavailability, can be effectively utilized for bioavailability variation minimization. However, CR products cannot be use indiscriminately. The use of CR products to serve the purpose of bioavailability variation minimization should be based on due consideration to the role of metabolizing enzymes, the permeability variations, and the area available for absorption.     

阿片类癌痛治疗药物制剂的研究进展

目的梳理阿片类癌痛治疗药物常规剂型和新剂型,为相关剂型的临床合理选择和应用提供依据。方法主要对治疗癌痛的阿片类常规剂型（固体制剂,半固体制剂,液体制剂等）和新剂型（口含剂,喷雾剂,泡腾片等）的文献报道进行归纳分析。结果目前国内外强阿片类癌痛治疗药物存在多种剂型,无创给药的制剂仍然是使用最为广泛和依从性较好的剂型。结论根据不同给药途径的特点,选择切实有效的阿片类给药剂型,做到最大限度地减轻患者痛苦,提高癌症患者生活质量。     

Nasal route and drug delivery systems

Nasal drug administration has been used as an alternative route for the systemic availability of drugs restricted to intravenous administration. This is due to the large surface area, porous endothelial membrane, high total blood flow, the avoidance of first-pass metabolism, and ready accessibility. The nasal administration of drugs, including numerous compound, peptide and protein drugs, for systemic medication has been widely investigated in recent years. Drugs are cleared rapidly from the nasal cavity after intranasal administration, resulting in rapid systemic drug absorption. Several approaches are here discussed for increasing the residence time of drug formulations in the nasal cavity, resulting in improved nasal drug absorption. The article highlights the importance and advantages of the drug delivery systems applied via the nasal route, which have bioadhesive properties. Bioadhesive, or more appropriately, mucoadhesive systems have been prepared for both oral and peroral administration in the past. The nasal mucosa presents an ideal site for bioadhesive drug delivery systems. In this review we discuss the effects of microspheres and other bioadhesive drug delivery systems on nasal drug absorption. Drug delivery systems, such as microspheres, liposomes and gels have been demonstrated to have good bioadhesive characteristics and that swell easily when in contact with the nasal mucosa. These drug delivery systems have the ability to control the rate of drug clearance from the nasal cavity as well as protect the drug from enzymatic degradation in nasal secretions. The mechanisms and effectiveness of these drug delivery systems are described in order to guide the development of specific and effective therapies for the future development of peptide preparations and other drugs that otherwise should be administered parenterally. As a consequence, bioavailability and residence time of the drugs that are administered via the nasal route can be increased by bioadhesive drug delivery systems. Although the majority of this work involving the use of microspheres, liposomes and gels is limited to the delivery of macromolecules (e.g., insulin and growth hormone), the general principles involved could be applied to other drug candidates. It must be emphasized that many drugs can be absorbed well if the contact time between formulation and the nasal mucosa is optimized.     

生物粘附材料的研究进展

目的系统地了解生物粘附材料的类别和性质 ,生物粘附的机理 ,影响生物粘附的因素 ,生物粘附性的实验研究方法 ,生物粘附材料在制剂中的应用及存在的问题。方法对近期的文献进行检索、分类和整理。结果对生物粘附传递系统的研究比较活跃 ,但性能优良的生物粘附材料的品种较少 ,生物粘附的机理尚不完全清楚 ,生物粘附性的实验研究方法有待于完善。结论生物粘附传递系统将具有较好的应用前景。     

A HAART‐Breaking Review of Alternative Antiretroviral Administration: Practical Considerations with Crushing and Enteral Tube Scenarios

Selection of an appropriate antiretroviral regimen for the patient infected with human immunodeficiency virus can be challenging, as various considerations must be taken into account including viral resistance mutations, patient comorbidities, drug interactions, and the potential for drug‐related adverse effects and toxicities. Treatment is further complicated when a clinical scenario arises requiring an alteration in the dosage form. Factors ranging from dysphagia to administration through an enteral feeding tube can affect decisions regarding antiretroviral dosage forms. Limited pharmacokinetic data exist regarding the alteration of antiretroviral medications from their original form. Bioavailability may vary substantially between dosage forms, which can lead to unpredictable drug concentrations. Supratherapeutic or subtherapeutic antiretroviral drug concentrations can result in increased toxicity, virologic failure, or the emergence of drug resistance. We performed a systematic literature search to review the available antiretroviral literature on the modification of solid dosage forms as well as alternative routes of administration of oral antiretroviral agents and their application to clinical practice.