纳米载体提高难溶性药物口服生物利用度的研究进展

纳米载体是药剂学备受关注的研究领域,作为一类新型给药系统,它能显著提高难溶性药物的溶解度、生物利用度和稳定性,且具有明显的缓释作用,因此得到了广泛的应用。目前常用于提高难溶性药物口服生物利用度的纳米载体有纳米脂质体、固体脂质纳米粒、纳米胶束、和纳米结晶等,它们的粒径、表面性质及其释药环境等是影响纳米载体药物口服吸收的主要因素。本文对纳米载体提高难溶性药物口服生物利用度的研究进展作一综述。     

纳米结构脂质载体用于难溶性药物口服传递的研究进展

纳米结构脂质载体可以提高难溶性药物的口服生物利用度,是一种具有前景的难溶性药物口服传递系统。通过查阅文献,对纳米结构脂质载体常见的制备材料、方法,体外表征和释药,及提高难溶性药物口服生物利用度的机制进行综述。     

脂质类纳米载体在难溶性药物递送中的应用

随着新技术在药物研发中的广泛应用,大量有活性的难溶性候选药物涌现出来,但水溶性差的问题又严重制约了此类药物的开发。目前纳米载体作为难溶性药物递送系统的研究日益增多。本文综述了微乳、脂肪乳、脂质体、固体脂质纳米粒、纳米脂质载体、脂质纳米混悬剂和仿生载体等脂质类纳米载体在难溶性药物递送中的应用,旨在为产品的开发提供新策略。     

纳米药物晶体的制备技术研究进展

纳米药物晶体可解决多数难溶性药物的溶解度和溶出度问题,近年来成为难溶性药物给药系统研究的热点之一.本文着重综述了纳米药物晶体的制备技术,如沉淀法、分散法、乳化法和微乳化法、超临界流体结晶法等的研究进展.     

基于纳米载药技术的丹参难溶性成分在抗肿瘤治疗中的研究进展

丹参难溶性成分因能对抗多种恶性肿瘤而成为很好的抗肿瘤候选药物,但因其水溶性差、半衰期短、生物利用度低,极大限制了其临床应用。随着纳米技术的持续发展,基于纳米粒、脂质体、聚合物胶束等中药纳米给药系统能够很好地克服这些不足并被开发应用于临床。本文对近年报道的丹参难溶性成分纳米给药系统在抗肿瘤治疗中的研究进展进行综述,以期为今后进一步开发丹参难溶性成分的纳米给药系统提供理论依据。     

纳米给药系统的药动学及毒理学研究进展

纳米给药是药剂学领域研究颇多的1种新型药物递送体系,具有超微体积及特殊结构,在控释、缓释、靶向给药以及黏膜、局部给药中,可提高难溶性药物与多肽药物的生物利用度,降低不良反应,在基因工程等领域中也显示出独特的优势。笔者综述了近年来报道的纳米给药系统在药动学、毒理学方面的研究,并简要介绍了纳米给药系统在药剂学领域中的研究进展。     

纳米技术在口服难溶性药物的研究进展

据报道,有〉70%的化学合成药物存在难溶性问题[1],约40%的新化学实体（NCEs）因其难溶性而无法进入临床试验,使其应用受到很大程度的限制[2]。口服给药不仅方便且患者顺应性高,是新药首选的给药途径之一。但对于生物药剂学分类系统中的第Ⅱ类药物（即穿膜性好,但溶解度低而言,因在胃肠道中溶解度低或溶出速率慢,可能导致口服生物利用度低。因此,解决因药物难溶性引起的口服低吸收问题,可提高这类药物的口服生物利用度。解决药物难溶性主要有两条途径：①提高溶解度,增加药物溶出：提高难溶性药物溶解度或溶出速率的常用方法有成盐、改变药物晶型、使用增溶剂或减小粒径等;②应用纳米给药系统,将药物包入载体内部,使药物以载药传递体形式被肠道吸收。     

纳米结构脂质载体促进难溶性药物口服吸收机制的研究进展

纳米结构脂质载体（NLC）是药剂学备受关注的研究领域,作为一种性能优良的新型药物传递系统,能促进难溶性药物的口服吸收。探讨并总结纳米结构脂质载体促进难溶性药物口服吸收的机制。     

泊洛沙姆为载体的疏水性药物新剂型研究进展

目的综述高分子聚合物辅料泊洛沙姆近年来在提高疏水性药物溶解吸收和生物利用度方面的最新应用进展。方法查阅近2～3年来国内外研究文献,总结以泊洛沙姆407及泊洛沙姆188为载体的的各种疏水性药物给药新剂型及其载药特性和优点。结果以两类泊洛沙姆制备的给药新剂型主要有原位凝胶、固体分散体、纳米乳、纳米粒和复合制剂等,具有给药方便、增加药物溶解吸收、提高药物生物利用度及缓释效果显著等优点。结论两类泊洛沙姆是疏水药物新剂型研究的理想载体之一,尤其在中药难溶性有效成分给药系统研究中应用前景广阔。     

多西紫杉醇纳米制剂的研究进展

摘 要多西紫杉醇作为一种高效广谱的抗肿瘤药,临床上用于不同类型实体瘤的治疗,但是水溶性差限制了其制剂的开发。纳米载药系统在提高难溶性药物溶解度、靶向给药、减少药物不良反应等方面极具发展前景。因此,采用纳米载体传递多西紫杉醇的研究受到广泛关注。本文综述了近几年来多西紫杉醇纳米制剂的研究进展,包括脂质体、纳米粒、生物共轭物、聚合物胶束、纳米乳、纳米囊、树枝状聚合物等,以期为新型纳米制剂的开发和应用提供参考。     

Solubility enhancers for oral drug delivery

With recent progress in high throughput screening of potential therapeutic agents, the number of poorly water-soluble drug candidates has risen sharply and formulating for poorly water-soluble compounds for oral delivery now presents one of the most frequent and greatest challenges to scientists in the pharmaceutical industry. Many new drugs and potential therapeutic compounds under investigation possess high lipophilicity, poor water solubility, and low oral bioavailability. Furthermore, development of improved oral dosage forms for currently marketed drugs can also enhance their therapeutic value. Oral delivery systems designed for poorly water-soluble drugs include micelles with surfactants, microemulsions, self-emulsifying/microemulsifying drug delivery systems (SEDDS/SMEDDS), solid dispersions, microspheres and cyclodextrin inclusion complexes. These delivery systems have been shown to enhance oral bioavailability and therapeutic effects of poorly water-soluble drugs mainly by improving the poor solubility. As a consequence of extensive research, various oral delivery systems for poorly water-soluble agents are being developed in clinical phases worldwide. New formulation technologies and multidisciplinary expertise may lead to development of advanced and effective oral drug delivery systems applicable to a wide range of poorly water-soluble drugs in the near future.     

Formulation design for poorly water-soluble drugs based on biopharmaceutics classification system: basic approaches and practical applications

The poor oral bioavailability arising from poor aqueous solubility should make drug research and development more difficult. Various approaches have been developed with a focus on enhancement of the solubility, dissolution rate, and oral bioavailability of poorly water-soluble drugs. To complete development works within a limited amount of time, the establishment of a suitable formulation strategy should be a key consideration for the pharmaceutical development of poorly water-soluble drugs. In this article, viable formulation options are reviewed on the basis of the biopharmaceutics classification system of drug substances. The article describes the basic approaches for poorly water-soluble drugs, such as crystal modification, micronization, amorphization, self-emulsification, cyclodextrin complexation, and pH modification. Literature-based examples of the formulation options for poorly water-soluble compounds and their practical application to marketed products are also provided. Classification of drug candidates based on their biopharmaceutical properties can provide an indication of the difficulty of drug development works. A better understanding of the physicochemical and biopharmaceutical properties of drug substances and the limitations of each delivery option should lead to efficient formulation development for poorly water-soluble drugs.     

Oral formulation strategies to improve solubility of poorly water-soluble drugs

INTRODUCTION: In the past two decades, there has been a spiraling increase in the complexity and specificity of drug-receptor targets. It is possible to design drugs for these diverse targets with advances in combinatorial chemistry and high throughput screening. Unfortunately, but not entirely unexpectedly, these advances have been accompanied by an increase in the structural complexity and a decrease in the solubility of the active pharmaceutical ingredient. Therefore, the importance of formulation strategies to improve the solubility of poorly water-soluble drugs is inevitable, thus making it crucial to understand and explore the recent trends. AREAS COVERED: Drug delivery systems (DDS), such as solid dispersions, soluble complexes, self-emulsifying drug delivery systems (SEDDS), nanocrystals and mesoporous inorganic carriers, are discussed briefly in this review, along with examples of marketed products. This article provides the reader with a concise overview of currently relevant formulation strategies and proposes anticipated future trends. EXPERT OPINION: Today, the pharmaceutical industry has at its disposal a series of reliable and scalable formulation strategies for poorly soluble drugs. However, due to a lack of understanding of the basic physical chemistry behind these strategies, formulation development is still driven by trial and error.     

Oral formulation strategies to improve solubility of poorly water-soluble drugs

Introduction: In the past two decades, there has been a spiraling increase in the complexity and specificity of drug–receptor targets. It is possible to design drugs for these diverse targets with advances in combinatorial chemistry and high throughput screening. Unfortunately, but not entirely unexpectedly, these advances have been accompanied by an increase in the structural complexity and a decrease in the solubility of the active pharmaceutical ingredient. Therefore, the importance of formulation strategies to improve the solubility of poorly water-soluble drugs is inevitable, thus making it crucial to understand and explore the recent trends.

Areas covered: Drug delivery systems (DDS), such as solid dispersions, soluble complexes, self-emulsifying drug delivery systems (SEDDS), nanocrystals and mesoporous inorganic carriers, are discussed briefly in this review, along with examples of marketed products. This article provides the reader with a concise overview of currently relevant formulation strategies and proposes anticipated future trends.

Expert opinion: Today, the pharmaceutical industry has at its disposal a series of reliable and scalable formulation strategies for poorly soluble drugs. However, due to a lack of understanding of the basic physical chemistry behind these strategies, formulation development is still driven by trial and error.     

Insoluble drug delivery strategies: review of recent advances and business prospects

The emerging trends in the combinatorial chemistry and drug design have led to the development of drug candidates with greater lipophilicity, high molecular weight and poor water solubility. Majority of the failures in new drug development have been attributed to poor water solubility of the drug. Issues associated with poor solubility can lead to low bioavailability resulting in suboptimal drug delivery. About 40% of drugs with market approval and nearly 90% of molecules in the discovery pipeline are poorly water-soluble. With the advent of various insoluble drug delivery technologies, the challenge to formulate poorly water soluble drugs could be achieved. Numerous drugs associated with poor solubility and low bioavailabilities have been formulated into successful drug products. Several marketed drugs were reformulated to improve efficacy, safety and patient compliance. In order to gain marketing exclusivity and patent protection for such products, revitalization of poorly soluble drugs using insoluble drug delivery technologies have been successfully adopted by many pharmaceutical companies. This review covers the recent advances in the field of insoluble drug delivery and business prospects.KEY WORDS: Bioavailability, Cocrystals, Solubility, Inclusion complexation, Nanoparticles, Self-emulsifying formulations, Proliposomes     

共无定形给药系统研究进展

共无定形药物是将活性药物成分和其他药物或辅料等小分子固体组分混合形成的一种二元单相无定形固体分散体给药系统。作为一种新颖的药物传递系统，共无定形药物可能改善水难溶性药物的溶解度和口服生物利用度问题，为仿制药物和复方药物的开发提供了新的策略和思路。近年来，共无定形药物在学术和制药工业领域受到广泛关注。本文综述了共无定形药物的载体材料的筛选、制备方法、物理稳定机制，以及体外溶出性能和体内吸收情况，并对共无定形药物的未来发展前景进行了展望。     

Transforming Lipid-Based Oral Drug Delivery Systems into Solid Dosage Forms: An Overview of Solid Carriers, Physicochemical Properties, and Biopharmaceutical Performance

The diversity of lipid excipients available commercially has enabled versatile formulation design of lipid-based drug delivery systems for enhancing the oral absorption of poorly water-soluble drugs, such as emulsions, microemulsions, micelles, liposomes, niosomes and various self-emulsifying systems. The transformation of liquid lipid-based systems into solid dosage forms has been investigated for several decades, and has recently become a core subject of pharmaceutical research as solidification is regarded as viable means for stabilising lipid colloidal systems while eliminating stringent processing requirements associated with liquid systems. This review describes the types of pharmaceutical grade excipients (silica nanoparticle/microparticle, polysaccharide, polymer and protein-based materials) used as solid carriers and the current state of knowledge on the liquid-to-solid conversion approaches. Details are primarily focused on the solid-state physicochemical properties and redispersion capacity of various dry lipid-based formulations, and how these relate to the in vitro drug release and solubilisation, lipid carrier digestion and cell permeation performances. Numerous in vivo proof-of-concept studies are presented to highlight the viability of these dry lipid-based formulations. This review is significant in directing future research work in fostering translation of dry lipid-based formulations into clinical applications.     

Development of solid dispersion lipid nanoparticles for improving skin delivery

Applications of poorly water-soluble drugs in skin delivery pose several challenges to pharmaceutical formulation. This research originally developed solid lipid nanoparticles (SLNs) packaging a modified core of a solid dispersion (SD) in the lipid matrix to modulate the skin release patterns. Curcumin (CUR) was selected as the poorly water-soluble drug applied in the formulation. The designed system, so-called solid dispersion lipid nanoparticles (SD-SLNs), was fabricated by incorporating a solidifying SD or a non-solidifying SD into the core of the SLNs by ultrasonication. Release studies illustrated an important enhancement in the drug release of the proposed system compared to pure CUR and SLN formulations without the presence of SD as the modified core, which indicated the positive effect of the combined colloidal method of SD and SLNs. The physicochemical properties of the SD-SLN systems were also elucidated using powder X-ray diffraction, Fourier transform infrared spectroscopy, and particle size analysis. The drug was found to change to an amorphous state without any molecular interactions along with a marked particle size reduction. This work demonstrated the strong potential of applying a novel SD-SLN system for the skin delivery of a drug with poor water solubility.     

Coaxial electrospray formulations for improving oral absorption of a poorly water-soluble drug

Development of oral dosage forms containing poorly water-soluble drugs is a major challenge in the pharmaceutical industry. This paper describes the use of coaxial electrospray deposition as a promising formulation technology for oral delivery of poorly water-soluble drugs. The technology produced core-shell particles composed of griseofulvin and poly(methacrylic acid-co-methyl methacrylate) (Eudragit L-100), with a diameter of around 1 μm. The drug phase was in an amorphous state when the griseofulvin core was coated with the Eudragit L-100 shell. The in vitro dissolution and in vivo oral absorption studies revealed that the core-shell formulation significantly improved dissolution and absorption behaviors, presumably because of a reduction in particle size, improvement in dispersity, and amorphization. Results demonstrated that coaxial electrospray deposition possesses great potential as novel formulation technology for enhancing oral absorption of poorly water-soluble drugs.