推进口服给药的纳米战略:多孔硅颗粒和环糊精包封技术促进难溶性药物的溶解。

IF 5.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Hennie Marie Johnsen, Werner Filtvedt, Jo Klaveness, Marianne Hiorth
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引用次数: 0

摘要

由于生物利用率低,口服新型活性药物成分(API)的开发常常面临挑战。基于纳米颗粒的给药系统和环糊精(CD)封装技术通过提高原料药的溶解度或溶解速率,提供了前景广阔的解决方案。多孔硅纳米粒子已显示出将无定形形式的原料药封装在孔隙中的潜力,与晶体形式的原料药相比,可提高溶出率。利用离心化学气相沉积(cCVD)技术,开发出一种新的合成方法,避免了昂贵而繁琐的硅晶片材料合成过程。在此,我们评估了各种 cCVD 硅颗粒提高模型药物塞来昔布 (CEL)、苯妥英 (PHT)、格列齐特 (GRI)、双氯芬酸 (DCF) 和萘普生 (NAP) 溶出率的能力。我们的研究结果表明,在 pH 值为 7.4 或 pH 值为 2.0 的条件下,与游离原料药相比,使用 cCVD Si 粒子配制的所有受测原料药的溶出率都有所提高。装载后,颗粒特性基本保持不变,并使用差示扫描量热法(DSC)对装载的原料药的固态进行了评估。溶解动力学受颗粒特性、质量负载和原料药特性的影响。在 cCVD Si 粒子中加入 CD-CEL、-GRI 和 -DCF 复合物显示出进一步提高溶出率的潜力,这是对这种组合的首次研究报道。总之,cCVD 硅颗粒有望提高溶解性差的药物的溶解速率,这可能是由于无定形或析出形式的缘故。载入 CD 药物复合物后,药物溶出率进一步提高,从而为优化药物生物利用度提供了可行的策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Nano-strategies for advancing oral drug delivery: Porous silicon particles and cyclodextrin encapsulation for enhanced dissolution of poorly soluble drugs.

Development of novel active pharmaceutical ingredients (API) for oral use often face challenges due to low bioavailability. Nanoparticle-based drug delivery systems and cyclodextrin (CD) encapsulation offer promising solutions by enhancing API solubility or dissolution rates. Porous silicon nanoparticles have shown potential to encapsulate APIs in their amorphous form within pores, improving dissolution rates compared to crystalline counterparts. A novel synthesis approach, circumventing the expensive and tedious Si wafer material synthesis, has been developed using centrifugal Chemical Vapor Deposition (cCVD). Herein, various cCVD Si particles were evaluated for their ability to enhance the dissolution rate of the model drugs celecoxib (CEL), phenytoin (PHT), griseofulvin (GRI), diclofenac (DCF), and naproxen (NAP). Our findings demonstrate increased dissolution rates of all tested APIs when formulated with cCVD Si particles, compared to free API in pH 7.4 or pH 2.0. Particle characteristics were largely retained after loading, and the solid state of the loaded APIs were evaluated using Differential Scanning Calorimetry (DSC). Dissolution kinetics were influenced by the particle properties, mass loading and API characteristics. Loading of CD-CEL, -GRI and -DCF complexes into the cCVD Si particles showed a potential for further enhanced dissolution rates, representing the first reported investigation of this combination. In conclusion, the cCVD Si particles are promising for improving the dissolution rate of poorly soluble drugs, potentially due to precipitation of amorphous or metastable forms. Further enhancements were observed upon loading CD-drug complexes, thereby offering promising strategies for optimizing drug bioavailability.

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来源期刊
CiteScore
10.70
自引率
8.60%
发文量
951
审稿时长
72 days
期刊介绍: The International Journal of Pharmaceutics is the third most cited journal in the "Pharmacy & Pharmacology" category out of 366 journals, being the true home for pharmaceutical scientists concerned with the physical, chemical and biological properties of devices and delivery systems for drugs, vaccines and biologicals, including their design, manufacture and evaluation. This includes evaluation of the properties of drugs, excipients such as surfactants and polymers and novel materials. The journal has special sections on pharmaceutical nanotechnology and personalized medicines, and publishes research papers, reviews, commentaries and letters to the editor as well as special issues.
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