AAPS PharmSciTech最新文献

The Role of Amphiphilic Compounds in Nasal Nanoparticles 两亲化合物在鼻腔纳米颗粒中的作用

IF 3.4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2024-11-19 DOI: 10.1208/s12249-024-03000-8

Thinh To Quoc, Krisztina Bíró, Ágota Pető, Dóra Kósa, Ádám Haimhoffer, István Lekli, Ádám Pallér, István Bak, Alexandra Gyöngyösi, Pálma Fehér, Ildikó Bácskay, Zoltán Ujhelyi

Nasal medications hold significant importance and are widely utilized due to their numerous advantageous properties, offering a compelling route for both local and systemic therapeutic effects. Nowadays, the development of nasal particles under 1 micrometer is in the focus of much scientific research. In our experiments, the use of innovative nanotechnology to increase the effectiveness of the active substance was of paramount importance. Our aim was to create solid nanoparticles that enable targeted and effective delivery of the active ingredient into the body. The innovation of this experimental series lies not only in highlighting the importance of amphiphilic compounds in enhancing penetration, but also in the fact that while most nasally administered formulations are in liquid form, our formulation is solid. Liquid formulations frequently suffer from the disadvantage of possible leakage during administration, which can reduce the bioavailability of the active ingredient. In our experiments we created novel drug delivery systems of finely divided powders, which, thanks to the penetration enhancers, can be successfully administered. These enhancers facilitate the swift disintegration and penetration of the particles through the membrane. This represents a new direction in nasal drug delivery methods. The results of our trials are promising in the development of innovative pharmaceutical products and outline the role of amphiphilic compounds in more efficient utilization and targeted application of active substances. According to our results it can be concluded that this innovative approach not only addresses the common issues associated with liquid nasal formulations but also paves the way for more stable and effective delivery methods. The use of finely divided powders for nasal delivery, enabled by penetration enhancers, represents a major breakthrough in the field, providing a dependable alternative to conventional liquid formulations and ensuring improved therapeutic results.

Graphical Abstract

鼻腔用药具有重要意义，并因其众多的优势特性而被广泛使用，为局部和全身治疗效果提供了令人信服的途径。如今，开发 1 微米以下的鼻腔微粒已成为科学研究的焦点。在我们的实验中，利用创新纳米技术提高活性物质的有效性至关重要。我们的目标是创造出固体纳米粒子，以便有针对性地将活性成分有效输送到体内。这一系列实验的创新之处不仅在于强调了两亲化合物在增强渗透性方面的重要性，还在于大多数鼻腔给药制剂都是液态的，而我们的制剂是固态的。液体制剂经常存在给药过程中可能渗漏的缺点，这会降低活性成分的生物利用率。在我们的实验中，我们创造了由细小粉末组成的新型给药系统，由于使用了渗透促进剂，这种系统可以成功给药。这些增强剂有助于颗粒迅速崩解并穿透薄膜。这代表了鼻腔给药方法的新方向。我们的试验结果为创新药物产品的开发带来了希望，并勾勒出了两亲化合物在更有效地利用和有针对性地应用活性物质方面的作用。根据我们的结果，可以得出这样的结论：这种创新方法不仅解决了与鼻腔液体制剂相关的常见问题，还为更稳定、更有效的给药方法铺平了道路。在渗透促进剂的作用下，使用细分粉末进行鼻腔给药是该领域的一项重大突破，为传统的液体制剂提供了可靠的替代品，并确保了更好的治疗效果。

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引用次数: 0

Predicting the Thermodynamic Solubility and Stability of Co-crystals and Eutectics of Febuxostat by using a Thermodynamic Model involving Flory Huggins Interaction Parameter 利用涉及弗洛里-赫金斯相互作用参数的热力学模型预测非布索坦共晶体和共晶的热力学溶解度和稳定性

IF 3.4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2024-11-19 DOI: 10.1208/s12249-024-02979-4

Moksh Jagia, Arvind K. Bansal, Sarsvatkumar Patel

A method is presented for determining the thermodynamic (equilibrium) solubility of a drug in coformer for the non-covalent derivative (NCD) systems i.e. eutectics/co-crystals. The method is based on a thermodynamic model to calculate the Gibbs energy change ∆G_CC associated with forming a drug-coformer NCD system. This model includes contributions from heat capacity differences between the mixed and unmixed components, breaking up of the solid drug and coformer lattice structure, and drug ─ coformer mixing. Calculation of ∆G_CC from thermal analysis data is demonstrated, and the equilibrium drug solubility in coformer is represented by minima of plots of ∆G_CC versus the dissolved drug fraction (f₁). Eight (8) coformer molecules, namely, 1-hydroxy 2-naphthoic acid (1H-2NPH), 4-hydroxy benzoic acid (4-HBA), salicylic acid (SLC), 4-amino salicylic acid (4-ASA), 5-nitro isophthalic acid (5N-IPH), pyrazinamide (PZD), isonicotinamide (ISNCT), and picolinamide (PICO) were used for the formation of NCDs of a highly water insoluble drug febuxostat (FXT). The importance of heat capacity and interaction parameter in determining the solubility behavior of drug-coformer in the formed NCDs was discussed. Further, ∆G_CC for FXT in selected NCDs were plotted as a function of composition and temperature to determine the thermodynamic stability over the range of room temperature to formulation melting. It was concluded that the thermodynamic model can reasonably predict the maximum stable drug loading in a multi-crystalline system at a particular temperature, and serve as a complementary screening tool in determining the best stoichiometric ratio of the drug and coformer in terms of solubility and thermodynamic stability.

Graphical Abstract

本文提出了一种方法，用于确定药物在非共价衍生物（NCD）系统（即共晶/共晶体）中的热力学（平衡）溶解度。该方法基于一个热力学模型来计算与形成药物-共形物 NCD 系统相关的吉布斯能量变化 ∆GCC。该模型包括混合成分和未混合成分之间的热容量差异、固体药物和共形体晶格结构的破裂以及药物 - 共形体混合。演示了根据热分析数据计算 ∆GCC 的过程，并通过 ∆GCC 与溶解药物组分 (f1) 的最小值图来表示药物在共聚物中的平衡溶解度。八（8）种共聚物分子，即 1-hydroxy 2-naphthoic acid (1H-2NPH)、4-hydroxy benzoic acid (4-HBA)、salicylic acid (SLC)、4-amino salicylic acid (4-ASA)、5-硝基异酞酸 (5N-IPH)、吡嗪酰胺 (PZD)、异烟酰胺 (ISNCT) 和吡啶酰胺 (PICO) 被用于形成高度不溶于水的药物非布索坦 (FXT) 的 NCD。讨论了热容量和相互作用参数在决定药物-配体在所形成的 NCD 中的溶解度行为方面的重要性。此外，还绘制了选定 NCD 中 FXT 的 ∆GCC 与成分和温度的函数关系图，以确定从室温到制剂熔化的热力学稳定性。结论是，该热力学模型可以合理预测多晶体体系在特定温度下的最大稳定药物载量，并可作为辅助筛选工具，从溶解度和热力学稳定性的角度确定药物和共配体的最佳化学计量比。

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引用次数: 0

The Role of Phase Separation and Local Mobility in the Stabilization of a Lyophilized IgG2 Formulation 相分离和局部流动性在稳定冻干 IgG2 制剂中的作用

IF 3.4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2024-11-19 DOI: 10.1208/s12249-024-02984-7

Ashley Lay-Fortenbery, Ryan E. Holcomb, Charles S. Henry, Mark Cornell Manning, Eric J. Munson

The utility of employing solid-state NMR (SSNMR) to assess parameters governing the stability of a lyophilized IgG2 protein was the focus of the present work. Specifically, the interaction between the sugar stabilizer (sucrose) and protein component was measured using SSNMR and compared to physical and chemical stability data obtained from thermally stressed samples. ¹H T₁ and ¹H T_1⍴ relaxation times were measured by SSMNR for 5 different formulation conditions, and the resultant values were used to examine local mobility and phase separation, respectively. From the SSNMR measurements, it was found local mobility decreased as the sucrose to protein weight ratio increased. The decrease in local mobility corresponded to an increase in storage stability (both chemical and physical) of the lyophilized solids up to a critical weight ratio of sucrose to protein. Additionally, ¹H T_1⍴ measurements obtained on formulations having higher protein to sucrose weight ratios indicated phase separation of the protein and sucrose phases was occurring, at least on a small scale. Along with an increase in local mobility, phase separation in these specific formulations is thought to have played a role in their decreased storage stability in the solid state.

Graphical Abstract

本研究的重点是利用固态核磁共振（SSNMR）评估影响冻干 IgG2 蛋白稳定性的参数。具体来说，使用 SSNMR 测量了糖稳定剂（蔗糖）和蛋白质成分之间的相互作用，并与热应力样品获得的物理和化学稳定性数据进行了比较。通过 SSMNR 测量了 5 种不同配方条件下的 1H T1 和 1H T1⍴ 弛豫时间，所得数值分别用于检测局部流动性和相分离。SSNMNR 测量结果表明，随着蔗糖与蛋白质重量比的增加，局部流动性降低。在蔗糖与蛋白质的重量比达到临界值时，局部迁移率的降低与冻干固体储存稳定性（化学和物理）的提高相对应。此外，对蛋白质与蔗糖重量比更高的配方进行的 1H T1⍴ 测量表明，至少在小范围内，蛋白质相和蔗糖相正在发生相分离。随着局部流动性的增加，这些特定配方中的相分离被认为是导致其固态储存稳定性降低的原因之一。

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引用次数: 0

Correction: Croscarmellose Sodium as Pelletization Aid in Extrusion-Spheronization 更正：在挤压-乳化过程中作为造粒助剂的卡司卡莫司钠

IF 3.4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2024-11-12 DOI: 10.1208/s12249-024-02989-2

Finn Siebel, Peter Kleinebudde

引用次数: 0

Chitosan-Based Nanoformulations: Preclinical Investigations, Theranostic Advancements, and Clinical Trial Prospects for Targeting Diverse Pathologies 壳聚糖基纳米制剂：针对不同病症的临床前研究、治疗学进展和临床试验前景。

IF 3.4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2024-11-05 DOI: 10.1208/s12249-024-02948-x

Seema Yadav, Abhishek Singh, Narahari N. Palei, Prateek Pathak, Amita Verma, Jagat Pal Yadav

Chitosan, a biocompatible and biodegradable polymer, has attracted significant interest in the development of nanoformulations for targeted drug delivery and therapeutic applications. The versatility of chitosan lies in its modifiable functional groups, which can be tailored to diverse applications. Nanoparticles derived from chitosan and its derivatives typically exhibit a positive surface charge and mucoadhesive properties, enabling them to adhere to negatively charged biological membranes and gradually release therapeutic agents. This comprehensive review investigates the manifold roles of chitosan-based nanocarriers, ranging from preclinical research to theranostic applications and clinical trials, across a spectrum of diseases, including neurological disorders, cardiovascular diseases, cancer, wound healing, gastrointestinal disorders, and pulmonary diseases. The exploration starts with an overview of preclinical studies, emphasizing the potential of chitosan-based nanoformulations in optimizing drug delivery, improving therapeutic outcomes, and mitigating adverse effects in various disease categories. Advancements in theranostic applications of chitosan-based nanoformulations highlight their adaptability to diverse diseases. As these nanoformulations progress toward clinical translation, this review also addresses the regulatory challenges associated with their development and proposes potential solutions.

Graphical Abstract

壳聚糖是一种生物相容性和可生物降解的聚合物，在开发用于靶向给药和治疗应用的纳米制剂方面引起了极大的兴趣。壳聚糖的多功能性在于其可修饰的官能团，可根据不同的应用进行定制。壳聚糖及其衍生物制成的纳米颗粒通常具有正表面电荷和粘液粘附特性，使其能够粘附在带负电荷的生物膜上，并逐渐释放治疗药物。这篇综合性综述探讨了壳聚糖基纳米载体的多种作用，从临床前研究到治疗应用和临床试验，涉及多种疾病，包括神经系统疾病、心血管疾病、癌症、伤口愈合、胃肠道疾病和肺部疾病。探讨从临床前研究概述开始，强调基于壳聚糖的纳米制剂在优化药物输送、改善治疗效果和减轻各类疾病的不良反应方面的潜力。基于壳聚糖的纳米制剂在治疗学应用方面取得的进展突显了其对各种疾病的适应性。随着这些纳米制剂逐步应用于临床，本综述还探讨了与其开发相关的监管挑战，并提出了潜在的解决方案。

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引用次数: 0

The Neoteric Paradigm of Biomolecule-Functionalized Albumin-Based Targeted Cancer Therapeutics 基于生物分子功能化白蛋白的癌症靶向治疗新范例。

IF 3.4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2024-11-05 DOI: 10.1208/s12249-024-02977-6

Swati Gunjkar, Ujala Gupta, Rahul Nair, Priti Paul, Mayur Aalhate, Srushti Mahajan, Indrani Maji, Manish K. Chourasia, Santosh Kumar Guru, Pankaj Kumar Singh

Albumin is a nature-derived, versatile protein carrier, that has been explored extensively by researchers for anticancer drug delivery due to its role in enhancing drug stability, solubility, circulation time, targeting capabilities, and overall therapeutic efficacy. Albumin nanoparticles possess inherent biocompatibility, biodegradability, and passive tumor-targeting ability due to the enhanced permeability and retention effect. However, non-specific accumulation of cytotoxic agents in healthy tissues remains a challenge. In this paper, the functionalization of albumin nanoparticles using various biomolecules including antibodies, nucleic acids, proteins and peptides, vitamins, chondroitin sulfate, hyaluronic acid, and lactobionic acid have been discussed which enables specific recognition and binding to cancer cells. Furthermore, we highlight the supremacy of such a targeted approach in tumor-specific drug delivery, minimization of off-target effects, potential improvement in therapeutic efficacy, cellular internalization, reduced side effects, and better clinical outcomes. This review centers on how they have revolutionized the field of biomedical research and tuned into an excellent targeted approach. In conclusion, this review highlights in detail the role of albumin as a nanocarrier for tumor-targeted delivery using biomolecules as ligands.

Graphical Abstract

白蛋白是一种来源于自然界的多功能蛋白质载体，由于其在增强药物稳定性、溶解性、循环时间、靶向能力和整体疗效方面的作用，研究人员在抗癌药物递送方面进行了广泛的探索。白蛋白纳米粒子具有固有的生物相容性、生物可降解性以及因渗透性和滞留效应增强而产生的被动肿瘤靶向能力。然而，细胞毒剂在健康组织中的非特异性蓄积仍然是一个挑战。本文讨论了利用各种生物大分子（包括抗体、核酸、蛋白质和肽、维生素、硫酸软骨素、透明质酸和乳糖酸）对白蛋白纳米颗粒进行功能化，从而实现对癌细胞的特异性识别和结合。此外，我们还强调了这种靶向方法在肿瘤特异性给药、最大限度地减少脱靶效应、潜在的疗效改善、细胞内化、减少副作用和更好的临床效果等方面的优越性。本综述的中心内容是它们如何彻底改变了生物医学研究领域，并调整为一种出色的靶向方法。总之，本综述详细强调了白蛋白作为一种纳米载体，以生物分子为配体进行肿瘤靶向递送的作用。

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引用次数: 0

Magnesium Stearate Fatty Acid Composition, Lubrication Performance and Tablet Properties 硬脂酸镁脂肪酸组成、润滑性能和片剂性能。

IF 3.4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2024-11-05 DOI: 10.1208/s12249-024-02980-x

Natalia Veronica, Paul Wan Sia Heng, Celine Valeria Liew

Magnesium stearate (MgSt) is a common tablet lubricant. As variations in MgSt properties are known to influence tablet attributes, the impact of MgSt fatty acid composition, particularly the significance of the stearate and palmitate contents, and its effects on tablet properties warrant further investigation. This study investigated the effect of MgSt with different stearate and palmitate contents but comparable physical properties (e.g. particle size, crystallinity, specific surface area and morphology) on lubrication performance and resulting tablet quality attributes, including mechanical strength, disintegratability and drug release. The influence of MgSt concentration and blending duration on the resulting tablet properties was also examined. Tablets produced using the lower stearate content MgSt had slightly higher tensile strength. The effect of MgSt stearate content was more apparent in the disintegration time and drug release, whereby MgSt of lower stearate content resulted in tablets with longer disintegration time and slower drug release. The lower stearate content also resulted in a lower lubrication performance, leading to a lesser reduction in tablet ejection force. As expected, a longer blending time of the tablet formulation blend with MgSt yielded tablets with reduced tensile strength, shorter disintegration time and slower drug release. Tablets with higher MgSt concentration showed a greater reduction in tensile strength, longer disintegration time and faster drug release. The study findings reinforced observations by other researchers and provided a better understanding of the fatty acid composition effects of MgSt on lubrication performance and the resulting tablet properties.

Graphical Abstract

硬脂酸镁（MgSt）是一种常见的片剂润滑剂。众所周知，硬脂酸镁特性的变化会影响片剂属性，因此有必要进一步研究硬脂酸镁脂肪酸组成的影响，特别是硬脂酸和棕榈酸酯含量的重要性及其对片剂特性的影响。本研究调查了硬脂酸盐和棕榈酸盐含量不同但物理性质（如粒度、结晶度、比表面积和形态）相当的 MgSt 对润滑性能和由此产生的片剂质量属性（包括机械强度、崩解性和药物释放）的影响。此外，还研究了 MgSt 浓度和混合时间对片剂性能的影响。使用硬脂酸镁含量较低的硬脂酸镁生产的片剂拉伸强度略高。硬脂酸镁含量对崩解时间和药物释放的影响更为明显，硬脂酸镁含量较低的片剂崩解时间较长，药物释放较慢。硬脂酸镁含量越低，润滑性能越差，导致药片弹射力降低。正如预期的那样，片剂配方与硬脂酸镁的混合时间越长，片剂的拉伸强度越低，崩解时间越短，药物释放越慢。MgSt 浓度较高的片剂抗张强度降低幅度更大，崩解时间更长，药物释放更快。研究结果加强了其他研究人员的观察结果，使人们更好地了解了 MgSt 脂肪酸成分对润滑性能和由此产生的片剂特性的影响。

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引用次数: 0

Vesicular Carriers for Improved Oral Anticoagulation Competence of Rivaroxaban: In Vitro and In Vivo Investigation 提高利伐沙班口服抗凝能力的囊状载体：体外和体内研究

IF 3.4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2024-11-05 DOI: 10.1208/s12249-024-02962-z

Samar H. Faheim, Gamal M. El Maghraby, Amal A. Sultan

Rivaroxaban is an anticoagulant for avoidance and therapy of thromboembolic disorders. Unfortunately, oral bioavailability of rivaroxaban is compromised with dose increments. Accordingly, the aim was to test nano-vesicular lipid systems for improved oral anticoagulation activity of rivaroxaban. Rivaroxaban loaded niosomes, bilosomes and spanlastic formulations were prepared. The prepared systems were assessed in terms of particle size, zeta potential, transition electron microscopic features (TEM), entrapment efficiency, in-vitro drug release, and in-vivo anticoagulation performance in rats. The prepared vesicular systems exposed spherical negatively charged vesicles with mean particle size values between 136.6 nm to 387.9 nm depending on the composition. Rivaroxaban was efficiently entrapped in the vesicular systems with entrapment efficiency values ranging from 92.4% to 94.0%. Rivaroxaban underwent sustained release from the fabricated vesicular systems. The in vivo performance of the tested preparation revealed significant enhancement of the anticoagulation parameters. This was manifested from the prolonged clotting time, and prothrombin time. Moreover, the cut tails of the examined rats receiving the formulated nano-systems exposed a lengthy tail bleeding time compared to those receiving the un-processed rivaroxaban aqueous dispersion. In Conclusion, niosomes, bilosomes and spanlastic nano-dispersions have a potential to overwhelm the oral anticoagulation efficiency of rivaroxaban with spanlastic ranked as best.

Graphical Abstract

利伐沙班是一种抗凝剂，用于避免和治疗血栓栓塞性疾病。遗憾的是，随着剂量的增加，利伐沙班的口服生物利用度会受到影响。因此，我们的目的是测试纳米囊脂质系统，以提高利伐沙班的口服抗凝活性。研究人员制备了利伐沙班负载的niosomes、bilosomes和spanlastic制剂。对所制备的系统进行了粒度、ZETA电位、过渡电子显微镜特征（TEM）、夹持效率、体外药物释放和大鼠体内抗凝性能等方面的评估。所制备的囊泡系统呈带负电荷的球形囊泡，平均粒径在 136.6 纳米到 387.9 纳米之间，具体取决于成分。利伐沙班被有效地夹持在囊泡系统中，夹持效率值在 92.4% 到 94.0% 之间。利伐沙班可从制成的囊泡系统中持续释放。测试制剂的体内性能表明，抗凝参数显著提高。这表现在凝血时间和凝血酶原时间的延长上。此外，与接受未经加工的利伐沙班水分散体的大鼠相比，接受配制的纳米系统的大鼠切尾出血时间较长。总之，niosomes、bilosomes 和 spanlastic 纳米分散体有可能提高利伐沙班的口服抗凝效率，其中 spanlastic 的效果最好。

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引用次数: 0

Correction: Investigations on the Impacts of Drugs or Excipients with Different Physicochemical and Compaction Properties on the Disintegration Behavior of Kollidon®SR-Based Binary Controlled Release Matrix Tablets 更正：基于 Kollidon®SR 的二元控释基质片剂的崩解行为：不同理化性质和压实性质的药物或辅料的影响研究。

IF 3.4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2024-11-05 DOI: 10.1208/s12249-024-02981-w

Wasfy M. Obeidat, Shadi F. Gharaibeh

引用次数: 0

Formononetin-Loaded Self-Microemulsion Drug Delivery Systems for Improved Solubility and Oral Bioavailability: Fabrication, Characterization, In Vitro and In Vivo Evaluation 提高溶解度和口服生物利用度的福莫西汀负载型自微乳化给药系统：制造、表征、体外和体内评估。

IF 3.4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2024-11-01 DOI: 10.1208/s12249-024-02975-8

Zhihui Zou, Yuanyuan Xue, Michael Adu-Frimpong, ChengWei Wang, Zhou Jin, Ying Xu, Jiangnan Yu, Ximing Xu, Yuan Zhu

This study aimed to construct a self-microemulsion drug delivery system (SMEDDS) for Formononetin (FMN) to improve its solubility and bioavailability while combining the nanocrystals (NCs) technology. The SMEDDS prescription composition was optimized with a pseudo-three-phase diagram, followed by a series of in vitro and in vivo evaluations of the selected optimal prescriptions. FMN-NCs loaded SMEDDS showed a homogeneous spherical shape in the Transmission electron microscope and the particle size was measured as (20.65 ± 1.42) nm. The in vitro cumulative release rate in each dissolution medium within 30 min was higher than 80%, much higher than that of FMN (6%) and FMN-NCs (40%); Cellular experiments confirm that the formulation has a high safety profile and significantly promotes cellular uptake. The results of pharmacokinetics and intestinal absorption in rats showed that the relative bioavailability of FMN-NCs and FMN-NCs loaded SMEDDS were (154.80 ± 3.76)% and (557.73 ± 32.88)%, respectively, and both of them significantly increased the rate and extent of absorption of the drug in intestinal segments. FMN-NCs loaded SMEDDS significantly enhanced the solubility and bioavailability of FMN.

Graphical Abstract

本研究旨在构建福莫西汀（FMN）的自微乳给药系统（SMEDDS），以提高其溶解度和生物利用度，同时结合纳米晶体（NCs）技术。通过伪三相图优化了 SMEDDS 的处方组成，随后对选定的最佳处方进行了一系列体外和体内评估。在透射电子显微镜下，负载 FMN-NCs 的 SMEDDS 呈均匀球形，粒径为（20.65 ± 1.42）纳米。30分钟内在各溶解介质中的体外累积释放率均高于80%，远高于FMN（6%）和FMN-NCs（40%）；细胞实验证实该制剂具有较高的安全性，并能显著促进细胞吸收。大鼠的药代动力学和肠道吸收结果表明，FMN-NCs 和 FMN-NCs 负载 SMEDDS 的相对生物利用度分别为（154.80 ± 3.76）% 和（557.73 ± 32.88）%，两者都能显著提高药物在肠段的吸收率和吸收程度。FMN-NCs 负载 SMEDDS 能显著提高 FMN 的溶解度和生物利用度。

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引用次数: 0