Enhancing Solubility of a BCS Class II Drug- Itraconazole by Developing and Optimizing Solid Lipid Nanoparticles using a Central Composite Design.

Q2 Pharmacology, Toxicology and Pharmaceutics

Pharmaceutical nanotechnology Pub Date : 2025-01-21 DOI:10.2174/0122117385341583250119054309

Irfan A Mohammed, Sriramakamal Jonnalagadda

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引用次数: 0

Abstract

Background: Itraconazole (ICZ) has been approved by the FDA to treat many fungal infections including, blastomycosis, histoplasmosis, and aspergillosis. ICZ can be also used as prophylaxis in the population who are at high risk for developing systemic fungal infections, such as HIV patients, and chemotherapy patients.

Aim: However, since ICZ is a BCS Class II drug that has low solubility and high permeability, leads to low oral bioavailability. In addition, the absorption of ICZ from commercial oral dosage forms is highly affected by food intake and pH.

Objective: The current study aimed to develop, optimize, and characterize ICZ-loaded solid lipid nanoparticles (ICZ-SLNs) using a Central Composite Design for improved solubility and extendedrelease profile.

Methods: ICZ-SLNs were optimized based on physicochemical characteristics. ICZ-SLNs were also evaluated for differential scanning calorimetry (DSC), in-vitro release, lyophilization, transmission electron microscopy (TEM), and physicochemical stability at refrigerated and room temperatures for three months.

Results: The optimized ICZ-SLNs formulation showed particle size, polydispersity index, zeta potential, drug content, and entrapment efficiency of 335.6±8.0 nm, 0.25±0.02, -23.8±0.5 mV, 98.3±2.5%, and 99.5±1.5%, respectively. ICZ-SLN dispersions showed extended-release profiles for ICZ compared to the control solution over 24 h. The absence of the endothermic melting drug peak of the lyophilized formulation indicated that the drug was converted to its amorphous form inside the solid matrix. In addition, TEM studies showed spherical shape nanoparticles. Moreover, the optimized ICZ-SLN formulation was stable at both tested storage conditions.

Conclusion: The current ICZ formulation could exhibit improved oral bioavailability with better therapeutic outcomes during the treatment of systemic fungal infections.

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利用中心复合设计开发和优化固体脂质纳米颗粒以提高BCS二类药物伊曲康唑的溶解度。

背景：伊曲康唑（ICZ）已被FDA批准用于治疗多种真菌感染，包括芽孢菌病、组织胞浆菌病和曲霉病。ICZ也可用于发生全身性真菌感染的高危人群，如HIV患者和化疗患者。目的：然而，由于ICZ是BCS II类药物，具有低溶解度和高通透性，导致口服生物利用度低。此外，商业口服剂型中ICZ的吸收受到食物摄入量和ph的高度影响。目的：本研究旨在利用中心复合设计来开发、优化和表征装载ICZ的固体脂质纳米颗粒（ICZ- slns），以改善其溶解度和缓释特性。方法：基于理化特性对icz - sln进行优化。对icz - sln进行了差示扫描量热法（DSC）、体外释放、冻干、透射电镜（TEM）和冷藏和室温下3个月的理化稳定性评估。结果：优化后的ICZ-SLNs粒径为335.6±8.0 nm，多分散性指数为0.25±0.02，zeta电位为-23.8±0.5 mV，药物含量为98.3±2.5%，包封效率为99.5±1.5%。与对照溶液相比，ICZ- sln分散体在24 h内表现出ICZ的缓释特征。冻干制剂中没有吸热融化峰，表明药物在固体基质内转化为无定形。此外，透射电镜研究显示球形纳米颗粒。此外，优化后的ICZ-SLN配方在两种测试条件下都是稳定的。结论：该制剂在治疗全身性真菌感染中具有较好的口服生物利用度和治疗效果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmaceutical nanotechnology Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science

CiteScore

4.20

自引率

0.00%

发文量

期刊介绍： Pharmaceutical Nanotechnology publishes original manuscripts, full-length/mini reviews, thematic issues, rapid technical notes and commentaries that provide insights into the synthesis, characterisation and pharmaceutical (or diagnostic) application of materials at the nanoscale. The nanoscale is defined as a size range of below 1 µm. Scientific findings related to micro and macro systems with functionality residing within features defined at the nanoscale are also within the scope of the journal. Manuscripts detailing the synthesis, exhaustive characterisation, biological evaluation, clinical testing and/ or toxicological assessment of nanomaterials are of particular interest to the journal’s readership. Articles should be self contained, centred around a well founded hypothesis and should aim to showcase the pharmaceutical/ diagnostic implications of the nanotechnology approach. Manuscripts should aim, wherever possible, to demonstrate the in vivo impact of any nanotechnological intervention. As reducing a material to the nanoscale is capable of fundamentally altering the material’s properties, the journal’s readership is particularly interested in new characterisation techniques and the advanced properties that originate from this size reduction. Both bottom up and top down approaches to the realisation of nanomaterials lie within the scope of the journal.