Development of posaconazole nanocrystalline solid dispersion: preparation, characterization and in vivo evaluation.

IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Ranga Goud Rayapolu, Balvant Yadav, Shashank S Apte, Venkata Vamsi Krishna Venuganti
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引用次数: 0

Abstract

Objective: Posaconazole (PCZ) is an antifungal drug, which acts by inhibiting the lanosterol-14α-demethylase enzyme. It is a biopharmaceutical classification system class II drug with its bioavailability being limited by poor aqueous solubility. The aim of this study was to improve the oral bioavailability of PCZ by preparing nanocrystalline solid dispersion (NCS).

Methods: PCZ-NCS was prepared by a combination of precipitation and high-pressure homogenization followed by freeze-drying. Several different surfactants and polymers were screened to produce NCS with smaller particle size and higher stability.

Results: The optimized NCS formulation containing 0.2% Eudragit S100 and 0.2% SLS was found to provide the average particle size of 73.31 ± 4.7 nm with a polydispersity index of 0.23 ± 0.03. Scanning electron microscopy revealed the preparation of homogeneous and rounded particles. Differential scanning calorimetry and X-ray diffraction confirmed crystalline nature of NCS. Nanonization increased the saturation solubility of PCZ by about 18-fold in comparison with the neat drug. Intrinsic dissolution study showed 93% dissolution of PCZ within the first 10 min. In vivo pharmacokinetic study in Wistar rats showed that Cmax and AUCtotal of PCZ-NCS increased by 2.58- and 2.64-fold compared to the marketed formulation.

Conclusion: PCZ-NCS formulation presents a viable approach for enhancing the oral bioavailability of PCZ.

泊沙康唑纳米晶体固体分散体的开发:制备、表征和体内评价。
目的:泊沙康唑(PCZ)是一种抗真菌药物:泊沙康唑(PCZ)是一种抗真菌药物,通过抑制羊毛甾醇-14α-脱甲基酶发挥作用。它属于生物制药分类系统 II 类药物,由于水溶性差,其生物利用度受到限制。本研究旨在通过制备纳米结晶固体分散体(NCS)来提高 PCZ 的口服生物利用度:方法:采用沉淀和高压均质相结合的方法制备 PCZ-NCS,然后进行冷冻干燥。筛选了几种不同的表面活性剂和聚合物,以制备粒径更小、稳定性更高的 NCS:结果:含有 0.2% Eudragit S100 和 0.2% SLS 的优化 NCS 配方的平均粒径为 73.31 ± 4.7 nm,多分散指数为 0.23 ± 0.03。扫描电子显微镜显示制备出了均匀的圆形颗粒。差示扫描量热法和 X 射线衍射证实了 NCS 的结晶性质。与纯药物相比,纳米化使 PCZ 的饱和溶解度提高了约 18 倍。内在溶解度研究表明,PCZ 在最初 10 分钟内的溶解度为 93%。在 Wistar 大鼠体内进行的药代动力学研究表明,与市售制剂相比,PCZ-NCS 的 Cmax 和 AUC 总值分别增加了 2.58 倍和 2.64 倍:PCZ-NCS 制剂是提高 PCZ 口服生物利用度的一种可行方法。
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来源期刊
CiteScore
5.90
自引率
2.90%
发文量
82
审稿时长
1 months
期刊介绍: Pharmaceutical Development & Technology publishes research on the design, development, manufacture, and evaluation of conventional and novel drug delivery systems, emphasizing practical solutions and applications to theoretical and research-based problems. The journal aims to publish significant, innovative and original research to advance the frontiers of pharmaceutical development and technology. Through original articles, reviews (where prior discussion with the EIC is encouraged), short reports, book reviews and technical notes, Pharmaceutical Development & Technology covers aspects such as: -Preformulation and pharmaceutical formulation studies -Pharmaceutical materials selection and characterization -Pharmaceutical process development, engineering, scale-up and industrialisation, and process validation -QbD in the form a risk assessment and DoE driven approaches -Design of dosage forms and drug delivery systems -Emerging pharmaceutical formulation and drug delivery technologies with a focus on personalised therapies -Drug delivery systems research and quality improvement -Pharmaceutical regulatory affairs This journal will not consider for publication manuscripts focusing purely on clinical evaluations, botanicals, or animal models.
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