Birla Institute of Technology and Science (BITS) Pilani, Hyderabad Campus, Shameerpet, Hyderabad, Telangana, India.
Natco Research Center, Natco Pharma Limited, Sanath Nagar, Hyderabad, Telangana, India.
Pharm Dev Technol. 2024 Jun;29(5):530-540. doi: 10.1080/10837450.2024.2353314. Epub 2024 May 28.
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).
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.
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. pharmacokinetic study in Wistar rats showed that C and AUC of PCZ-NCS increased by 2.58- and 2.64-fold compared to the marketed formulation.
PCZ-NCS formulation presents a viable approach for enhancing the oral bioavailability of PCZ.
泊沙康唑（PCZ）是一种抗真菌药物，通过抑制羊毛甾醇 14α-去甲基酶发挥作用。它是生物制药分类系统 II 类药物，其生物利用度受到较差的水溶性限制。本研究旨在通过制备纳米晶固体分散体（NCS）来提高 PCZ 的口服生物利用度。
通过沉淀和高压匀浆结合冷冻干燥法制备 PCZ-NCS。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。
发现含有 0.2%Eudragit S100 和 0.2%SLS 的优化 NCS 配方可提供平均粒径为 73.31±4.7nm、多分散指数为 0.23±0.03 的颗粒。扫描电子显微镜显示制备出了均匀且圆形的颗粒。差示扫描量热法和 X 射线衍射证实了 NCS 的结晶性质。纳米化使 PCZ 的饱和溶解度比纯药物提高了约 18 倍。体内溶解研究表明，PCZ-NCS 在最初 10 分钟内有 93%的 PCZ 溶解。在 Wistar 大鼠中的药代动力学研究表明，与市售制剂相比，PCZ-NCS 的 C 和 AUC 增加了 2.58-2.64 倍。
PCZ-NCS 制剂为提高 PCZ 的口服生物利用度提供了一种可行的方法。
