{"title":"Development of posaconazole nanocrystalline solid dispersion: preparation, characterization and <i>in vivo</i> evaluation.","authors":"Ranga Goud Rayapolu, Balvant Yadav, Shashank S Apte, Venkata Vamsi Krishna Venuganti","doi":"10.1080/10837450.2024.2353314","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>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).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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. <i>In vivo</i> pharmacokinetic study in Wistar rats showed that C<sub>max</sub> and AUC<sub>total</sub> of PCZ-NCS increased by 2.58- and 2.64-fold compared to the marketed formulation.</p><p><strong>Conclusion: </strong>PCZ-NCS formulation presents a viable approach for enhancing the oral bioavailability of PCZ.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"530-540"},"PeriodicalIF":2.6000,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmaceutical Development and Technology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/10837450.2024.2353314","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/5/28 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
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.
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.