Lucia Lopez-Vidal, Mariano Tinti, Maria Elisa Melian, Lucila Canton, Matias Lorenzutti, Laureano Schofs, Maria Lina Formica, Alejandro J Paredes, Sergio Sanchez Bruni, Nicolas Litterio, Ricardo Faccio, Santiago Daniel Palma, Juan Pablo Real
{"title":"In vivo pharmacokinetic study and PBPK modeling: Comparison between 3D-printed nanocrystals and solid dispersions.","authors":"Lucia Lopez-Vidal, Mariano Tinti, Maria Elisa Melian, Lucila Canton, Matias Lorenzutti, Laureano Schofs, Maria Lina Formica, Alejandro J Paredes, Sergio Sanchez Bruni, Nicolas Litterio, Ricardo Faccio, Santiago Daniel Palma, Juan Pablo Real","doi":"10.1016/j.ijpharm.2024.125063","DOIUrl":null,"url":null,"abstract":"<p><p>The solubility of drugs remains one of the most challenging aspects of formulation development. Several technologies exist to enhance the properties of poorly soluble drugs, with nanocrystal (NC) and solid dispersion (SD) technologies being among the most important. This work compared NCs and SDs under identical conditions using albendazole as a model drug and 3D printing technology as the delivery method. SDs were initially prepared and characterized, and then compared to the NCs system. Techniques such as TGA, DSC, XRD, FTIR, SEM, and Raman spectroscopy were employed to assess the solid-state properties and formulation homogeneity. Solubility and dissolution profiles were evaluated under simulated gastric and intestinal conditions. An in vivo pharmacokinetic study in dogs compared 3D-printed formulations (NC-3D and SD-3D) with a control group treated with the pure drug (ABZ-C) was carry out. A PBPK model was developed also in dogs to further analyse the results. While no statistically significant differences were observed in the in vitro dissolution profiles in 0.1 N HCl, differences emerged in precipitation time and solubility at intestinal pH (6.8). The pharmacokinetic study revealed improvements in the pharmacokinetic profile of both systems compared to the control, as expected. Between the NCs and the SD, the NC system demonstrated significantly superior pharmacokinetic parameters of interest. The PBPK model helped explain the differences observed in the in vivo study. The results suggest that nanocrystal technology is more effective at enhancing the in vivo performance of Class II drugs, at least when using albendazole as the model drug.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"125063"},"PeriodicalIF":5.3000,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Pharmaceutics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ijpharm.2024.125063","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
The solubility of drugs remains one of the most challenging aspects of formulation development. Several technologies exist to enhance the properties of poorly soluble drugs, with nanocrystal (NC) and solid dispersion (SD) technologies being among the most important. This work compared NCs and SDs under identical conditions using albendazole as a model drug and 3D printing technology as the delivery method. SDs were initially prepared and characterized, and then compared to the NCs system. Techniques such as TGA, DSC, XRD, FTIR, SEM, and Raman spectroscopy were employed to assess the solid-state properties and formulation homogeneity. Solubility and dissolution profiles were evaluated under simulated gastric and intestinal conditions. An in vivo pharmacokinetic study in dogs compared 3D-printed formulations (NC-3D and SD-3D) with a control group treated with the pure drug (ABZ-C) was carry out. A PBPK model was developed also in dogs to further analyse the results. While no statistically significant differences were observed in the in vitro dissolution profiles in 0.1 N HCl, differences emerged in precipitation time and solubility at intestinal pH (6.8). The pharmacokinetic study revealed improvements in the pharmacokinetic profile of both systems compared to the control, as expected. Between the NCs and the SD, the NC system demonstrated significantly superior pharmacokinetic parameters of interest. The PBPK model helped explain the differences observed in the in vivo study. The results suggest that nanocrystal technology is more effective at enhancing the in vivo performance of Class II drugs, at least when using albendazole as the model drug.
期刊介绍:
The International Journal of Pharmaceutics is the third most cited journal in the "Pharmacy & Pharmacology" category out of 366 journals, being the true home for pharmaceutical scientists concerned with the physical, chemical and biological properties of devices and delivery systems for drugs, vaccines and biologicals, including their design, manufacture and evaluation. This includes evaluation of the properties of drugs, excipients such as surfactants and polymers and novel materials. The journal has special sections on pharmaceutical nanotechnology and personalized medicines, and publishes research papers, reviews, commentaries and letters to the editor as well as special issues.