In Vitro-In Vivo Correlations of Carbamazepine Nanodispersions for Application in Formulation Development
| Autor: | Michael M. Puppolo, Justin R. Hughey, Zachary N. Warnken, Iris Duarte, Susan A. Jansen‐Varnum |
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| Rok vydání: | 2017 |
| Předmět: |
Polymers
Chemistry Pharmaceutical Pharmaceutical Science Biological Availability 02 engineering and technology Pharmacology 030226 pharmacology & pharmacy Permeability 03 medical and health sciences Mice 0302 clinical medicine Dogs Pharmacokinetics Polymethacrylic Acids medicine Animals Dissolution testing In vitro in vivo Solubility Dissolution Chromatography Chemistry Carbamazepine 021001 nanoscience & nanotechnology Bioavailability Spray drying Nanoparticles 0210 nano-technology medicine.drug |
| Zdroj: | Journal of pharmaceutical sciences. 107(1) |
| ISSN: | 1520-6017 |
| Popis: | During formulation development, efficiently integrating in vitro dissolution testing can significantly improve one's ability to estimate in vivo performance and aide in the selection of premier drug candidates. The concept of in vitro-in vivo relationship/correlation has garnered significant attention from pharmaceutical scientists to predict expected bioavailability characteristics for drug substances and products. The present work illustrates a comparative evaluation of in vitro tests to access crystalline carbamazepine and various types of amorphous and crystalline dispersions of carbamazepine and Eudragit® L100 produced by spray drying, including a membrane-permeation dissolution methodology and nonsink dissolution. To establish the best model, parameters such as pH, membrane constitution, and dissolution media composition were investigated. The in vitro results were compared against in vivo mice pharmacokinetic studies and qualitatively, the membrane-permeation dissolution methodology correlated well with in vivo. Various correlations were performed in order to evaluate the optimal model for characterizing the relationship. Results exhibited a coefficient of determination (R2) values of 0.90 and 1.00, depicting a linear relationship of the data in comparison. Therefore, for the current formulation system (drug/polymer/technique), membrane-permeation dissolution can guide formulation development and potentially reduce the number of animal and clinical pharmacokinetic studies required. |
| Databáze: | OpenAIRE |
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