In Vitro Lipolysis Data Does Not Adequately Predict the In Vivo Performance of Lipid-Based Drug Delivery Systems Containing Fenofibrate
| Autor: | Katharina Richter, Nicky Thomas, Thomas Rades, René Holm, Anette Müllertz, Thomas Bæk Pedersen |
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| Přispěvatelé: | Thomas, Nicky, Richter, Katharina, Pedersen, Thomas B, Holm, René, Müllertz, Anette, Rades, Thomas |
| Rok vydání: | 2014 |
| Předmět: |
Male
Drug Swine Chemistry Pharmaceutical Lipolysis supersaturation media_common.quotation_subject Pharmaceutical Science Pharmacology Excipients lipids Drug Delivery Systems Fenofibrate Suspensions In vivo medicine Animals in vitro/in vivo correlation Intestinal Mucosa Hypolipidemic Agents media_common Supersaturation Chemistry in vitro ipolysis Lipids In vitro SNEDDS suspensions Gastric Mucosa Solubilization super-SNEDDS Drug delivery Swine Miniature Research Article medicine.drug |
| Zdroj: | The AAPS Journal. 16:539-549 |
| ISSN: | 1550-7416 |
| DOI: | 10.1208/s12248-014-9589-4 |
| Popis: | The present study investigated the utility of in vitro lipolysis performance indicators drug solubilization and maximum supersaturation ratio (SRM) for their predictive use for the in vivo performance in a minipig model. The commercial Lipanthyl formulation and a series of LbDDS based on identical self-nanoemulsifying drug delivery systems (SNEDDS) containing 200 mg of fenofibrate, either dissolved or suspended, were subjected to combined gastric (pH 2) and intestinal (pH 6.5) in vitro lipolysis. Based on the solubilization profiles and SRM the rank-order SNEDDS (75% drug load) > super-SNEDDS (150% drug load, dissolved) = SNEDDS suspension (150% drug load, partially suspended) > Lipanthyl was established, with an increased likelihood of drug precipitation above SRM > 3. The in vitro performance, however, was not reproduced in vivo in a minipig model as the mean plasma concentration over time curves of all LbDDS were comparable, independent of the initial physical state of the drug. There was no correlation between the area under the solubilization-time curves (AUC in vitro ) of the intestinal step and the AUC in vivo . The study suggests careful interpretation of in vitro performance criteria and revision of LbDDS optimization towards increased solubilization. |
| Databáze: | OpenAIRE |
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