A Self-nanoemulsifying Drug Delivery System for Enhancing the Oral Bioavailability of Candesartan Cilexetil: Ex Vivo and In Vivo Evaluation.

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ID: 18788
2019
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Abstract
The drug delivery of candesartan cilexetil encounters an obstacle of low absolute oral bioavailability which is attributed mainly to its low aqueous solubility and efflux by intestinal P-glycoprotein (P-gp) transporters. However, the extent of P-gp contribution in the reduced oral bioavailability of candesartan cilexetil is not clear. In this study, a previously developed candesartan cilexetil-loaded self-nanoemulsifying drug delivery system (SNEDDS) was evaluated for its ability to increase the drug oral bioavailability via the inhibition of intestinal P-gp transporters. Despite the developed SNEDDS showing P-gp inhibition activity, P-gp-mediated efflux was found to have a minor role in the reduced oral bioavailability of candesartan cilexetil. On the other hand, the high surfactant concentration used in SNEDDS formulation represents a major challenge toward their widespread application especially for chronically administered drugs. The designed acute and subacute toxicity studies revealed that the degree of intestinal mucosal damage decreases as the treatment period increases. The latter observation was attributed to the reversibility of surfactant-induced mucosal damage. Thus, the developed SNEDDS could be considered as a promising delivery system for enhancing the oral bioavailability of chronically administered drugs.
Reference Key
aboulfotouh2019ajournal Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors AboulFotouh, Khaled;Allam, Ayat A;El-Badry, Mahmoud;El-Sayed, Ahmed M;
Journal journal of pharmaceutical sciences
Year 2019
DOI
S0022-3549(19)30439-3
URL
Keywords Keywords not found

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