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A Self-Nanoemulsifying Drug Delivery System for Enhancing the Oral Bioavailability of Candesartan Cilexetil: Ex Vivo and In Vivo Evaluation.
J Pharm Sci. 2019 11; 108(11):3599-3608.JP

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.

Authors+Show Affiliations

Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt. Electronic address: elbadry@aun.edu.eg.Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31348934

Citation

AboulFotouh, Khaled, et al. "A Self-Nanoemulsifying Drug Delivery System for Enhancing the Oral Bioavailability of Candesartan Cilexetil: Ex Vivo and in Vivo Evaluation." Journal of Pharmaceutical Sciences, vol. 108, no. 11, 2019, pp. 3599-3608.
AboulFotouh K, Allam AA, El-Badry M, et al. A Self-Nanoemulsifying Drug Delivery System for Enhancing the Oral Bioavailability of Candesartan Cilexetil: Ex Vivo and In Vivo Evaluation. J Pharm Sci. 2019;108(11):3599-3608.
AboulFotouh, K., Allam, A. A., El-Badry, M., & El-Sayed, A. M. (2019). A Self-Nanoemulsifying Drug Delivery System for Enhancing the Oral Bioavailability of Candesartan Cilexetil: Ex Vivo and In Vivo Evaluation. Journal of Pharmaceutical Sciences, 108(11), 3599-3608. https://doi.org/10.1016/j.xphs.2019.07.004
AboulFotouh K, et al. A Self-Nanoemulsifying Drug Delivery System for Enhancing the Oral Bioavailability of Candesartan Cilexetil: Ex Vivo and in Vivo Evaluation. J Pharm Sci. 2019;108(11):3599-3608. PubMed PMID: 31348934.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A Self-Nanoemulsifying Drug Delivery System for Enhancing the Oral Bioavailability of Candesartan Cilexetil: Ex Vivo and In Vivo Evaluation. AU - AboulFotouh,Khaled, AU - Allam,Ayat A, AU - El-Badry,Mahmoud, AU - El-Sayed,Ahmed M, Y1 - 2019/07/23/ PY - 2018/11/10/received PY - 2019/06/05/revised PY - 2019/07/17/accepted PY - 2019/7/28/pubmed PY - 2020/9/9/medline PY - 2019/7/27/entrez KW - MTT (PubChem CID: (64965) KW - bioavailability KW - candesartan (PubChem CID: 2541) KW - candesartan cilexetil (PubChem CID: 2540) KW - peppermint oil (PubChem CID: 6850741) KW - permeability KW - toxicity SP - 3599 EP - 3608 JF - Journal of pharmaceutical sciences JO - J Pharm Sci VL - 108 IS - 11 N2 - 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. SN - 1520-6017 UR - https://www.unboundmedicine.com/medline/citation/31348934/A_Self_Nanoemulsifying_Drug_Delivery_System_for_Enhancing_the_Oral_Bioavailability_of_Candesartan_Cilexetil:_Ex_Vivo_and_In_Vivo_Evaluation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-3549(19)30439-3 DB - PRIME DP - Unbound Medicine ER -