Effect of formulation variables on design, in vitro evaluation of valsartan SNEDDS and estimation of its antioxidant effect in adrenaline-induced acute myocardial infarction in rats.
Valsartan is a specific angiotensin II antagonist used for the treatment of hypertension. It suffers from low aqueous solubility and high variability in its absorption after oral administration. The aim of this study was to improve the dissolution and thereby the bioavailability of Valsartan through the development of self nano-emulsifying drug delivery systems. Four ternary phase diagrams were constructed to identify the self-emulsification region of Capmul® MCM, Labrafil® M1944, Capryol™ 90 and Labrafac® PG together with Cremophore® RH 40 and Transcutol™ HP as oil, surfactant and co-surfactant, respectively. The effect of oil type, oil and surfactant concentration on droplet size and in vitro Valsartan dissolution were studied. The protective effect of the optimum formula F5 in adrenaline-induced oxidative stress in rats during myocardial infarction was determined. Formula F5 exhibited globule size of (13.95 nm) with 76.07% ± 1.10 of Valsartan dissolved after five minutes compared to Disartan 80 mg capsules (13.43%). Results revealed a significant reduction (p < 0.05) in serum aspartate transaminase, creatine kinase myocardial band and malondialdehyde levels, while a significant increase (p < 0.05) in serum glutathione in F5. Therefore, self nano-emulsifying drug delivery systems could be considered as a promising approach to improve the dissolution and thereby the bioavailability of Valsartan.
a Pharmaceutics and Industrial Pharmacy Department, Faculty of Pharmacy , Cairo University , Cairo , Egypt.
Maha M
MM
Amin
a Pharmaceutics and Industrial Pharmacy Department, Faculty of Pharmacy , Cairo University , Cairo , Egypt.
Omaima N
ON
El Gazayerly
b Pharmaceutics and Industrial Pharmacy Department, Faculty of Pharmacy , October 6 University , Sixth of October City , Egypt , and.
Nabaweya A
NA
Abd El-Gawad
b Pharmaceutics and Industrial Pharmacy Department, Faculty of Pharmacy , October 6 University , Sixth of October City , Egypt , and.
Shady M
SM
Abd El-Halim
c Department of Pharmacology , National Research Center , Cairo , Egypt.
Sally A
SA
El-Awdan
D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods; D004655:Emulsions / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology*; D005079:Excipients / Q000737:chemistry; D008297:Male; D009203:Myocardial Infarction / Q000139:chemically induced* / Q000188:drug therapy*; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D000068756:Valsartan / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*
D000975:Antioxidants; D004655:Emulsions; D005079:Excipients; D013501:Surface-Active Agents; D000068756:Valsartan; D004837:Epinephrine
Angiotensin II antagonist; BCS class II; oxidative stress; ternary phase diagram