title: Systematic development of optimized SNEDDS of artemether with improved biopharmaceutical and antimalarial potential.
abstract: The current studies entail systematic development of self-nanoemulsifying drug delivery systems (SNEDDS) containing medium-chain triglycerides (MCTs) and long-chain triglycerides (LCTs) for augmenting the biopharmaceutical performance of artemether. Equilibrium solubility and pseudoternary phase diagram studies facilitated selection of Captex 355 and Ethyl oleate as MCTs and LCTs, and Cremophor RH 40 and Tween 80 as surfactants, while Transcutol HP as cosolvent for formulating the SNEDDS. Systematic optimization was performed employing the Box-Behnken design taking concentrations of lipid, surfactant and cosolvent as the critical material attributes (CMAs), while evaluating for globule size, emulsification time, dissolution efficiency and permeation as the critical quality attributes (CQAs). In situ single pass intestinal perfusion (SPIP) studies in Wistar rats substantiated significant augmentation in the absorption (5- to 6-fold) and permeation (4- to 5-fold) parameters from the optimized MCT and LCT-SNEDDS vis-à-vis the pure drug. In vivo pharmacodynamic studies in Plasmodium berghi infected laca mice exhibited superior reduction in the levels of percent parasitemia, SGOT, SGPT and bilirubin, followed by higher survival rate of the animals by optimized MCT-SNEDDS followed by LCT-SNEDDS vis-à-vis the pure drug, which was subsequently ratified through histopathological examination of liver tissues. Overall, the studies construed successful development of the optimized SNEDDS of artemether with distinctly improved biopharmaceutical and antimalarial potential.
authors.affiliation: a UGC Centre of Advanced Studies, University Institute of Pharmaceutical Sciences, Panjab University , Chandigarh , India.
authors.forename: Chandra Bhushan
authors.initials: CB
authors.lastname: Tripathi
authors.affiliation: a UGC Centre of Advanced Studies, University Institute of Pharmaceutical Sciences, Panjab University , Chandigarh , India.
authors.forename: Sarwar
authors.initials: S
authors.lastname: Beg
authors.affiliation: b UGC- Centre of Excellence in Applications of Nanomaterials, Nanoparticles and Nanocomposites (Biomedical Sciences), Panjab University , Chandigarh , India.
authors.forename: Ripandeep
authors.initials: R
authors.lastname: Kaur
authors.affiliation: c Department of Microbiology , Panjab University , Chandigarh , India , and.
authors.forename: Geeta
authors.initials: G
authors.lastname: Shukla
authors.affiliation: d Division of Pharmaceutics , PDM College of Pharmacy, Sarai Aurangabad, Bahadurgarh , Haryana , India.
authors.forename: Shantanu
authors.initials: S
authors.lastname: Bandopadhyay
authors.affiliation: a UGC Centre of Advanced Studies, University Institute of Pharmaceutical Sciences, Panjab University , Chandigarh , India.|b UGC- Centre of Excellence in Applications of Nanomaterials, Nanoparticles and Nanocomposites (Biomedical Sciences), Panjab University , Chandigarh , India.
authors.forename: Bhupinder
authors.initials: B
authors.lastname: Singh
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000737:chemistry*; D000077549:Artemether; D037621:Artemisinins / Q000008:administration & dosage / Q000737:chemistry*; D001702:Biopharmaceutics / Q000379:methods; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems / Q000379:methods; D004655:Emulsions / Q000008:administration & dosage / Q000737:chemistry; D005260:Female; D007408:Intestinal Absorption; D008055:Lipids; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D010316:Particle Size; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D015996:Survival Rate; D014280:Triglycerides / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004655:Emulsions; D008055:Lipids; D013501:Surface-Active Agents; D014280:Triglycerides; D000077549:Artemether
keywords: Absorption; nanoemulsion; parasitemia; quality by design; solubility