title: Development of solid self-nanoemulsifying granules (SSNEGs) of ondansetron hydrochloride with enhanced bioavailability potential.
abstract: The current work aims to prepare the solid self-nanoemulsifying granules (SSNEGs) of ondansetron hydrochloride (ONH) to enhance its oral bioavailability by improving its aqueous solubility and facilitating its absorption though lymphatic pathways. Preformulation studies including screening of excipients for solubility and pseudoternary phase diagrams suggested the suitability of Capmul MCM as lipid, Labrasol as surfactant, and Tween 20 as cosurfactant for preparation of self-emulsifying formulations. Preliminary composition of the SNEDDS formulations were selected from the phase diagrams and subjected to thermodynamic stability studies and dispersibility tests. The prepared liquid SNEDDS formulations were characterized for viscosity, refractive index, droplet size and zeta potential. The TEM study confirmed the formation of nanoemulsion following dilution of liquid SNEDDS. The optimized liquid SNEDDS were transformed into free flowing granules by adsorption on the porous carriers like Sylysia (350, 550, and 730) and Neusilin™ US2. Solid state characterization employing the FTIR, DSC and powder XRD studies indicated lack of any significant interaction of drug with the lipidic and emulsifying excipients, and porous carriers. In vitro drug release studies indicated faster solubilization of the drug by optimized SSNEGs (over 80% within 30 min) vis-à-vis the pure drug (only 35% within 30 min). In vivo pharmacokinetic studies in Wistar rats observed significant increase in C(max) (3.01-fold) and AUC (5.34-fold) using SSNEGs compared to pure drug, whereas no significant difference (p>0.1) was observed with the liquid SNEDDS. Thus, the present studies ratify the bioavailability enhancement potential of SSNEGs of ONH prepared using porous carriers.
authors.affiliation: Department of Pharmaceutics, Roland Institute of Pharmaceutical Sciences, Berhampur, Orissa, India.
authors.forename: Sarwar
authors.initials: S
authors.lastname: Beg
authors.forename: Sidharth Sankar
authors.initials: SS
authors.lastname: Jena
authors.forename: Ch Niranjan
authors.initials: ChN
authors.lastname: Patra
authors.forename: Mohammad
authors.initials: M
authors.lastname: Rizwan
authors.forename: Suryakanta
authors.initials: S
authors.lastname: Swain
authors.forename: J
authors.initials: J
authors.lastname: Sruti
authors.forename: M E Bhanoji
authors.initials: ME
authors.lastname: Rao
authors.forename: Bhupinder
authors.initials: B
authors.lastname: Singh
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D000932:Antiemetics / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D004655:Emulsions; D005079:Excipients; D005260:Female; D008099:Liver / Q000378:metabolism; D008208:Lymphatic System / Q000378:metabolism; D008297:Male; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D017294:Ondansetron / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D012031:Refractometry; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013501:Surface-Active Agents; D013816:Thermodynamics; D014783:Viscosity; D014961:X-Ray Diffraction
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000932:Antiemetics; D004655:Emulsions; D005079:Excipients; D013501:Surface-Active Agents; D017294:Ondansetron