title: Solvent injection-lyophilization of tert-butyl alcohol/water cosolvent systems for the preparation of drug-loaded solid lipid nanoparticles.
abstract: A simple procedure involving solvent injection-lyophilization (SIL) was used to prepare solid lipid nanoparticles (SLNs). A tert-butyl alcohol (t-BA) solution containing lipids was injected into a stirred aqueous solution containing lyoprotectants to form SLNs dispersed in a t-BA/water cosolvent system. The t-BA/water cosolvent SLN dispersion was subsequently lyophilized to obtain a dry product which, upon rehydration, formed an aqueous dispersion of spherical SLNs with a size under 200 nm. A lipophilic drug, cinnarizine, was dissolved in t-BA at a drug-to-lipid mass ratio of 1:20 and almost 100% of the drug was entrapped in the formed SLNs following the SIL process. Likewise, hydrophilic 5-fluorouracil, after being solubilized in t-BA through forming anhydrous reverse micelles, could be entrapped in SLNs with an encapsulation efficiency up to 15.6%. Differential scanning calorimetry and small angle X-ray scattering analysis proved that the lipids in the formed SLNs were in a stable beta-form, and there was no recrystallization expulsion of drugs during storage. In contrast to the conventional solvent injection method, the SIL procedure was not time-consuming and no relatively high-temperature evaporation was needed to remove organic solvents. Moreover, the efficiency of the lyophilization was markedly enhanced due to use of the t-BA/water cosolvent system. Thus, the SIL procedure was found to be an efficient method for preparing stable drug-loaded SLNs.
authors.affiliation: Department of Pharmacy, Jining Medical College, Sunshine City, Shandong Province, 276826, China. twangcn@yahoo.com
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.forename: Yingying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Wancui
authors.initials: W
authors.lastname: Shen
authors.forename: Xingmei
authors.initials: X
authors.lastname: Gao
authors.forename: Tiefu
authors.initials: T
authors.lastname: Li
mesh_terms: D002152:Calorimetry, Differential Scanning; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding; D004355:Drug Stability; D008055:Lipids / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D053838:Scattering, Small Angle; D012997:Solvents / Q000737:chemistry*; D013696:Temperature; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction; D020002:tert-Butyl Alcohol / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D008055:Lipids; D004364:Pharmaceutical Preparations; D012997:Solvents; D014867:Water; D020002:tert-Butyl Alcohol