ABSTRACT
The objective of this study is to develop nanostructured lipid formulations of Compritol for the delivery of mebendazole. The formulations were prepared with Compritol 888 ATO, squalane, and Pluronic F68. Nine batches with different amounts of modifier, squalane, and drug were prepared. The formulations were characterized by evaluating particle size, morphology, and zeta potential. The thermal properties of the formulations were analyzed by differential scanning calorimetry (DSC). The encapsulation efficiency of each formulation and the drug release rates from each formulation were quantified by UPLC. The particles were spherical and had median particle sizes between 300 and 600 nm (50th percentile). A linear relationship was observed between Compritol/squalane composition and the melting point of the mixture. The DSC scans of the formulations revealed some recrystallization of the drug from the formulations, and the amount of recrystallization correlated with the amount of squalane in the formulation. Approximately, 70% efficiency of encapsulation was observed in the formulations with 30% (w/w) squalane, and these formulations also had faster dissolution rates compared to the other formulations. Overall, the formulations with 30% squalane are the preferred formulation for future testing.
Subject(s)
Drug Carriers , Fatty Acids , Mebendazole/administration & dosage , Nanoparticles , Squalene/analogs & derivatives , Tubulin Modulators/administration & dosage , Calorimetry, Differential Scanning , Drug Carriers/chemistry , Drug Liberation , Fatty Acids/chemistry , Mebendazole/pharmacokinetics , Microscopy, Electron, Scanning , Nanoparticles/chemistry , Particle Size , Poloxamer/chemistry , Squalene/chemistry , Transition Temperature , Tubulin Modulators/pharmacokineticsABSTRACT
OBJECTIVE: The goal of this study is to develop an ultra-high performance liquid chromatographic method for the quantitative determination of artemisinin at very low concentrations using selective ion mass spectroscopic detection. MATERIALS AND METHODS: Separation was conducted using a C4 100 mm× 2.1 mm column, and the mobile phase consisted of an isocratic two-component system consisting of 60% of a 0.1% aqueous solution of formic acid and 40% acetonitrile at a flow rate of 0.4 ml/min. The drug was detected by means of an electrospray mass spectrometer with selective ion monitoring of the [M-H2O+H](+) with m/z of 265.3 in positive ion mode. RESULTS: The calibration curves of artemisinin obtained from the UPLC/MS system were linear in the three ranges analyzed, with a correlation coefficient of no less than 0.9996 for all sets of standards. The peak tailing factor for all measurements were ≤1.7. The method proved to have good repeatability and linearity. DISCUSSION: The described analytical method reached a LOQ of 0.010 µg/ml with an isocratic system and enables an analysis rate of 20 samples per hour. The linearity of the standards was excellent for all sets of standards analyzed. CONCLUSION: The method presented in this study provides a rapid and suitable means for the determination of artemisinin at very low concentrations. This is especially significant when performing dissolution studies where, due to the low solubility of artemisinin, a method that can measure the drug at nanogram levels is necessary.
