Supercritical Fluid Chromatography of Drugs: Parallel Factor Analysis for Column Testing in a Wide Range of Operational Conditions.

Retention mechanisms involved in supercritical fluid chromatography (SFC) are influenced by interdependent parameters (temperature, pressure, chemistry of the mobile phase, and nature of the stationary phase), a complexity which makes the selection of a proper stationary phase for a given separation a challenging step. For the first time in SFC studies, Parallel Factor Analysis (PARAFAC) was employed to evaluate the chromatographic behavior of eight different stationary phases in a wide range of chromatographic conditions (temperature, pressure, and gradient elution composition). Design of Experiment was used to optimize experiments involving 14 pharmaceutical compounds present in biological and/or environmental samples and with dissimilar physicochemical properties. The results showed the superiority of PARAFAC for the analysis of the three-way (column × drug × condition) data array over unfolding the multiway array to matrices and performing several classical principal component analyses. Thanks to the PARAFAC components, similarity in columns' function, chromatographic trend of drugs, and correlation between separation conditions could be simply depicted: columns were grouped according to their H-bonding forces, while gradient composition was dominating for condition classification. Also, the number of drugs could be efficiently reduced for columns classification as some of them exhibited a similar behavior, as shown by hierarchical clustering based on PARAFAC components.

Synthesis and characterization of new derivatives of alginic acid and evaluation of their iron(III)-crosslinked beads as potential controlled release matrices.

CONTEXT: The excellent gelling and safety profiles of alginic acid combined, however, with drawbacks of its ionotropically crosslinked beads (i.e. their quick release of loaded drugs) prompted us to chemically modify alginic acid. OBJECTIVE: Alginic acid was chemically conjugated with four amines of varying hydrophilic-hydrophobic properties (i.e. tris(hydroxymethyl)methyl-, allyl-, benzyl- or pentyl-amines) in an attempt to enhance the drug release profiles from respective metal crosslinked beads. MATERIALS AND METHODS: Chemical conjugation procedures were performed using dicyclohexylcarbodiimide as a coupling agent and the resulting new derivatives were characterized using proton nuclear magnetic resonance ((1)H NMR), infrared (IR) spectroscopy and differential scanning calorimetry (DSC). These modified polymers were used to prepare iron (III)-crosslinked beads loaded with folic acid as model drug, which were tested in vitro to assess their folic acid release profiles. RESULTS AND DISCUSSION: Interestingly, the resulting beads accessed enteric release kinetics, with tris(hydroxymethyl)methyl-amide alginic conjugate producing most pronounced enteric profile. CONCLUSION: The results suggest the possibility of achieving controlled drug release from alginate-based beads via facile chemical modification of alginic acid.