Combining restricted access material (RAM) and turbulent flow for the rapid on-line extraction of the cyclooxygenase-2 inhibitor rofecoxib in plasma samples.

Restricted access material (RAM) has been used in the packing of a solid-phase extraction (SPE) column for on-line extractions under turbulent flow conditions. The bio-compatible RAM material works by the principle of size exclusion in addition to conventional reversed-phase chromatography, thereby allowing the extraction and preconcentration of small analyte molecules from biological samples such as plasma. Using small column dimensions (0.76 mm x 50 mm) and a consequently high linear velocity, turbulent flow was achieved during online sample extractions. The improved mass-transfer rate characteristic of turbulent flow allows fast sample cleanup without decreased extraction efficiency. The novel use of the RAM column, connected upstream to a C18 monolithic column, allowed the direct injection, extraction, separation, and MS/MS detection of plasma samples spiked with rofecoxib in a span of 5 min. Calibration curves obtained using this RAM turbulent flow coupled column method showed good linearity (R2 > 0.99) and reproducibility (%RSD < or = 7%). The lower limit of quantitation of rofecoxib in plasma samples was found to be 40 ng/ml. The extraction method showed good recovery of rofecoxib from a plasma matrix with minimal signal loss and robustness after more than 200 plasma injections.

The effects of physical parameters on laser-induced breakdown spectroscopy analysis of intact tablets.

With the advent of the Food and Drug Administration initiatives to investigate and encourage the use of process analytical technologies, laser-induced breakdown spectroscopy (LIBS) is considered an excellent analytical tool to understand the processability of solid dosage form. In this article, the feasibility of the LIBS system for quantitation of active drug within a solid dosage form, as well as the effects of various physical parameters on its signal, is investigated. A model drug containing chlorine and sulfur was used. The examination of the specificity and reproducibility of the measurements led to the use of chlorine and carbon as the internal standard. An overall relative SD of 1.1% for the signal was found. For quantitation purposes, calibration curves using compound-X in formulated tablets were generated. It was found that curves generated from roller-compaction tablets generally gave higher LIBS signal than those generated using direct-compressed (DC) process. To investigate these differences, effect of LIBS signals from several physical properties of the tablets were examined. It was found that unmilled compound-X used in the manufacture of the tablets gave a LIBS signal 30% lower than when milled compound-X was used. However, by using multiple crushing-recompression DC process of the milled compound-X, the LIBS results were comparable with those found from both processed tablets using milled compound-X. Other physical parameters, such as wide ranges of granule size and tablet hardness found in the typical manufacturing process, had limited effect on the LIBS signal. From these results, it was noted that for accurate quantitation, it is necessary to use the same physical properties of compound-X and the same manufacturing process in the calibration standards as the actual samples.

Organogels and their use in drug delivery--a review.

Organogels are semi-solid systems, in which an organic liquid phase is immobilized by a three-dimensional network composed of self-assembled, intertwined gelator fibers. Despite their majoritarily liquid composition, these systems demonstrate the appearance and rheological behaviour of solids. Investigative research pertaining to these systems has only picked up speed in the last few decades. Consequently, many burning questions regarding organogel systems, such as the specific molecular requirements guaranteeing gelation, still await definite answers. Nonetheless, the application of different organogel systems to various areas of interest has been quick to follow their discoveries. Unfortunately, their use in drug delivery is still quite limited by the scarce toxicology information available on organogelators, as well as by the few pharmaceutically-accepted solvents used in gel systems. This review aims at providing a global view of organogels, with special emphasis on the interplay between the gelator's structural characteristics and the ensuing intermolecular interactions. A subsequent focus is placed on the application of organogels as drug delivery platforms for active agent administration via diverse routes such as transdermal, oral, and parenteral.

In situ-forming oleogel implant for rivastigmine delivery.

PURPOSE: To provide a simplified dosing schedule and potentially reduce side effects associated to peak plasma concentrations, an in situ-forming oleogel implant was studied for the sustained-release of rivastigmine. MATERIALS AND METHODS: The gel was prepared by dissolving 5-10% (w/w) N-stearoyl L: -alanine methyl ester (SAM) organogelator in safflower oil containing either dissolved rivastigmine or its dispersed hydrogen tartrate salt. Rheological analysis, differential scanning calorimetry, and infrared spectroscopy were carried out to assess the impact of drug incorporation on the oleogel; this was followed by in vitro and in vivo release studies. RESULTS: A weakening of intermolecular interactions was suggested by gel-sol transition temperature drops of 10-15 degrees C upon incorporation of dissolved drug. Meanwhile, the dispersed drug salt induced minimal or no changes in transition temperature. Gels containing dispersed rivastigmine had the lowest burst in vitro (<15% in 24 h). In vivo, the 10% SAM formulation containing dispersed rivastigmine provided prolonged drug release within the therapeutic range for 11 days, with peak plasma levels well below the toxic threshold and up to five times lower than for the control formulation. CONCLUSIONS: This study established SAM gels to be a promising option for sustained-release formulations in the treatment of Alzheimer's Disease.