The objectives of this study are the development and evaluation of modified release multi-particulate drug delivery systems containing a BCS class II drug (meloxicam), formulated as polymer-coated pellets. Inert seeds containing microcrystalline cellulose, lactose monohydrate, and polyvinylpyrrolidone were prepared by extrusion-spheronization. The obtained cores were loaded with meloxicam using the drug layering technique, by spray coating in a fluidized bed with a liquid dispersion of the drug. The resulting drug pellets were film-coated with various polymers (Acryl-EZE^® 93O, Eudragit^® RS 30-D as well as experimental composite obtained by adding Methocel™ E5 Premium LV as pore forming agent to the extended release polymer Eudragit^® RS 30-D). All experimental systems were evaluated by scanning electron microscopy and in vitro release testing, in an attempt to investigate the characteristics of the film coatings and their influence on drug release from the multi-particulate systems. The in vitro release study was performed in two stages, using two media with pH values corresponding to the gastric and intestinal environment (HCl 0.1N, pH = 1.2 for the first two hours of the test and phosphate buffer 50 mM, pH 6.8 for the next 4 h). The in vitro release data have highlighted the impact of the formulation factors on the drug release.

Clozapine and its metabolites require close therapeutic monitoring (TDM) in patients due to poor correlation between the administrated doses and resulting plasma concentrations, the narrow therapeutic interval, high inter-individual variability, and the risk of serious side effects once toxic levels are exceeded. The aim of the study was to develop a simple (relatively cheap) LC-UV method for the quantification of clozapine and its metabolites in plasma and urine samples. For sample preparation, liquid-liquid extraction (LLE) in n-octanol was more efficient and less limiting in injection volumes compared to the in-situ formation of SUPRAS. When analyzing urine, an alkalinization step before extraction was required. The proposed method produced linear concentration responses with/without internal standard (IS) for the target analytes, with LLOQs within the targeted range of 50 ppb and %RSD within the acceptable 15% range. Furthermore, sample stability studies proved that pre-extracted samples were stable for the short term at room temperature and long-term when frozen.