Amoxicillin chewable tablets intended for pediatric use: formulation development, stability evaluation and taste assessment.

To cover the unpleasant taste of amoxicillin (250 mg), maize starch (baby food) and milk chocolate were co-formulated. The raw materials and the final formulations were characterized by means of Dynamic Light Scattering (DLS), Differential Scanning Calorimetry (DSC) and Fourier-Transform Infrared (FT-IR) spectroscopy. To evaluate the taste masking two different groups of volunteers were used, according to the Ethical Research Committee of the Aristotle University of Thessaloniki. The optimization of excipients' content in the tablet was determined by experimental design methodology (crossed D-optimal). Due to the matrix complexity, amoxicillin was extracted using liquid extraction and analyzed isocratically by HPLC. The developed chromatographic method was validated (%Recovery 98.7-101.3, %RSD = 1.3, LOD and LOQ 0.15 and 0.45 µg mL-1 respectively) according to the International Conference on Harmonization (ICH) guidelines. The physicochemical properties of the tablets were also examined demonstrating satisfactory quality characteristics (diameter: 15 mm, thickness: 6 mm, hardness <98 Newton, loss of mass <1.0%, disintegration time ∼25min). Additionally, dissolution (%Recovery >90) and in vitro digestion tests (%Recovery >95) were carried out. Stability experiments indicated that amoxicillin is stable in the prepared formulations for at least one year (%Recovery <91).

Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) Containing Rice Bran Oil for Enhanced Fenofibrate Oral Delivery: In Vitro Digestion, Ex Vivo Permeability, and In Vivo Bioavailability Studies.

Lipid-based drug delivery systems (LbDDS), such as self-nanoemulsifying drug delivery systems (SNEDDS), constitute a prominent formulation approach for enhancing the aqueous solubility and oral bioavailability of poorly water-soluble compounds. Utilization of biorefinery wastes, such as oil from rice bran, may prove advantageous to both improving drug solubilization and absorption and to achieving sustainable agri-food waste valorization. Here, we assessed the effect of four SNEDDS compositions differing in the oil (rice bran oil and corn oil) and surfactant type (Kolliphor RH40 and EL) on the oral bioavailability of fenofibrate, a BCS class II compound. Prior to the in vivo oral administration of the SNEDDS in rats, drug solubilization was tested in vitro using the static digestion model, followed by the ex vivo permeability study of the predigested SNEDDS using the non-everted gut sac model. No significant variation was observed in the solubilization capacity within the different SNEDDS formulations. On the other hand, the ex vivo permeability data of the predigested SNEDDS correlated well with the in vivo bioavailability data designating the superiority of rice bran oil with Kolliphor EL as the surfactant, to enhance the oral absorption of fenofibrate. Results indicated that valorization of agro-industrial waste such as rice bran oil may prove useful in enhancing the oral performance of LbDDS in the case of fenofibrate, while at the same time maximizing the use of agricultural by-products via the creation of new sustainable value chains in the pharmaceutical field.

Solid-Phase Microextraction.

Undoubtedly, sample preparation is one of the most important steps in the analytical process [...].

Automated fluorimetric sensor for glutathione based on zone fluidics.

A zone-fluidics (ZF) based automated fluorimetric sensor for the determination of glutathione (GSH) is reported. Discrete zones of GSH and o-phthalaldehyde (OPA) mix and react on-line under mild basic pH without the need of additional nucleophillic reagents, to yield a fluorescent isoindole derivative (λex/λem = 340/425 nm). The proposed ZF sensor was optimized (pH, c(OPA), time, instrumental variables) and validated. Cysteine, glutamate, glycine and ammonium were representatively examined in terms of selectivity and were found not to react in 10-fold excess. Linearity was proved in the range of 5-100 µmol L-1 GSH, with an LOD of 1 µmol L-1 at a practical sampling rate of 20 h-1 and RSD < 0.5% (within-day) and 4.2% (day-to-day). The dosage uniformity of commercially available GSH - containing nutraceuticals was evaluated.

Development and validation of a rapid ultra high pressure liquid chromatographic method for the determination of methylxanthines in herbal infusions.

An ultra high pressure liquid chromatographic method coupled with diode array detector (UHPLC-DAD) has been developed and validated for the fast separation and determination of three major methylxanthines, i.e., caffeine, theophylline and theobromine, in various herbal beverages. Isocratic elution using 0.1vol% formic acid/CH3OH (92.5:7.5, v/v) enabled the completion of the separation cycle in less than 3min using a flow rate of 0.7mL/min and a column temperature of 50°C. Validation of the method included linearity (0.5-50mg/L), limits of detection (12-35µg/L) and quantification (40-120µg/L), precision, matrix effect and accuracy. The percent recoveries ranged between 90 and 108%.

Rapid determination of methylxanthines in real samples by high-performance liquid chromatography using the new FastGradient narrow-bore monolithic column.

The present study reports one of the very first analytical applications of the new narrow-bore monolithic column, FastGradient Chromolith (50mm x 2.0mm i.d.). The three major methylxanthines (theobromine, theophylline and caffeine) were separated rapidly and determined simultaneously in various real samples. Based on the unique characteristics of this novel monolithic column the analytes were separated efficiently (R(s)>3.0) in less than 5min at a low flow rate of 0.5mLmin(-1) and using a low volume fraction of organic solvent (5% acetonitrile (ACN) in water) in the mobile phase. UV detection was carried out at 274nm. The separation was optimized in terms of mobile phase composition, flow rate and injection volume, while the method was validated for linearity, detection and quantitation limits, within and day-to-day precision, accuracy and ruggedness. Its applicability was demonstrated by analyzing a variety of real samples including beverages, soft drinks, herbal products and pharmaceuticals. Compared to a well-established monolithic (Performance Chromolith 100mm x 4.6mm i.d.) and a particulate reversed phase column (Hypersil ODS 5microm 150mm x 4.6mm i.d.), the narrow-bore FastGradient column offered satisfactory performance, faster analysis time and drastic reduction in the consumption of mobile phase and organic solvents.

High throughput automated determination of glutathione based on the formation of a UV-absorbing thioacrylate derivative.

Sequential injection analysis (SIA) has been employed as the platform for the development of a high throughput automated assay for glutathione (GSH) in nutrition supplements. The proposed assay is based on the on-line formation of a UV-absorbing thioacrylate derivative (lambda(max) = 285 nm) upon reaction of thiol with the new reagent ethyl-propiolate (EP). This is the very first application of this reagent for the determination of GSH either in batch or continuous flow modes and the first SI method for the determination of GSH in pharmaceutical supplements. The various variables that typically affect such a protocol were studied, while thorough validation experiments according to established standards proved the reliability of the assay for the intended applications. As many as 100 sample injections were enabled per hour.