This study was proposed to evaluate the effect of different cell designs and hydrodynamic conditions of the flow-through cell (FTC), USP dissolution Apparatus 4, on the release rate of a sustained-release product. Sustained-release (SR) diclofenac sodium (DS), 100 mg/tablet, was selected for this study. Different cell sizes and types, the flow rate of dissolution medium, and the tablet position within the FTC were considered. Results revealed that some of these variables affect the release rate of DS. It was obvious that the turbulent flow of the dissolution medium resulted in a higher DS release rate compared with the laminar flow. In addition, the results show that the drug release rate decreased when the tablet was buried in the glass beads compared with the unburied tablet. On the other hand, variables such as cell size (12-mm and 22.6-mm diameter), flow rates (8 and 16 mL/min), and presence of a tablet holder had a negligible role in drug release rate.

No abstract

No abstract

An HPLC/UV method to monitor meloxicam (MX) in human plasma was developed and properly validated. This method was based on a reversed-phase chromatographic analysis using C18-Symmetry column and a mobile phase consisting of acetonitrile: deionized water [50:50 (% v/v)] adjusted to pH 3 with glacial acetic acid. The detection wavelength was 360 nm using piroxicam as an I.S. The developed HPLC method was linear, sensitive, accurate, precise, selective and stable. This method exclusively provided a LLOQ of 5 ng/mL and ULOQ of 3000 ng/ml which could be considered as an excellent and economical method for carrying-out BA/BE studies. The determination of pharmacokinetics of single oral dose (15 mg/tablet) administered to healthy human male volunteer was carried-out to compare the bioavailability of three different MX products with a washout period of 8-days between treatments. Moreover, a comparative in vitro dissolution study of the three products using USP#4 (the Flow-through cell, FTC) has been carried-out prior to the in vivo test. The pharmacokinetic data revealed that the developed HPLC method was sensitive enough to monitor the multiplepeak phenomena characterized for MX absorption. Where, the first Cmax appeared at 4.5-5.5 hrs and the second at 10-12 hrs, for the tested products.

The objective of this study was to develop controlled porosity osmotic pump (CPOP) tablets of diclofenac sodium (DS). The influence of different cores (polymers and osmogens) and coats (thickness and porosigen content) on DS release were studied. Results revealed that decreasing HPMC viscosity grade from 4000cp (K4M) to 15cp (E15) increased DS release. While increasing the tablet coat thickness decreased DS release. The presence of osmogen increased DS release in the following rank: mannitol > lactose > avicel. There was a direct relationship between increasing PEG-400 in the coating solution and the amount of drug released in all formulations studied, except in one condition. A comparative bioavailability study using a selected CPOP formulation (T) versus the innovator product (R) revealed that CPOP tablet maintained a less fluctuated DS plasma concentration for up to 24 h with a detected mean Cmax of 836.8 ± 142.4 and 445.0 ± 81.0 ng/mL for R and T, respectively. There were no statistically significant differences between R and T, concerning AUC0-24 and AUC0-∞. Moreover, the appearance of the multi-peak phenomenon, which is frequently observed with DS absorption, was found in only 25% of volunteers in case of T versus 75% in case of R.