IN-VITRO DISSOLUTION STUDY OF MELOXICAM IMMEDIATE RELEASE PRODUCTS USING FLOW THROUGH CELL (USP APPARATUS 4) UNDER DIFFERENT OPERATIONAL CONDITIONS

Objective: To evaluate and compare the in-vitro dissolution profiles of five generic immediate release (IR) products of Meloxicam (MX) available in Egyptian market with the innovator reference product (Mobic®, R) using different operational conditions of the flow through dissolution cell (FTC, USP Apparatus 4), in phosphate buffer (pH=7.5). Methods: The comparative in-vitro dissolution studies were performed under different FTC operational conditions such as cell size, tablet position within the cell, open and closed loops setup and type of flow (laminar and turbulent) on MX dissolution rate from different IR products. Results: The study showed that two generic products, out of five, gave similar dissolution profiles with R using a specified well controlled condition of FTC. A selected generic product (Mobitil, G1) was tested versus R under different operational conditions of the FTC such as cell size, type of flow, tablet position and open & closed loops setup. The dissolution profile of MX from R was highly affected by changing the tablet position, slightly affected by the open & closed loops setup and not affected by cell size and type of flow. On the other hand, the dissolution profile of MX from G1 was affected by all the previous operational conditions. Comparing ƒ2 values between G1 against R among the different operational conditions proposed, only one in-vitro dissolution test showed similar dissolution profile of G1 with respect to R. Conclusion: Three generic products of MX might not be interchangeable with the innovator product (Mobic®)

IN VITRO EVALUATION OF IBUPROFEN HOT-MELT EXTRUDED PELLETS EMPLOYING DIFFERENT DESIGNS OF THE FLOW THROUGH CELL

Objective: Hot-melt extrusion technique (HME) was used to prepare a sustained release (SR) multiparticulate oral dosage form (pellets) containing Ibuprofen (IBU). Prepared IBU-HME pellets were in vitro evaluated by flow-through cell dissolution tester (FTC, USP Apparatus #4) using different flow conditions and FTC designs. Methods: In this study, Sucroester®WE15 was used as the polymeric carrier to prepare two different IBU loadings (60 % and 30 % w/w). In order to optimize the FTC conditions, different cell sizes, pellets loading and hydrodynamic conditions of FTC on IBU release rate from pellets were proposed. Results: The results showed that the IBU release rate was increased in the larger cell than the small cell. In addition, laminar flow showed more reproducible results than turbulent flow. It was found that the large cell with laminar flow rate and homogeneous mixing of the pellets with glass beads was the optimum conditions for in vitro evaluation of these preparations. Conclusion: Improper methods of sample loading as well as cell size may result in confusing or erroneous data if not analyzed carefully. Therefore, it might be critical to choose a specific cell design of the FTC for in vitro evaluation of pellets to obtain reliable and discriminative results reflecting the major as well as minor formulation variables

Stability and bioavailability of diltiazem/polyethylene oxide matrix tablets

<p>The aim of this study was to prepare and evaluate <i>in vitro</i> and <i>in vivo</i>; Diltiazem-Hydrochloride (DTZ) in sustained-release matrix tablets. Stability of DTZ tablets prepared with polyethylene oxide (MWs 900 000, 4 000 000, and 8 000 000) with or without addition of electrolytes was carried-out for 1-month, under short-term storage at 40 °C/75% RH. Stability was evaluated by DTZ content, DSC and drug release using the Flow-Through Cell (USP # IV). The majority of stored tablets were stable for 1-month under short-term storage with respect to DTZ content and drug release. DSC curves of stored samples showed appearance of new exothermic peak after 1-month storage at 40 °C/75% RH, which was not observed after 5 years storage at room temperature. A selected formula was tested <i>in vivo</i> against reference product on eight healthy human volunteers. DTZ-plasma profiles were different between the two formulae. However, no statistically significant differences were detected between <i>C</i>_max, AUC_0–48 and AUC_0–∞. The two products were therapeutically in-equivalent, as 90% confidence intervals “T/R” were 88.82–205.76, 91.40–139.94, and 93.73–134.97 for <i>C</i>_max, AUC_0–48 and AUC_0–∞, respectively. This study highlighted possible differences observed between the two regimes frequently applied for stability testing.</p