The application of polyethylene oxide (PolyOx(R)) and methoxypolyethylene glycol (Carbowax Sentry(R)) in the production of extruded-spheronized beads with a high drug load.

摘要

Part 1. The purpose of this study was to investigate the use of polyethylene oxide and methoxypolyethylene glycol in the manufacture of beads by extrusion-spheronization without inclusion of microcrystalline cellulose. Beads containing polyethylene oxide (PEO), methoxypolyethylene glycol (MPEG), and pseudoephedrine hydrochloride (PSE) were prepared. Release studies, bead yield, roundness, friability, and density were determined. Release profiles showed that there was immediate and complete release of drug from the beads. A five factor, half fraction screening design was employed to study the effect of formulation variables and process variables on the properties of the beads. Statistical analysis indicated that variables, such as the drug load, feeder, extruder, and spheronization rates, and spheronization time significantly affected the physical properties of the beads. Significant two-factor interactions between the variables also exist for all measured responses, demonstrating, in part, the value of statistical design.; Part 2. The purpose of this study was to investigate the mechanism(s) by which MPEG affected the properties of wetted PEO. Force of detachment (FOD) studies were performed with well hydrated mixtures of PSE, PEO, and MPEG. A three component, D-optimal mixture study was employed to clarify the effect of MPEG on the mixture. The FOD studies confirmed that wetted PEO significantly contributed to the increase in tackiness, MPEG was antagonistic to the influence of the wetted PEO, and no effect due to PSE could be supported. Temperature modulated differential scanning calorimetry (TMDSC) studies were performed on various combinations of both dry and wetted PEO with MPEG. TMDSC results demonstrated a mechanism that could explain the effect of MPEG on wetted PEO. Up to a certain PEO:MPEG mass ratio, MPEG can prevent water from occupying normal binding spots, ultimately weakening the formed hydrogel. Above the particular PEO:MPEG mass ratio, further addition of MPEG results in self-association, and no further effect is observed.