Formulation Optimization of Polyox Based Modified Release Drug Delivery System

摘要

Polyethylene Oxide (PEOs) offer specific advantages to be used in pharmaceutical products as release modifiers by forming a hydrogel around the dosage form in aqueous environment causing the drug to follow a diffusional path before releasing into the media. The strength of the hydrogel governs the release retardation capacity of the PEO system. The objective of this dissertation work was to use the Design of Experiments methodology to develop and optimize a PEO based modified release formulation of a highly water-soluble drug like Metoprolol succinate. The effect of the different viscosity grade PEOs, their concentration with respect to the drug, combination of two different viscosity grades, % drug content in the formulation and the use of water soluble / insoluble fillers on the dissolution of metoprolol succinate was studied. The critical formulation parameters namely PEO concentration and % drug content were chosen as input factors and dissolution at 1, 4, 8 and 20 hours was recorded as responses to carry out optimization using the DOE approach. The results obtained after statistical treatment of data provided a design space that can be used for achieving the desired formulation profile. The model has been validated to predict the effect of the input factors (PEO type and concentration and % drug content) on the responses (in vitro dissolution).