Microstructural effects in drug release by solid and cellular polymeric dosage forms: A comparative study


In recent studies, we have introduced melt-processed polymeric cellular dosage forms to achieve both immediate drug release and predictable manufacture. Dosage forms ranging from minimally-porous solids to highly porous, open-cell and thin-walled structures were prepared, and the drug release characteristics investigated as the volume fraction of cells and the excipient molecular weight were varied. In the present study, the relative weight fractions of the drug and the excipient are changed over a large range and their effect on the drug release rate is investigated. Both minimally-porous solid structures and cellular dosage forms consisting of various weight fractions of Acetaminophen drug and polyethylene glycol (PEG) excipient are prepared and tested. Results of dissolution experiments show that the non-porous dosage forms disintegrate and release drug by slow surface erosion, and the erosion rate and specific drug release rate decrease as the drug weight fraction is increased. By contrast, the open-cell structures disintegrate rapidly by viscous exfoliation, and the disintegration rate is independent of drug weight fraction. Erosion models suggest that the non-porous solid dosage forms erode by convective mass transfer of the excipient if the drug volume fractions are small. At larger drug volume fractions, however, the slower-eroding drug particles hinder access of the free-flowing fluid to the excipient, thus slowing down erosion of the composite solid. The disintegration rate of the cellular dosage forms, by contrast, is limited by diffusion of the dissolution fluid into the excipient phase of the thin cell walls. Because the wall thickness is of the order of the drug particle size, the drug particles cannot hinder diffusion through the excipient across the walls, and thus the specific drug release rate is mostly unaffected by the weight fraction of drug.