The role of excipient molecular weight in drug release by fibrous dosage forms with close packing and high drug loading

In this work, drug release by highly drug-loaded, densely-packed fibrous dosage forms is investigated. The formulations consisted of 87wt% ibuprofen drug and 13wt% hydroxypropyl methyl cellulose (HPMC) excipient of molecular weights 10, 26, or 86 kg/mol. The dosage forms were prepared by 3D-patterning a drug-excipient-water paste in a cross-ply arrangement, and drying. Scanning electron microscopy revealed that due to drying the fibers developed a porosity of about 15% by volume.

Upon immersion in a dissolution fluid, the dosage form with 10 kg/mol excipient fragmented and dissolved in 10 minutes. The dosage form with 26 kg/mol excipient fragmented, too, but dissolved in 60 minutes. With the 86 kg/mol excipient, however, no fragmentation was observed; instead a thick, high-viscosity mass was formed that eroded slowly, in 500 minutes. Theoretical models suggest that the dissolution fluid rapidly percolates the inter-fiber void space, and a capillary pressure develops in the pores of the fibers. The fluid then diffuses into the fibers, and they transition to a viscous suspension which fragments and dissolves rapidly, if the viscosity is low (as for the 10 kg/mol excipient).

The fragmentation and dissolution rates decrease if the molecular weight of the excipient is increased, and if it is very large, an unfragmented, high-viscosity mass is formed from which drug release is slow. Thus by tailoring the molecular weight of the excipient, a large range of drug release rates of highly drug-loaded and close-packed fibrous dosage forms can be realized. Continue on The role of excipient molecular weight in drug release by fibrous dosage forms with close packing and high drug loading

Keywords: Fibrous dosage forms, Highly drug loaded dosage forms, Drug release, Excipient molecular weight, Pharmaceutical tablets, 3D-micro-patterning, 3D-printing