Scalable electrospinning methods to produce high basis weight and uniform drug eluting fibrous biomaterials
Electrospinning is a material fabrication method which has been extensively researched for pharmaceutical dosage forms, filters, and tissue engineered scaffolds. Despite this interest, electrospinning methods have failed to create high basis weight materials with consistent fiber density. Therefore, electrospun materials are typically described to have limited three-dimensional structure, may require a large surface area to deliver a sufficient mass of drug, or may have nonuniform drug dosing with practical manufacturing methods which process multiple dosage forms by material area. Here, we show that free-surface electrospinning can generate materials with high throughput, high basis weight, and controllable deposition as relevant to scalable solid-dosage form production. Optimized free-surface electrospinning parameters, and the interaction of parameters, which significantly increase fiber throughput and disperse deposition were identified using design of experiments. Using the identified optimal settings for an aqueous polymer solution – including a lower polymer concentration, higher carriage speed, larger orifice size, and higher electric field – fibrous materials could be productively generated at 12.9 g/hr. Fibers were observed to collect with a gaussian distribution, and the standard deviation factor of this distribution was measured to change dependent on the specific polymer formulation. Simple simulations of material collection utilized this mass distribution value to predict material collection with oscillating, dynamic movement of the spinning substrate for both aqueous and organic polymer formulations. Dynamic spinning methods allowed for a larger collection area, greater surface density, and uniformity. Using simulated and experimental data, a defined region of consistent, 100 g/m2 basis weight fiber deposition could be achieved dependent on the dynamic path length and specific polymer formulation. These data represent a magnitude increase in achievable material basis weight, as compared to previously reported limitations for electrospinning. Finally, these free-surface electrospinning methods were used to formulate materials with three physicochemically diverse model pharmaceutical agents: maraviroc, raltegravir, and etravirine. Fiber deposition was shown to be consistent, as location defined samples in a representative sheet had less than a 10% coefficient of variation in mass or dosing of each drug. Across samples taken from various locations and sheet replicates, etravirine demonstrated efficient and consistent drug loading congruent with rigorous United States Pharmacopeia (USP) standards for dose uniformity. These data provide new proof-of-concept potential for electrospinning to manufacture medical biomaterials.
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