429655 Pharmaceutical Production of Drug-Eluting Nanofibers By Precise Engineering of Needleless Electrospinning with an Oscillating Carriage

Tuesday, November 10, 2015: 5:09 PM
253B (Salt Palace Convention Center)
Ryan Stoddard and Kim A. Woodrow, Bioengineering, University of Washington, Seattle, WA

Electrospun nanofibers have been broadly investigated as medical fabrics in applications for drug delivery, tissue engineering, and wound healing[1]. These pharmaceutical applications of nanofibers will require a scalable process to produce precise fabric homogeneity and drug loading, which has yet to be demonstrated on a manufacturing scale instrument. Free surface or “needleless” electrospinning is a versatile and scalable method being evaluated for high throughput nanofiber production. A recent development in manufacturing scale needleless electrospinning equipment is the oscillating carriage method for solution entrainment onto a stationary wire electrode, which addresses scalability concerns with the current rotating wire entrainment method[2]. However, a narrow physical understanding of the oscillating carriage method has constrained its applications exclusively to low basis weight nanofiber coatings in the filtration industry[3].  In contrast to filtration coatings, electrospun medical fabrics are more challenging to manufacture due to requirements for fabricating high basis weight, stand alone materials that are needed to realize certain clinical applications.

Here, we present a process to use an oscillating carriage free surface electrospinning platform to fabricate uniform and high basis weight fiber mats loaded with tenofovir (TFV), an antiretroviral drug that inhibits HIV. TFV-loaded nanofibers were electrospun from a blend of polyvinyl alcohol and polyethylene oxide (PVA-PEO) polymers to produce 50-120 grams per square meter basis weight fabrics. We observed a mass accumulation of uniform material of approximately 3 grams per hour, which is a 12-fold increase from our typical process performance. This improvement was realized through isolated optimization of throughput, cross-direction uniformity, and machine-direction uniformity. Statistically designed screening experiments for the oscillating carriage entrainment method showed drug loading, polymer molecular weight, electrode distance, electric field intensity, and collecting electrode geometry are all significant in explaining process throughput and content uniformity. For the rotating wire geometry, significant variables only emerged to describe throughput whereas a strategy for optimizing content uniformity was not identified. Using these response outcomes and empirical observations of the electrospinning process, we developed a model describing the nanofiber mass deposition profile as a function of jet spacing, entrainment volume, jet initiation time, jetting time, polymer concentration, carriage speed, and wire length. This model allows us to derive a general optimization approach for any material composition. We expect our findings and analysis of the oscillating carriage entrainment method for needleless electrospinning will advance the pharmaceutical production of other novel medical fabrics.

[1] Meinel, A. J.; Germershaus, O.; Luhmann, T.; Merkle, H. P.; Meinel, L. European Journal of Pharmaceutics and Biopharmaceutics 2012, 81, 1.

[2] Forward, K. M.; Rutledge, G. C. Chemical Engineering Journal 2012, 183, 492.

[3] Petrik, S.; Maly, M. In Materials Research Society; Tanioka, A., Ed. Boston, MA, USA, 2009; Vol. 1240

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