Manufacturing scale-up of electrospun poly(vinyl alcohol) fibers containing tenofovir for vaginal drug delivery

摘要

Electrospun fibers containing antiretroviral drugs have recently been investigated as a new dosage form for topical microbicides against HIV-1. However, little work has been done to evaluate the scalability of the fiber platform for pharmaceutical production of medical fabrics. Scalability and cost-effectiveness are essential criteria in developing fibers as a practical platform for use as a microbicide and for translation to clinical use. To address this critical gap in the development of fiber-based vaginal dosage forms, we assessed the scale-up potential of drug-eluting fibers delivering tenofovir (TFV), a nucleotide reverse transcriptase inhibitor and lead compound for topical HIV-1 chemoprophylaxis. Here we describe the process of free-surface electrospinning to scale up production of TFV fibers, and evaluate key attributes of the finished products such as fiber morphology, drug crystallinity, and drug loading and release kinetics. Poly(vinyl alcohol) (PVA) containing up to 60 wt% TFV was successfully electrospun into fibers using a nozzle-free production-scale electrospinning instrument. Actual TFV loading in fibers increased with increasing weight percent TFV in solution, and encapsulation efficiency was improved by maintaining TFV solubility and preventing drug sedimentation during batch processing. These results define important solution and processing parameters for scale-up production of TFV drug-eluting fibers by wire electrospinning, which may have significant implications for pharmaceutical manufacturing of fiber-based medical fabrics for clinical use.