title: Novel Alternating Current Electrospinning of Hydroxypropylmethylcellulose Acetate Succinate (HPMCAS) Nanofibers for Dissolution Enhancement: The Importance of Solution Conductivity.
abstract: Novel, high-yield alternating current electrospinning (ACES) and direct current electrospinning methods were investigated to prepare high-quality hydroxypropylmethylcellulose acetate succinate (HPMCAS) fibers for the dissolution enhancement of poorly soluble spironolactone. Although HPMCAS is of great pharmaceutical importance as a carrier of marketed solid dispersion-based products, it was found to be unprocessable using electrospinning. Addition of small amounts of polyethylene oxide as aid polymer provided smooth fibers with direct current electrospinning but strongly beaded products with ACES. Solution characteristics were thus modified by introducing further excipients. In the presence of sodium dodecyl sulfate, high-quality, HPMCAS-based fibers were obtained even at higher throughput rates of ACES owing to the change in conductivity (rather than surface tension). Replacement of sodium dodecyl sulfate with non-surface-active salts (calcium chloride and ammonium acetate) maintained the fine quality of nanofibers, confirming the importance of conductivity in ACES process. The HPMCAS-based fibers contained spironolactone in an amorphous form according to differential scanning calorimetry and X-ray powder diffraction. In vitro dissolution tests revealed fast drug release rates depending on the salt used to adjust conductivity. The presented results signify that ACES can be a prospective process for high-scale production of fibrous solid dispersions in which conductivity of solution has a fundamental role.
authors.affiliation: Organic Chemistry and Technology Department, Budapest University of Technology and Economics, Budapest 1111, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Balogh
authors.affiliation: Organic Chemistry and Technology Department, Budapest University of Technology and Economics, Budapest 1111, Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Farkas
authors.affiliation: Organic Chemistry and Technology Department, Budapest University of Technology and Economics, Budapest 1111, Hungary.
authors.forename: Ádám
authors.initials: Á
authors.lastname: Pálvölgyi
authors.affiliation: Organic Chemistry and Technology Department, Budapest University of Technology and Economics, Budapest 1111, Hungary.
authors.forename: András
authors.initials: A
authors.lastname: Domokos
authors.affiliation: Organic Chemistry and Technology Department, Budapest University of Technology and Economics, Budapest 1111, Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Démuth
authors.affiliation: Organic Chemistry and Technology Department, Budapest University of Technology and Economics, Budapest 1111, Hungary.
authors.forename: György
authors.initials: G
authors.lastname: Marosi
authors.affiliation: Organic Chemistry and Technology Department, Budapest University of Technology and Economics, Budapest 1111, Hungary. Electronic address: zsknagy@oct.bme.hu.
authors.forename: Zsombor Kristóf
authors.initials: ZK
authors.lastname: Nagy
mesh_terms: D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D005079:Excipients / Q000737:chemistry*; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D057139:Nanofibers / Q000737:chemistry* / Q000648:ultrastructure; D011092:Polyethylene Glycols / Q000737:chemistry; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D012995:Solubility; D013148:Spironolactone / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D005079:Excipients; D013148:Spironolactone; D012967:Sodium Dodecyl Sulfate; D011092:Polyethylene Glycols; C048331:hydroxypropylmethylcellulose acetate succinate; D008747:Methylcellulose
keywords: dissolution; excipients; formulation; nanotechnology; oral drug delivery; polymeric drug delivery systems; poorly water-soluble drugs; solid dispersion