Abstract
We investigated and monitored in situ the wetting and dissolution properties of polymeric nanofibers and determined the solid-state of a drug during dissolution. Piroxicam (PRX) was used as a low-dose and poorly-soluble model drug, and hydroxypropyl methylcellulose (HPMC) and polydextrose (PD) were used as carrier polymers for electrospinning (ES). The initial-stage dissolution of the nanofibers was monitored in situ with three-dimensional white light microscopic interferometry (SWLI) and high-resolution optical microscopy. The physical solid-state characterization of nanofibers was performed with Raman spectroscopy, X-ray powder diffraction (XRPD), and scanning electron microscopy (SEM). We showed that PRX recrystallizes in a microcrystalline form immediately after wetting of nanofibers, which could lead to enhanced dissolution of drug. Initiation of crystal formation was detected by SWLI, indicating: (1) that PRX was partially released from the nanofibers, and (2) that the solid-state form of PRX changed from amorphous to crystalline. The amount, shape, and size of the PRX crystals depended on the carrier polymer used in the nanofibers and dissolution media (pH). In conclusion, the present nanofibers loaded with PRX exhibit a quasi-dynamic dissolution via recrystallization. SWLI enables a rapid, non-contacting, and non-destructive method for in situ monitoring the early-stage dissolution of nanofibers and regional mapping of crystalline changes (re-crystallization) during wetting. Such analysis is crucial because the wetting and dissolution of nanofibers can greatly influence the performance of nanofibrous drug delivery systems in pharmaceutical and biomedical applications.
Highlights
In recent years, advanced polymeric nanofibrous drug delivery systems (DDSs) have been of increasing use in pharmaceutical and biomedical applications
We combined situ with three-dimensional white light microscopic interferometry (SWLI) and high-resolution optical microscopy to image PRX-loaded nanofibers in contact with an aqueous medium, and the physical appearance and solid-state changes of nanofibers were verified with scanning electron microscopy (SEM), Raman spectroscopy, and X-ray diffraction (XRD), respectively
This is the first time when such imaging and solid-state analyses are applied in a complimentary fashion to investigate the dissolution of polymeric nanofibers
Summary
In recent years, advanced polymeric nanofibrous drug delivery systems (DDSs) have been of increasing use in pharmaceutical and biomedical applications Such systems include oral dispersible thin films, ophthalmic preparations, multifunctional wound dressings, and implanted DDSs [1,2,3]. We combined SWLI and high-resolution optical microscopy to image PRX-loaded nanofibers in contact with an aqueous medium, and the physical appearance and solid-state changes of nanofibers were verified with scanning electron microscopy (SEM), Raman spectroscopy, and X-ray diffraction (XRD), respectively. To our knowledge, this is the first time when such imaging and solid-state analyses are applied in a complimentary fashion to investigate the dissolution of polymeric nanofibers
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