Electrospun papaverine hydrochloride-loaded nanofibrous sheets consist of hydroxypropyl cellulose/poly(vinyl alcohol) composite were prepared for buccal administration for cerebral ischemia. The nanofibrous drug delivery system was subjected to accelerated stability test for four weeks in order to scrutinize the solid state changes relating to the stress induced (40 2 degrees C/75 +/- 5% relative humidity) physical ageing. Micro- and macrostructural alterations were detected using scanning electron microscopy (SEM), Raman spectroscopy, Fourier transform infrared spectroscopy (FTIR) and positron annihilation lifetime spectroscopy (PALS). Significant changes were revealed at both supramolecular and macroscopic levels. Microscopic morphology uncovered major morphological transitions. Subtle variations of Raman and FTIR spectra indicated that the local chemical environment of papaverine was altered suggesting a partial phase transition of the active. Discrete o-Ps lifetimes and lifetime-distributions unveiled a two-step ageing process of the drug carrier. In addition to the tracking of the glassy-to-rubbery transition of the fiber forming polymers, the Raman spectroscopy enabled monitoring the kinetics of the phase transition observed. (C) 2017 Elsevier B.V. All rights reserved.