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Abstract. Polymer-based electrospun amorphous solid dispersions (ASDs) were prepared and investigated from pharmaceutical application point of view. Spironolactone (SPIR) was used as model drug mixed in various concentrations with polymers suitable for fibre formation, such as vinylpyrrolidone-vinyl acetate copolymer, polyvinylpyrrolidone K30 and hydroxypropyl methylcellulose. Single needle electrospinning was applied at first for screening the composition of the prepared ASDs. Scaling-up the selected polymer-drug combination was accomplished by high speed electrospinning, the productivity of which enabled investigation of downstream processing to generate tablet formulation. The steps of a potential continuous production line (fibre collection, grinding, feeding and tableting) proved to be feasible with the electrospun ASD without any sign of crystallization. If crystalline drug was added into the ASD containing tablets as impurity strictly monotonous decrease of drug dissolution was observed in the function of the crystalline drug content. The capabilities of the non-destructive Raman and near-infrared spectroscopies, as fast quality assurance tools, were compared to each other in quantifying of crystalline SPIR content in the prepared tablets.
Keywords: industrial applications, high speed electrospinning, amorphous solid dispersions, tableting, continuous processing technologies
Received 3 November 2017; accepted in revised form 19 December 2017
(ProQuest: ... denotes formulae omitted.)
1. Introduction
Nowadays, significant part of active pharmaceutical ingredients (APIs) belongs to Class II of the Biopharmaceutical Classification System [1], that means these drugs possess low solubility and high permeability. By increasing the dissolution rate and extent of these drugs their inadequate bioavailability can be enhanced [2]. Polymers of high water solubility can form amorphous solid dispersions (ASDs) with such drugs improving their dissolution characteristics because there is no need of energy to break the crystal lattice structure [3]. Further advantages, such as reduced particle size, improved wettability and higher porosity, are also characteristic to ASDs [4]. That is why, this kind of formulation is getting to play a more and more important role in the pharmaceutical developments [5]. Among several melting, solvent and solvent-melting methods published for preparing ASDs [6], electrospinning (ES) capable of producing fibrous structures of large surface area seems to be especially favourable in the field of pharmaceutical application [7-18].
Although the electrospinning (ES) is fast developing with appearance of tri-axial, coaxial, side-by-side and their combination processes [19-22] the most common and facile ES...