Microstructural Distinction of Electrospun Nanofibrous Drug Delivery Systems Formulated with Different Excipients

Abstract

The electrospun nanofiber-based orally dissolving webs are promising candidates for rapid drug release, which is due to the high surface area to volume ratio of the fibers and the high amorphization efficacy of the fiber formation process. Although the latter is responsible for the physical and/or chemical instability of these systems. The primary aim of the present study was to elucidate how the addition of polysorbate 80 (PS80) and hydroxypropyl-β-cyclodextrin (HP-β-CD) influenced the electrospinning process, the properties, and the behavior of the obtained nanofibers. In order to reveal any subtle changes attributable to the applied excipients, the prepared samples were subjected to several state of the art imaging and solid state characterization techniques at both macroscopic and microscopic levels. Atomic force microscopy (AFM) revealed the viscoelastic nature of the fibrous samples. At relatively low forces mostly elastic deformation was observed, while at higher loads plasticity predominated. The use of polysorbate led to about two times stiffer, less plastic fibers than the addition of cyclodextrin. The H-C nuclear magnetic resonance (NMR) cross-polarization build-up curves pointed out that cyclodextrin acts as an inner, while polysorbate acts as an outer plasticizer and, due to its "liquid-like" behavior, can migrate in the polymer-matrix, which results in the less plastic behavior of this formulation. Positron annihilation lifetime spectroscopy (PALS) measurements also confirmed the enhanced mobility of the polysorbate and the molecular packing enhancer properties of the cyclodextrin. Solid-state methods suggested amorphous precipitation of the active ingredient in the course of the electrospinning process; furthermore, the nature of the amorphous systems was verified by NMR spectroscopy, which revealed that the use of the examined additives enabled the development of a molecularly dispersed systems of different homogeneities. An accelerated stability study was carried out to track physical state related changes of the incorporated drug and the polymeric carrier. Recrystallization of the active ingredient could not be observed, which indicated a large stress tolerance capacity, but time-dependent microstructural changes were seen in the presence of polysorbate. Raman mapping verified homogeneous drug distribution in the nanofibrous orally dissolving webs. The performed dissolution study indicated that the drug dissolution from the fibers was rapid and complete, but the formed stronger interaction in the case of the PVA-CD-MH system resulted in a little bit slower drug release, compared to the PS80 containing formulation. The results obviously show that the complex physicochemical characterization of the polymer-based fibrous delivery systems is of great impact since it enables the better understanding of material properties including the supramolecular interactions of multicomponent systems and consequently the rational design of drug-loaded nanocarriers of required stability.

Influence of Aqueous Solubility-Enhancing Excipients on the Microstructural Characteristics of Furosemide-Loaded Electrospun Nanofibers

“…After 1, 2, 3 and 4 weeks of storage the samples were further examined by SEM, FTIR and XRD. The dissolution method was based on a previous study of our research group [18]; a small-volume dissolution method was used in order to mimic in-vivo buccal dissolution.…”

“…Solubilizers are often used in pharmaceutical formulations to improve the aqueous solubility of drugs with poor solubility. On the other hand, solubilizers can influence the mechanical properties of the system by acting as plasticizers, which can modify the characteristics of the drug delivery system advantageously or disadvantageously [18,19]. They can provide an improved dissolution rate for the drugs, enhance wettability and help to avoid the precipitation of the active compound, but they also can contribute to the better physical stability of the formulation by reducing the recrystallization of the drug [12,20].…”

“…A comprehensive microstructural study with an examination of the supramolecular interactions of the compounds of the formulations [18] provides essential information about the prediction of the functional properties of the system. Special concern is required in the case of furosemide for the crystalline or amorphous state of the drug, the identification of amorphous acid or the amorphous salt state, which have particular relevance for stability prediction for the systems during storage [25].…”

Electrospinning of Cyclodextrin Functional Nanofibers for Drug Delivery Applications

“…The results showed that the use of CyD molecules led to controlled release, and 17% decrease in the burst release was observed, followed by a quantifiable sustained release up to two days. Metoclopramide hydrochloride (MH), a drug molecule that has been used to treat nausea and vomiting, was incorporated into HP-β-CyD functional PVA nanofibers, and the release of MA was performed in a phosphate buffer (pH = 6.8) at 37 °C [126]. 90% Release of MA took place in 1 min due to burst release of MA.…”

Release Profile of Gentamicin Sulfate from Polylactide-co-Polycaprolactone Electrospun Nanofiber Matrices

“…Compared with other formulations, electrospinning affords great flexibility in selecting and combining materials and drugs. Drug molecule encapsulation into electrospun polymer nanofibers, promotes intimate drug to polymer contact, also modifying drug apparent solubility [3,4,5,6,7,8,9,10,11]. As far as electrospun materials are concerned, the ability of reaching high encapsulation efficiencies, simultaneous delivery of diverse drugs, and drug release modification are recognized as significant advantages.…”