Controlled-release solid dispersions of Eudragit® FS 100 and poorly soluble spironolactone prepared by electrospinning and melt extrusion (original) (raw)
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Journal of Pharmaceutical Sciences, 2013
The solvent-free melt electrospinning (MES) method was developed to prepare a drug delivery system with fast release of carvedilol (CAR), a drug with poor water solubility. To the authors knowledge, this is the first report for preparing drug-loaded melt electrospun fibers. Cationic methacrylate copolymer of Eudragit R E type was used as a fiber forming polymer matrix. For comparison, ethanol-based electrospinning and melt extrusion (EX) methods were used to produce samples that had the same composition as the melt electrospun system. According to the results of scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, and Fourier transformed infrared spectrometry investigations, amorphous solid nanodispersions/solutions of CAR in Eudragit R E matrix were obtained in all cases with 20 m / m % drug content. In vitro drug release in acidic media from the extrudates was significantly faster (5 min) than that from crystalline CAR. Moreover, ultrafast drug release was achieved from the solvent-free melt and ethanol-based electrospun samples because of their huge surface area and the soluble polymer matrix in the acidic media. These results demonstrate that solvent-free MES is a promising, novel technique for the production of drug delivery systems with enhanced dissolution because it can combine the advantages of EX (e.g., solventfree, continuous process, and effective amorphization) and solvent-based electrospinning (huge product surface area).
Electrospun Fibers of Enteric Polymer for Controlled Drug Delivery
The production of electrospun fibers of enteric polymer for controlled delivery of drugs represents a simple and low cost procedure with promising advantages relative to the longer therapeutic window provided by cylindrical geometry in association with intrinsic properties of pH-dependent drug carriers. In this work, we have explored the incorporation of additives (block copolymers of poly(ethylene)-b-poly(ethylene oxide)) into matrix of Eudragit L-100 and the effective action of hybrid composites on delivery of nifedipine, providing improvement in the overall process of controlled release of loaded drug
Journal of pharmaceutical sciences, 2014
Melt electrospinning (MES) was used to prepare fast dissolving fibrous drug delivery systems in the presence of plasticizers. This new method was found promising in the field of pharmaceutical formulation because it combines the advantages of melt extrusion and solvent-based electrospinning. Lowering of the process temperature was performed using plasticizers in order to avoid undesired thermal degradation. Carvedilol (CAR), a poorly water-soluble and thermal-sensitive model drug, was introduced into an amorphous methacrylate terpolymer matrix, Eudragit® E, suitable for fiber formation. Three plasticizers (triacetin, Tween® 80, and polyethylene glycol 1500) were tested, all of which lowered the process temperature effectively. Scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, and Raman microspectrometry investigations showed that crystalline CAR turned into an amorphous form during processing and preserved it for longer time. In vitro dissolution st...
Express Polymer Letters, 2018
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.
Molecular pharmaceutics, 2018
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 plasti...
Journal of Nanoscience and Nanotechnology, 2017
In this study, poly(D,L-lactic acid)-polyethylene glycol-poly(D,L-lactic acid), hereafter referred to as PDLLA-PEG-PDLLA, triblock copolymer membranes were prepared by electrospinning. Scanning electron microscopy images revealed the morphology of the microfibers, which had a diameter ranging from 300 to 900 nm. Fourier transform infrared spectroscopy was employed for structural analysis of the PDLLA-PEG-PDLLA/florfenicol (FF) membranes, which exhibited three absorption peaks at 3455, 1684, and 1533 cm −1 , respectively, indicating that the triblock copolymer and FF are very well blended in the composite membranes. Differential scanning calorimetry revealed that weak interaction possibly decreased the activity of the segment and elevated the T g from 43 C to 46 C. From the in vitro dissolution tests, PDLLA as a biodegradable and biocompatible polymer can improve the solubility of FF. The rate of drug release increased with increasing PEG proportion. Furthermore, tensile and nanoindentation tests demonstrated that nanofibers exhibit mechanical properties such as tensile stress (700-2800 KPa), strain (40-120%), and good toughness (0.28-0.98 GPa). In conclusion, PDLLA-PEG-PDLLA nanofibers as a carrier improve the solubility of FF and control drug release.
Electrospinning of drug-loaded polymer systems: Preparation and drug release
Journal of Applied Polymer Science, 2011
In this study, biomedical devices for tissue regeneration loaded with anti-inflammatory drugs were formulated and characterized. We realized these systems by homogenously dispersing an interclay, a lamellar hydrotalcite loaded with diclofenac sodium (HTlc-DIC), in a polymeric matrix made of poly(e-caprolactone) to produce a controlled release of the drug. These biomedical devices were obtained with the electrospinning technique, which has proven to be very efficient. In particular, in this study, microfibers loaded with HTlc-DIC were obtained, and the drug delivery of diclofenac sodium from these systems was studied and compared with the release from biomedical devices loaded with the free drug. We analyzed these results by evaluating the diffusivity coefficient by means of the pure diffusive mathematical model. V
European Journal of Pharmaceutical Sciences
The present study introduces a modified melt-electrospinning (MES) method for fabricating the melt-electrospun fibers (MSFs) of a poorly water-soluble drug and carrier polymer. The MES of poorly water-soluble model drug indomethacin (IND) and hydrophilic carrier polymer, Soluplus ® (SOL) were prepared at a 1:3 drug-polymer weight ratio. Water was used as an external plasticizer to regulate a MES processing temperature and to improve fiber formation. The fiber size, surface morphology, physical solid state, drug-polymer (carrier) interactions, thermal and chemical stability and dissolution behavior of MSFs were investigated. Solid state nuclear magnetic resonance spectroscopy (NMR) was used to measure T1(1 H), and the domain size of IND in MSFs (25-100 nm) was calculated from these results. Solid-state and thermal analysis confirmed the presence of amorphous solid dispersions of IND and SOL. IND was found to be chemically stable during an entire MES process. Only small drug content variability of different MSF batches was detected with high performace liquid chromatography (HPLC). Given findings were verified with the liquid NMR spectroscopy. The dissolution of MSFs was significantly faster than that of physical mixtures (PMs) or pure drug. The enhanced dissolution of MSFs was caused by high surface area, amorphous state of the drug and solubilizing properties of the carrier polymer (SOL).
Journal of Materials Chemistry, 2012
In drug therapy, most therapeutic drugs are of low molecular weight and could freely diffuse in the biological milieu depending on the administration route applied. The main reason for the development of polymeric drug carriers is to obtain desired effects such as sustained therapy, local and controlled release, prolonged activity and reduction of side effects. Alternatively, polymeric carriers can be made bioerodible in order to be eliminated by natural ways after a certain time of therapy. Core-shell fibres from coaxial spinneret or emulsion electrospinning are good candidates for the development of such devices; however difficulties remain especially in controlling the release over a sustained period. Here, we present a novel technique combining coaxial and emulsion electrospinning to produce microstructured core-shell fibres. The design of drug microreservoirs of variable size within the bulk of the fibre combined with a tailored diffusive barrier allows modulating the release kinetics of these novel carriers. A nearly constant and linear release of the model drug Levetiracetam (M w z 170 g mol À1 ) from PLGA emulsion-coaxial electrospun fibres is observed over 20 days. This device is aimed to be implanted into the brain for the treatment of epilepsy and is an example of the new capabilities and the promising potential that emulsion-coaxial electrospinning can provide towards the development of future drug carriers.
Pharmaceutics, 2021
In an attempt to improve the solubility of valsartan, a BCS II drug, fibers containing the drug were prepared from three water-soluble polymers, hydroxypropyl-methyl-cellulose (HPMC), polyvinyl-pyrrolidone (PVP), and polyvinyl-alcohol (PVA). Fiber spinning technology was optimized for each polymer separately. The polymers contained 20 wt% of the active component. The drug was homogenously distributed within the fibers in the amorphous form. The presence of the drug interfered with the spinning process only slightly, the diameters of the fibers were in the same range as without the drug for the HPMC and the PVA fibers, while it doubled in PVP. The incorporation of the drug into the fibers increased its solubility in all cases compared to that of the neat drug. The solubility of the drug itself depends very much on pH and this sensitivity remained the same in the HPMC and PVP fibers; the release of the drug is dominated by the dissolution behavior of valsartan itself. On the other han...