Deng-Guang Yu

Oral fast-dissolving drug delivery membranes prepared from electrospun polyvinylpyrrolidone ultrafine fibers

Oral fast-dissolving drug delivery membranes (FDMs) for poorly water-soluble drugs were prepared via electrospinning technology with ibuprofen as the model drug and polyvinylpyrrolidone (PVP) K30 as the filament-forming polymer and drug carrier. Results from differential scanning calorimetry, x-ray diffraction, and morphological observations demonstrated that ibuprofen was distributed in the ultrafine fibers in the form of nanosolid dispersions and the physical status of drug was an amorphous or molecular form, different from that of the pure drug and a physical mixture of PVP and ibuprofen. Fourier-transform infrared spectroscopy results illustrated that the main interactions between PVP and ibuprofen were mediated through hydrogen bonding. Pharmacotechnical tests showed that FDMs with different drug contents had almost the same wetting and disintegrating times, about 15 and 8 s, respectively, but significantly different drug dissolution rates due to the different physical status of the drug and the different drug-release-controlled mechanisms. 84.9% and 58.7% of ibuprofen was released in the first 20 s for FDMs with a drug-to-PVP ratio of 1:4 and 1:2, respectively. Electrospun ultrafine fibers have the potential to be used as solid dispersions to improve the dissolution profiles of poorly water-soluble drugs or as oral fast disintegrating drug delivery systems.

Electrospun diclofenac sodium loaded Eudragit® L 100-55 nanofibers for colon-targeted drug delivery

Eudragit® L 100-55 nanofibers loaded with diclofenac sodium (DS) were successfully prepared using an electrospinning process, and characterized for structural and pharmacodynamic properties. The influence of solvent and drug content on fiber formation and quality was also investigated. Fiber formation was successful using a solvent mixture 5:1 (v/v) ethanol:DMAc. XRD and DSC analysis of fibers confirm electron microscopic evidence that DS is evenly distributed in the nanofibers in an amorphous state. FTIR analysis indicates hydrogen bonding occurs between the drug and the polymer, which accounts for the molecular integration of the two components. In vitro dissolution tests verified that all the drug-loaded Eudragit® L 100-55 nanofibers had pH-dependent drug release profiles, with limited, less than 3%, release at pH 1.0, but a sustained and complete release at pH 6.8. This profile of properties indicates drug-loaded Eudragit® L 100-55 nanofibers have the potential to be developed as oral colon-targeted drug delivery systems.

Third generation solid dispersions of ferulic acid in electrospun composite nanofibers

Third generation solid dispersions (SDs) of ferulic acid (FA) in composite nanofibers were prepared using electrospinning. The spinning liquids involved co-dissolving solutions of FA, polyvinylpyrrolidone (PVP), sodium dodecyl sulfate (SDS) and sucralose in 75% ethanol aqueous solutions. FESEM observations showed that the nanofibers were assembled in a homogeneous web structure that had a smooth cross-section and surface with an average diameter of 254±32 nm. Results from DSC and XRD suggested that FA, SDS and sucralose were distributed in the PVP fibers in an amorphous manner and this is due to their compatibility resulting through a second-order interactions, as demonstrated by ATR-FTIR spectra. In vitro dissolution and permeation tests showed that the nanofiber-based SDs could release all the contained FA within 1 min and had a 13-fold higher permeation rate across sublingual mucosa compared to crude FA particles. The casting films have the same compositions as the nanofibers and belong to the third generation SDs, they gave the same solubility of FA as the nanofibers, and also exhibited a much faster dissolution rate than pure FA particles. It felt that electrospinning can be taken to prepare new generation SDs with structural characteristics that enhancing absorbance of poorly soluble drugs.

Multicomponent Amorphous Nanofibers Electrospun from Hot Aqueous Solutions of a Poorly Soluble Drug

ABSTRACTPurposeTo design and fabricate multicomponent amorphous electrospun nanofibers for synergistically improving the dissolution rate and permeation profiles of poorly water-soluble drugs.MethodsNanofibers were designed to be composed of a poorly water soluble drug, helicid, a hydrophilic polymer polyvinylpyrrolidone as filament-forming matrix, sodium dodecyl sulfate as transmembrane enhancer and mannitol as taste masking agent, and were prepared from hot aqueous co-dissolving solutions of them. An elevated temperature electrospinning process was developed to fabricate the composite nanofibers, which were characterized using FESEM, DSC, XRD, ATR-FTIR, in vitro dissolution and permeation tests.ResultsThe composite nanofibers were homogeneous with smooth surfaces and uniform structure, and the components were combined together in an amorphous state because of the favorable interactions such as hydrogen bonding, electrostatic interaction and hydrophobic interactions among them. In vitro dissolution and permeation tests demonstrated that the composite nanofibers had a dissolution rate over 26-fold faster than that of crude helicid particles and a 10-fold higher permeation rate across sublingual mucosa.ConclusionsA new type of amorphous material in the form of nanofibers was prepared from hot aqueous solutions of multiple ingredients using an electrospinning process. The amorphous nanofibers were able to improve the dissolution rate and permeation rate of helicid.

Microencapsulation of tamoxifen: Application to cotton fabric

Tamoxifen microcapsules and drug loaded medicated fabrics were investigated. The microcapsules were prepared using a complex coacervation procedure involving gelatin B and acacia gum. The morphology, particle size, drug loading capacity and in vitro release characteristics of the drug microcapsules were optimized for coating tamoxifen microcapsules onto the cotton fabrics. Infrared (IR) spectra and SEM were used to characterize the medicated fabrics and air permeability and laundering testing were undertaken to determine the efficiency and effectiveness of the system. Results showed that optimum condition for the microcapsules was at drug/polymer ratio 1:4, polymer concentration 3%, and rate of stirring 1000 rpm. In vitro release assays demonstrated that the tamoxifen was liberated over 10h after an initial bust rate period. SEM images illustrated that the tamoxifen microcapsules were spherical in shape and were also tightly fixed on to the cotton fabrics fast. These observations demonstrate that we have designed and fabricated a medicated system that potentially could be applied within a transdermal drug delivery system and so act in a system for the treatment of breast cancer.

Novel drug delivery devices for providing linear release profiles fabricated by 3DP.

Novel doughnut-shaped multi-layered drug delivery devices (DDDs) were developed with local variations of the drug and release-retardant material for providing linear release profiles. Based on computer-aided design models, different DDDs containing acetaminophen as a model drug, hydroxypropyl methylcellulose as matrix and ethyl cellulose (EC) as a release-retardant material were prepared automatically using a three-dimensional printing (3DP) system. In vitro dissolution assays demonstrated that all the 3DP DDDs had with different diameters, heights, concentrations of EC and central hole diameters were able to give linear release profiles. Morphological and erosion studies showed that acetaminophen was released through a simultaneous surface erosion process involving the outer peripheries and inner apertures. The barrier layers on both bases of DDDs had good adhesion strength with the drug-contained regions and offered consistent release retardation for the whole duration of the dissolution process. The release time periods of the DDDs were dependent on the annular thicknesses or the passes of binder solution containing a release-retardant material. The dosage of the DDD can be adjusted independently by changing the heights of the DDDs. Thus, 3DP is capable of offering novel strategies for developing DDDs with complex design features for desired drug release profiles.

Improving polymer nanofiber quality using a modified co-axial electrospinning process

Based on a modified coaxial electrospinning process and suitable selection of solvent mixtures as sheath fluid, a new strategy is presented for systematically improving polymer nanofiber quality. A concentric spinneret with an indented inner capillary is designed for the modified coaxial electrospinning. With a solution of 12% w/v PVP K60 in ethanol as the core electrospinning fluid, six solvents are used as sheath fluids to investigate the impact of solvent properties on the resultant PVP nanofiber quality. The PVP nanofiber quality is closely related to solvent physical-chemical properties. High quality PVP nanofibers of average diameter 130u2009±10u2009nm with homogeneous structures and smooth surfaces are created using a solvent mixture of acetone, ethanol and DMAc in the ratio of 3:1:1(v/v/v).

Dissolution improvement of electrospun nanofiber-based solid dispersions for acetaminophen.

The objective of the present investigation was to prepare novel solid dispersions (SDs) of poorly water-soluble drugs with special microstructural characteristics using electrospinning process. With the hydrophilic polymer polyvinylpyrrolidone as the filament-forming polymer and acetaminophen (APAP) as the poorly water-soluble drug model, SDs having a continuous web structure, and in the form of non-woven nanofiber membranes, were successfully prepared. The electrospun nanofiber-based SDs were compared with those prepared from three traditional SD processes such as freeze-drying, vacuum drying, and heating drying. The surface morphologies, the drug physical status, and the drug-polymer interactions were investigated by scanning electron microscopy, differential scanning calorimetry, X-ray diffraction, and attenuated total reflectance Fourier transform infrared. In vitro dissolution tests demonstrated that the electrospun nanofibers released 93.8% of the APAP content in the first 2 minutes and that the dissolution rates of APAP from the different SDs had the following order: electrospun membrane > vacuum-dried membrane ≈ freeze-dried membrane > heat-dried membrane. Electrospun nanofiber-based SDs showed markedly better dissolution-improving effects than the other SDs, mainly due to their huge surface area, high porosity resulting from web structure, and the more homogeneous distribution of APAP in the nanofiber matrix.

Preparation of core-shell PAN nanofibers encapsulated α-tocopherol acetate and ascorbic acid 2-phosphate for photoprotection

Magnesium l-ascorbic acid 2-phosphate (MAAP) and α-tocopherol acetate (α-TAc), as the stable vitamin C and vitamin E derivative, respectively, are often applied to skin care products for reducing UV damage. The encapsulation of MAAP (0.5%, g/mL) and α-TAc (5%, g/mL) together within the polyacrylonitrile (PAN) nanofibers was demonstrated using a coaxial electrospinning technique. The structure and morphology characterizations of the core-shell fibers MAAP/α-TAc-PAN were investigated by SEM, FTIR and XRD. As a negative control, the blend nanofibers MAAP/α-TAc/PAN were prepared from a normal electrospinning method. The results from SEM indicated that the morphology and diameter of the nanofibers were influenced by concentration of spinning solution, the polymer component of the shell, the carrying agent of the core and the fabricating methods, and the core-shell nanofibers obtained at the concentration of 8% had finer and uniform structure with the average diameters of 200 ± 15nm. From in vitro release studies it could be seen that both different fiber specimens showed a gradual increase in the amount of α-TAc or MAAP released from the nanofibers. Furthermore, α-TAc and MAAP released from the blend nanofibers showed the burst release at the maximum release of ∼15% and ∼40% during the first 6h, respectively, but their release amount from the core-shell nanofibers was only 10-12% during the initial part of the process. These results showed that core-shell nanofibers alleviated the initial burst release and gave better sustainability compared to that of the blend nanofibers. The present study would provide a basis for further optimization of processing conditions to obtain desired structured core-shell nanofibers and release kinetics for practical applications in dermal tissue.

Ester prodrug-loaded electrospun cellulose acetate fiber mats as transdermal drug delivery systems

Cellulose acetate (CA) fibers loaded with the ester prodrugs of naproxen, including methyl ester, ethyl ester and isopropyl ester, were prepared through electrospinning using acetone/N,N-dimethylacetamide(DMAc)/ethanol (4:1:1, v/v/v) as solvent. The chemical and morphological characterizations of the medicated fibers were investigated by means of SEM, DSC, XRD and FTIR, as well as the studies of the drug release properties. The results indicated that the morphology and diameter of the fibers were influenced by the concentration of spinning solution, applied voltage, electrospun solvent and the surfactants. The average diameters of the fibers ranged between 100 and 500xa0nm for three prodrugs. There was good compatibility between CA and three prodrugs in the blended fibers, respectively. In vitro release indicated that constant drug release from the fiber was observed over 6xa0days. The prodrugs were successfully encapsulated into the fibers, and this system was stable in terms of effectiveness in release.