S.W. Annie Bligh

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.

Dual drug release nanocomposites prepared using a combination of electrospraying and electrospinning

In this paper we demonstrate for the first time that structural nanocomposites providing dual drug release can be generated using a combination of electrospraying and electrospinning. Ketoprofen (KET) was used as a model drug, and polyvinylpyrrolidone (PVP) and Eudragit® L100-55 (EL100) respectively taken as the sheath and core matrices to prepare the nanofibers. Scanning and transmission electron microscope observations demonstrated that the nanofibers had smooth surfaces and cross-sections, and distinct core–sheath nanostructures. They also had relatively uniform diameters of 0.64 ± 0.21 μm. Differential scanning calorimetry and X-ray diffraction results indicated that the nanofibers contained KET homogeneously distributed in both the sheath and core parts of the fibers. IR spectra indicated that this molecular dispersion was likely to be a result of hydrogen bonding between the components. In vitro dissolution tests showed that the core–sheath fibers provided dual drug release profiles with an immediate release of 35.1% in acidic solutions and sustained release of 62.2% in a pH 6.8 phosphate buffer. The strategy developed here significantly expands the applications of electrohydrodynamic atomization processes in producing novel structural nanocomposites for complex and time-programmed drug release profiles.

Comprehensive two-dimensional high-performance liquid chromatography system with immobilized liposome chromatography column and reversed-phase column for separation of complex traditional Chinese medicine Longdan Xiegan Decoction.

A comprehensive two-dimensional HPLC system with an immobilized liposome chromatography (ILC) column in conjunction with an RP column (in tandem) was developed for the screening and analysis of the membrane-permeable compounds in a traditional Chinese medicine prescription Longdan Xiegan Decoction (LXD). More than 50 components in LXD were resolved using the developed separation system. Eight flavonoids and two iridoids were identified interacting with the ILC column; a system that mimics biomembranes. The results show that the developed comprehensive two-dimensional chromatography system can be used for identifying membrane permeable natural products in complex matrixes such as extracts of traditional Chinese medicine prescriptions.

Electrospun pH-sensitive core–shell polymer nanocomposites fabricated using a tri-axial process

UNLABELLED A modified tri-axial electrospinning process was developed for the generation of a new type of pH-sensitive polymer/lipid nanocomposite. The systems produced are able to promote both dissolution and permeation of a model poorly water-soluble drug. First, we show that it is possible to run a tri-axial process with only one of the three fluids being electrospinnable. Using an electrospinnable middle fluid of Eudragit S100 (ES100) with pure ethanol as the outer solvent and an unspinnable lecithin-diclofenac sodium (PL-DS) core solution, nanofibers with linear morphology and clear core/shell structures can be fabricated continuously and smoothly. X-ray diffraction proved that these nanofibers are structural nanocomposites with the drug present in an amorphous state. In vitro dissolution tests demonstrated that the formulations could preclude release in acidic conditions, and that the drug was released from the fibers in two successive steps at neutral pH. The first step is the dissolution of the shell ES100 and the conversion of the core PL-DS into sub-micron sized particles. This frees some DS into solution, and later the remaining DS is gradually released from the PL-DS particles through diffusion. Ex vivo permeation results showed that the composite nanofibers give a more than twofold uplift in the amount of DS passing through the colonic membrane as compared to pure DS; 74% of the transmitted drug was in the form of PL-DS particles. The new tri-axial electrospinning process developed in this work provides a platform to fabricate structural nanomaterials, and the core-shell polymer-PL nanocomposites we have produced have significant potential applications for oral colon-targeted drug delivery. STATEMENT OF SIGNIFICANCE A modified tri-axial electrospinning is demonstrated to create a new type of core-shell pH-sensitive polymer/lipid nanocomposites, in which an electrospinnable middle fluid is exploited to support the un-spinnable outer and inner fluids. The structural nanocomposites are able to provide a colon-targeted sustained release and an enhanced permeation performance of diclofenac sodium. The developed tri-axial process can provide a platform for fabricating new structural nanomaterials with high quality. The strategy of a combined usage of polymeric excipients and phospholipid in a core-shell format should provide new possibilities of developing novel drug delivery systems for efficacious oral administration of poorly-water soluble drugs.

Characterization of fifty‐one flavonoids in a Chinese herbal prescription Longdan Xiegan Decoction by high‐performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry and photodiode array detection

High-performance liquid chromatography coupled to electrospray ionization (ESI) tandem mass spectrometry and photodiode array detection (HPLC-DAD-ESI-MS(n)) was developed to identify and characterize the flavonoids in a Chinese formulated preparation, Longdan Xiegan Decoction (LXD). In total, fifty-one flavonoids (27 flavones, 10 flavanones, 7 chalcones, 5 flavonols and 2 isoflavones) were characterized. Eighteen compounds among them including a newly detected flavonoid, naringin, from the ingredient herbs, were unambiguously determined by comparing the retention times (t(R)), UV spectral data and mass fragmentation behaviors with those of the reference compounds. Another thirty-three compounds were tentatively identified by referencing to the reported data of their UV and MS spectra. The ESI-MS/MS fragmentation behavior of flavones (OMe-substituted, O-glycosides, C-glycosides), chalcones, flavonols and their appropriate characteristic pathways were proposed. In negative ion ESI-MS all the flavonoids yielded prominent [M--H](-) ions in the first order mass spectra. Fragmentation with a loss of mass of 15 Da (CH(3)), 18 Da (H(2)O), 28 Da (CO), 44 Da (CO(2)), 56 Da (2CO) and the residues of glucose and glucuronic acid observed in the MS/MS spectra were useful for aiding the structural identification of the flavonoids investigated.

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 130 ±10 nm 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).

Neutral gadolinium(III) complexes of bulky octadentate dtpa derivatives as potential contrast agents for magnetic resonance imaging

A series of bulky and neutral gadolinium complexes of [bis(R-amide)dtpaH3] (where R = Pri,, Bui,, Bz and phenylethyl, L1--L4)) with potential application as contrast agents for magnetic resonance imaging has been prepared and characterized ; the relaxivity of these complexes is comparable to the contrast agent [Gd(dtpa)(H2OO)]; which is which is currently used in clinics; the X-ray structure analysis of the gadolinium(III) complex of L3 reveals a neutral nine-coordinate complex featuring a water molecule in the tricapped trigonal prismatic metal coordination sphere.

Self-assembled liposomes from amphiphilic electrospun nanofibers

Amphiphilic nanofibers composed of the hydrophilic polymer polyvinylpyrrolidone K60 (PVP) and soybean lecithin were fabricated using an electrospinning process. As a result of the templating and confinement properties of the nanofibers, phosphatidyl choline (PC) liposomes were spontaneously formed through molecular self-assembly when the fibers were added to water. The sizes of the self-assembled liposomes could be manipulated by varying the content of PC in the nanofibers (over the range 9.1–33.3% (w/w) in the present study). The influence of PC on nanofiber formation, and a possible mechanism of templated liposome formation are discussed. This facile and convenient strategy for manipulating molecular self-assembly to synthesize liposomes provides a versatile new approach for the development of novel drug delivery systems and biomaterials.

Identification of metabolites of geniposide in rat urine using ultra‐performance liquid chromatography combined with electrospray ionization quadrupole time‐of‐flight tandem mass spectrometry

Geniposide, an iridoid glycoside, is an important and characteristic compound in the fruits of Gardenia jasminoides Ellis, a commonly used medicinal herb in Chinese traditional and folk medicine for the treatment of inflammation and jaundice. However, few studies have been carried out on the metabolism of geniposide. In this study, we have established a rapid and sensitive method using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC/ESI-QTOF-MS) for analysis of the metabolic profile of geniposide in rat urine after oral administration. A total of ten metabolites were detected and identified by comparing their fragmentation patterns with that of geniposide using Metabolynx™ and MassFragment™ software tools. The results revealed that the principal metabolism pathways of geniposide in rat occurred after deglycosylation of the irdoid glycoside take place and this is followed by glucuronidation and the pyran-ring cleavages. The major metabolite, the glucuronic acid conjugate of genipin as observed in vivo, was further confirmed by the in vitro enzymatic study. The results of this work have demonstrated the feasibility of the UPLC/ESI-QTOF-MS approach for rapid and reliable characterization of metabolites from iridoid compounds.

HPLC fingerprints combined with principal component analysis, hierarchical cluster analysis and linear discriminant analysis for the classification and differentiation of Peganum sp. indigenous to China

INTRODUCTION Seeds of wild Peganum harmala Linn., P. multisectum (Maxim) Bobr., P. nigellastrum Bunge and a probable indeterminate species, herein referred to as P. variety, are commonly used in Chinese medicine. These seeds cannot be differentiated based on morphology. OBJECTIVE Seeds of P. harmala Linn., P. multisectum (Maxim) Bobr., P. nigellastrum Bunge and P. variety were collected in different provinces in China and their HPLC profiles were recorded for statistical analysis and pattern recognition.Methodology - HPLC chromatograms of seed extracts were recorded under the same conditions. Individual HPLC chromatograms for each species were evaluated against the mean chromatogram for the same species generated using a similarity evaluation computer program. Data from chromatographic fingerprints were also processed using principal component analysis (PCA), hierarchical cluster analysis (HCA) and linear discriminant analysis (LDA). RESULTS The Peganum sp. seed extracts had similar HPLC fingerprints but with some inter-specific differences. The chromatographic fingerprints combined with PCA, HCA and LDA could distinguish the seeds of the different species of Peganum investigated. CONCLUSION HPLC fingerprints can be used to authenticate and differentiate the seeds of three different species of genus Peganum indigenous to China. The results indicated that the unidentified P. variety might indeed be a new species or variety.