Electroencapsulation and electrospraying of pharmaceutical materials in preparation for oral drug delivery applications

In bi-polar parallel nozzle electroencapsulation, two oppositely charged droplet jets are produced by electrospraying (electrostatic atomization), a method of extracting micro- or nanodroplets from a body of liquid using electrical forces. The two species of droplets are attracted to each other due to Coulombic forces. Upon contact, droplets of similar size can merge into a single-phase, or form a core-shell capsule structure, depending on the mutual miscibility of the liquids. In this work, an electroencapsulation setup was designed and experimented for the single-step production of two types of drug carrier particles of 10–50 μm in size: wrinkled, solid Eudragit L 100 enteric polymer micromatrix particles; and spherical microcapsules consisting of a solid Eudragit E 100 polymer shell and a liquid glycerol core. The carrier particle payload consisted of a model drug (griseofulvin); or griseofulvin loaded, mesoporous silicon (PSi) nano- and microparticles, which themselves are functional drug carriers. The goal was to obtain the carrier particle payloads as either stable drug dispersions in a disordered solid state, or non-agglomerated PSi nanoparticle dispersions, to enhance the drug dissolution properties at release. The carrier formulations would effectively render the payload in the form of an inert micropowder for purposes of handling and dosing. In oral administration, the formulations were to shield the payload from intestinal metabolism, and to restrain its release until arrival to target pH-conditions. The carrier particles were characterized to evaluate these properties. The micromatrix particles were proven stable and gastro-resistant in vitro. Griseofulvin dissolution and absorption properties improved significantly, the latter especially for the drug loaded PSi payloads. Finally, the efficiency of the asymmetric core-shell microcapsule production was optimized using Taguchi techniques. In conclusion, electroencapsulation was found to be a potentially feasible method to improve the oral bioavailability of poorly soluble drugs. Furthermore, partially crystalline piroxicam microparticles were produced by electrospraying, and characterized. The crystalline phase was shown to consist of a previously unknown, stable polymorphic form of piroxicam. The result suggests the method could provide a unique way to produce novel drug polymorphs. Thus, it is possible that the dissolution properties of certain drug materials could be improved sufficiently to facilitate oral administration, without the necessity to use more complex formulations

Specificity and sensitivity of the Beck Hopelessness Scale for suicidal ideation among adolescents entering early intervention service

Previous studies have shown an association between hopelessness and suicidal behaviour in clinical populations. The aim of the study was to investigate sensitivity, specificity, and predictive validity of the Beck Hopelessness Scale (BHS) for suicidal ideation in adolescents who show early risk signs on the psychiatric disorder continuum. Three-hundred and two help-seeking adolescents (mean age=15.5 years) who were entering an early intervention team at Helsinki University Central Hospital, Finland, completed questionnaires of BHS and suicidal ideation, derived from Beck Depression Inventory (BDI-II). Results suggest that a BHS cut-off score 8 (sensitivity=0.70, specificity=0.76) or cut-off score 9 (sensitivity=0.63, specificity=0.80) may be useful to detect suicidal ideation with BHS in help-seeking adolescents population. Results remain mainly the same in a separate analysis with adolescents at risk for psychosis. The results support previous cut-off points for BHS in identification of suicidal ideation. The results suggest also that lower cut-off scores may be useful in sense of sensitivity, especially in clinical settings.Peer reviewe

Electroencapsulation of Mesoporous Silicon Particles for Controlled Oral Drug Delivery

Mesoporous silicon (PSi) has lately been the focus of interest as a potential new orally dosed drug carrier in a steeply increasing number of papers, where the strengths of PSi in such applications has been shown. Perhaps most importantly, drugs will remain in an amorphous form instead of crystallizing while loaded into the pores of PSi. The advantage of this is greatly increased solubility and dissolution rate of the drug. In the present work, we investigate the possibility of enhancing the drug carrier functionality of PSi micro- and nanoparticles by encapsulating the drug loaded PSi particles in a suitable polymer capsule structure by the method of collision of oppositely charged, electrosprayed droplets. Embed-ding the PSi particles in such polymer structure of micrometer scale will not only vastly im-prove the workability of PSi nanoparticles and the smallest of microparticles, but with suit-able material choices will also potentially enable targeted release of the drug loaded PSi par-ticles to a desired part of the gastrointestinal (GI) tract. This would help towards eliminating the intestinal first-pass effect of an orally dosed drug, which together with the already advan-tageous properties of PSi would result in an increased bioavailability of the drug. The gained advantage would be significant, since it has been estimated that more than 95% of new drug candidates suffer from poor pharmacokinetic properties, resulting in poor bioavailability.</p

Synthesis and characterization of ceria-supported catalysts for carbon dioxide transformation to diethyl carbonate

Abstract The support materials Al₂O₃, SiO₂ and TiO₂ were modified with 16 wt% CeO₂, using two different preparation methods evaporation-impregnation and precipitation-deposition. The synthesized 16 wt% CeO₂-Al₂O₃, 16 wt% CeO₂-SiO₂ and 16 wt% CeO₂-TiO₂ materials were characterized by means of X-ray powder diffraction for the phase purity, scanning electron microscopy for the morphology, nitrogen physisorption to determine the specific surface area and X-ray photo electron spectroscopy for the oxidation state of the Ce in the TiO₂, Al₂O₃ and SiO₂ matrices. Transmission electron microscopy was used to study the particle size of CeO₂ whereas CO₂-temperature programmed desorption (TPD) was used to determine the basicity of ceria-modified TiO₂, Al₂O₃ and SiO₂ catalysts. Furthermore, the catalytic performance of the as prepared CeO₂-modified catalysts were compared in the synthesis of diethyl carbonate starting from ethanol and CO₂ using butylene oxide as the dehydrating agent. The physico-chemical characterization results were correlated with the catalytic activity results and discussed in detail

Controlled Dissolution of Griseofulvin Solid Dispersions from Electrosprayed Enteric Polymer Micromatrix Particles: Physicochemical Characterization and <i>in Vitro</i> Evaluation

The oral bio­avail­ability of a poorly water-soluble drug is often inadequate for the desired therapeutic effect. The bio­avail­ability can be improved by enhancing the physico­chemical properties of the drug (e.g., dissolution rate, permeation across the gastro­intestinal tract). Other approach include shielding the drug from the gastric metabolism and targeted drug release to obtain optimal drug absorption. In this study, a poorly water-soluble model drug, griseo­fulvin, was encapsulated as disordered solid dispersions into Eudragit L 100-55 enteric polymer micro­matrix particles, which were produced by electro­spraying. Similar micro­matrix particles were also produced with griseo­fulvin-loaded thermally oxidized mesoporous silicon (TOPSi) nanoparticles dispersed to the polymer micro­matrices. The <i>in vitro</i> drug dissolution at pH 1.2 and 6.8, and permeation at pH 7.4 across Caco-2/HT29 cell monolayers from the micro­matrix particles, were investigated. The micro­matrix particles were found to be gastro-resistant, while at pH 6.8 the griseo­fulvin was released very rapidly in a fast-dissolving form. Compared to free griseo­fulvin, the permeability of encapsulated griseo­fulvin across the intestinal cell monolayers was greatly improved, particularly for the TOPSi-doped micro­matrix particles. The griseo­fulvin solid dispersions were stable during storage for 6 months at accelerated conditions. Overall, the method developed here could prove to be a useful oral drug delivery solution for improving the bio­avail­ability of poorly water-soluble or otherwise problematic drugs