Inkjet printing of a thermolabile model drug onto FDM-printed substrates: formulation and evaluation.

OBJECTIVE: The inkjet printing (IP) and fused deposition modeling (FDM) technologies have emerged in the pharmaceutical field as novel and personalized formulation approaches. Specific manufacturing factors must be considered in each adopted methodology, i.e. the development of suitable substrates for IP and the incorporation of highly thermostable active pharmaceutical compounds (APIs) for FDM. In this study, IP and FDM printing technologies were investigated for the fabrication of hydroxypropyl methylcellulose-based mucoadhesive films for the buccal delivery of a thermolabile model drug. Significance: This proof-of-concept approach was expected to provide an alternative formulation methodology for personalized mucoadhesive buccal films. METHODS: Mucoadhesive substrates were prepared by FDM and were subjected to sequential IP of an ibuprofen-loaded liquid ink. The interactions between these processes and the performance of the films were evaluated by various analytical and spectroscopic techniques, as well as by in vitro and ex vivo studies. RESULTS: The model drug was efficiently deposited by sequential IP passes onto the FDM-printed substrates. Significant variations were revealed on the morphological, physicochemical and mechanical properties of the prepared films, and linked to the number of IP passes. The mechanism of drug release, the mucoadhesion and the permeation of the drug through the buccal epithelium were evaluated, in view of the extent of ink deposition onto the buccal films, as well as the distribution of the API. CONCLUSIONS: The presented methodology provided a proof-of-concept formulation approach for the development of personalized mucoadhesive films.

A study on the synchronous decoration of molybdenum oxide or tungsten oxide nanoparticles on anode materials for natural gas fed solid oxide fuel cells using ultrasounds.

Sonochemistry was used for the metal oxides nanoparticle synthesis. All experiments were run using a BANDELIN Sonopuls HD 3200 ultrasonic generator (20 kHz, 200 W net output) with a ultrasonic probe in thermostated environment of 80 °C under ambient air. At the same time, ultrasonication activity achieved their decoration on state-of-the-art fuel cell anode powders. These modified powders shall be used in solid oxide and ceramic proton exchange membrane fuel cells anode sites. Metal oxide nanoformations synthesized were those of tungsten and molybdenum. In case of sonochemical synthesis, organometallic compounds dissolved in organic solvents played the role of precursors. Experiments of metal oxides synthesis revealed that ultrasonication intensity and solvents are able to affect final nanoparticles size distribution and morphology. At the same time, ratio of precursor and substrate compounds amounts as well as ultrasonication intensity and duration were all found to affect the decoration loading extent of nanoformations on substrates. Transmission electron microscopy was mainly used for identifying the final product of each synthesis attempt. Moreover, selected area diffraction of characteristic formations examined, gave important information about the nanocrystallinity and stoichiometry of all materials synthesized.

Physicochemical characterization of sterilized muds for pharmaceutics/cosmetics applications.

Clays and muds have been used for centuries as cosmetics or pharmaceutical products for various therapies. The suitability of muds and clays for health- and beauty-related applications depends on their physicochemical properties, mineralogical composition, particle characteristics and toxicity. In this work, the physicochemical characterization of 12 mud specimens from different natural spa resorts in Greece and one from Israel (Dead Sea) is presented. All specimens were sterilized at 121 °C for 20 min, because of their intended use. The Greek mud specimens were collected from various locations in Macedonia, Western Greece and Northeast Aegean. All muds were characterized concerning their mineralogical, chemical components as well as their morphological characteristics using appropriate methods [powder X-ray diffraction (XRD), thermogravimetric analysis (TGA), nitrogen absorption specific surface area measurements (BET), scanning electron microscopy and energy dispersive X-ray spectroscopy]. The concentrations of F-, Cl-, NO3- and SO42- anions at equilibrium with the mud specimens were measured by ion chromatography. Total calcium concentration was measured using atomic absorption spectroscopy, and the concentration of total N, C, H and S in the solids was measured using elemental analysis. Moreover, total phenolic concentration (TPC) in distilled water equilibrated with the mud specimens was measured as an index for their antioxidant properties. Several muds were found to present high TPC. Several of the examined mud specimens were found to have the potential use as pharmaceuticals or cosmetics. Based on the physicochemical characteristics of the mud specimens examined, possible improvement in their use and applicability has been suggested.

Development of a new combined test setup for accelerated dynamic pH-controlled in vitro calcification of porcine heart valves.

Fifty years after their first implantation, bioprosthetic heart valves still suffer from tissue rupture and calcification. Since new bioprostheses exhibit a lower risk of calcification, fast and reliable in vitro methods need to be evaluated for testing the application of new anti-calcification techniques. This report describes a modification of the well-known in vitro dynamic calcification test method (Glasmacher et al, Leibniz University Hannover (LUH)), combined with the pH-controlled, constant solution supersaturation (CSS) method (University of Patras (UP)). The CSS method is based on monitoring the pH of the solution and the addition of calcium and phosphate ion solutions through the implementation of two syringe pumps. The pH and the activities of all ions in the solutions are thus kept constant, resulting in higher calcification rates compared to conventional in vitro methods in which solution supersaturation is allowed to decrease without any further control. To verify this hypothesis, five glutaraldehyde preserved porcine aortic valves were tested. Three of the valves were tested according to a free-drift methodology: the valves were immersed in a supersaturated calcification solution, with an initial total calcium times total phosphate product of (CaxP)=10.5 (mmol/L)2, renewed weekly. Two valves were tested by the new pH-controlled loop system, implementing the CSS methodology. All valves were tested for a 4-week period, loaded at 300 cycles per minute, resulting in a total of 12 million cycles at the end of the testing period. The degree of calcification was determined weekly by means of mux-ray, and by conventional, clinical and micro-computer tomography (CT, muCT). The results showed that the valves mineralizing at constant solution supersaturation in vitro yielded higher rates of calcification compared to the valves tested at conditions of decreasing solution supersaturation without any control, indicating the development of a new, accelerated, controllable in vitro calcification method.

Application of anodic stripping voltammetry for zinc, copper, and cadmium quantification in the aqueous humor: implications of pseudoexfoliation syndrome.

Anodic stripping voltammetric (ASV) procedure, using mercury film electrode, was optimized and applied to determine the concentrations of zinc, cadmium, and copper in the aqueous humor. Concentration levels as low as 1 ppb of the test metals was possible to be detected using short electrolysis times (120 s) and microquantities of aqueous humor (up to 35 µL). As a first application of the voltammetric analysis of trace metals in the aqueous humor, the role of the three selected trace elements in the pseudoexfoliation (PEX) syndrome was examined. Samples from aqueous humor were collected during cataract extraction from patients with and without PEX. The zinc and copper concentration levels in the aqueous humor did not show statistically significant difference in the study and control group. Cadmium was detected in a small number of samples, without however statistical differences between the two groups. ASV proved to be a highly precise and sensitive tool for the quantification of heavy metal ions in aqueous humor. Further studies may lead to useful conclusions for the role of zinc, copper, or cadmium in PEX syndrome.

Opacification of hydrophilic acrylic intraocular lens attributable to calcification: investigation on mechanism.

PURPOSE: To identify the nature and to investigate the biochemical mechanisms leading to late opacification of implanted hydrophilic acrylic intraocular lenses (IOLs). DESIGN: Retrospective laboratory investigation. METHODS: setting: Department of Ophthalmology, Medical School, Department of Chemical Engineering, Laboratory of Inorganic and Analytical Chemistry, University of Patras and FORTH-ICEHT, Greece. study population: Thirty IOLs were explanted one to 12 years postimplantation attributable to gradual opacification of the lens material. observation procedures: Materials analysis was done using scanning electron microscopy (SEM) equipped with a microanalysis probe (EDS), confocal microscopy, x-ray diffraction (XRD), and Fourier transform infrared (FTIR) for the identification of the substances involved in the opacified lenses. RESULTS: SEM investigation showed plate-like as well as prismatic nanoparticle deposits of calcium phosphate crystallites on the surface and in the interior of opacified IOLs. The plate-like deposits exhibited morphology and particle size typical for octacalcium phosphate (OCP), while the respective characteristics of the prismatic nanocrystals were typical of hydroxyapatite (HAP). EDS analysis confirmed the chemical composition of the deposits. Aqueous humor analysis showed that the humor is supersaturated with respect to both OCP and HAP, favoring the formation of the thermodynamically more stable HAP, while the formation and kinetic stabilization of other transient phases is also very likely. In vitro experiments using polyacrylic materials confirmed the clinical findings. CONCLUSIONS: Hydrophilic acrylic IOLs' opacification may be attributed to the deposition of calcium phosphate crystallites. HAP is the predominant crystalline phase of these crystallites. Surface hydroxyl groups of the polyacrylic materials facilitate surface nucleation and growth.

The interaction of diphosphonates with calcitic surfaces: understanding the inhibition activity in marble dissolution.

The rates of dissolution of calcitic Carrara marble have been reported to be significantly reduced in alkaline pH (pH 8.25) at 25 degrees C in the presence of (1-hydroxyethylidene)-1,1 diphosphonic acid (HEDP). The adsorption takes place at the calcite/water interface at the double layer through the interaction of charged surface species with the charged solution species of the adsorbate. The present work focused on obtaining a better understanding of the interaction of the calcite surface with HEDP. Calculations were performed according to the triple layer model, assuming the formation of surface complexes between the charged surface species of calcite and the species of HEDP dominant at pH 8.25. According to the model, the adsorbed species are located at the inner Helmholtz plane of the electrical double layer. Strong lateral interactions between the adsorbed species were suggested and were corroborated from the calculation of the respective energy, which was equal to 69 kJ mol(-1). The adsorption isotherm was consistent with the proposed model at low surface coverage values, while discrepancies between the values experimentally measured and the predicted were found at higher adsorbate concentrations. The deviations from the predicted values were attributed to the fact that HEDP adsorption on calcite resulted in the formation of multiple layers. The model explained adequately the changes in the zeta-potential values of calcite in the presence of HEDP in the solution which resulted in charge reversal upon adsorption.