Structure evolution of spin-caoted phase separated EC/HPC films

Porous phase-separated films made of ethylcellulose (EC) and hydroxypropylcellulose (HPC) are commonly used for controlled drug release. The structure of these thin films is controlling the drug transport from the core to the surrounding liquid in the stomach or intestine. However, detailed understanding of the structure evolution is lacking. In this work, we use spin-coating, a widely applied technique for making thin uniform polymer films, to mimic the industrial manufacturing process of fluidized bed spraying. The aim of this work is to understand the structure evolution and phase separation kinetics of single layer and multi-layer spin-coated EC/HPC films. The structure evolution is characterized using confocal laser scanning microscopy (CLSM) and image analysis.The influence of spin-coating parameters and EC:HPC ratio on the final phase-separated structure and the film thickness was determined. Varying spin speed and EC:HPC ratio gave us precise control over the characteristic length scale and thickness of the film. The results show that the phase separation occurs through spinodal decomposition and that the characteristic length scale increases with decreasing spin speed and with increasing HPC ratio. The thickness of the spin-coated film decreases with increasing spin speed.Furthermore, optimized spin-coating parameters were selected to study the kinetics of phase separation in situ, in particular the coarsening mechanisms and the time dependence of the domain’s growth as a function of EC:HPC ratio. We identified two main coarsening mechanisms: interfacial tension driven hydrodynamic growth for the bicontinuous structure and diffusion driven coalescence for the discontinuous structures. In addition, we obtained information on the wetting, the shrinkage, and the evaporation process by looking at a film cross section, which allowed an estimation of the binodal of the phase diagram.The findings from this work give a good understanding of the mechanisms responsible for the morphology development and open the road towards tailoring thin EC/HPC film structures for controlled drug release

Structure evolution of phase-separated EC/HPC films for controlled drug release

Porous phase-separated ethylcellulose/hydroxypropylcellulose (EC/HPC) films are used to control drug transport out of pharmaceutical pellets. The drug transport rate is determined by the structure of the porous films that are formed as the water-soluble HPC leaches out. In industry, the pellets are being coated using a fluidized bed spraying device, and layered films with varying porosity and structure are obtained. A detailed understanding of the formation mechanisms of the multilayered phase-separated structure during production is lacking. Here, we have investigated EC/HPC films produced by spin-coating, which mimics the industrial manufacturing process in a reproducible and well-controlled manner. This work is aimed to understand\ua0 why the\ua0 film structure is layered, and why it exhibits different\ua0 porosities and structures by understanding the film formation mechanisms. The 2D and 3D structures of the EC/HPC films were characterized using confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM), focused ion beam SEM (FIB-SEM) and image analysis. The thickness of the films was measured by profilometry.To be able to understand the multilayer formation, we first studied the structure evolution in EC/HPC monolayer films. The effect of the EC/HPC ratio (from 15 to 85 wt% HPC) on the in-plane and cross-sectional structure evolution was determined. Bicontinuous structures were found for 30 to 40 wt% HPC and discontinuous structures were found for the fractions 15 to 22 and 45 to 85 wt% HPC. The growth of the characteristic length scale followed a power law, , with \ua0for bicontinuous structures, and \ua0 \ua00.45 - 0.75 for discontinuous structures. An image analysis method to characterize the time-dependent 2D curvature evolution was developed. Two main coarsening mechanisms could be identified: interfacial tension-driven hydrodynamic growth for bicontinuous structures and diffusion-driven coalescence for discontinuous structures. The cross-sectional structure evolution shows that during shrinkage of the film, the phase-separated structure undergoes a transition from 3D to nearly 2D structure evolution along the surface. The shrinkage rate was found to be independent of the EC/HPC ratio. A new method to estimate part of the binodal curve in the ternary phase diagram for EC/HPC in ethanol has been developed. For multilayer films, the results showed that the inherent behaviour of the monolayer films have a strong impact on the formation of each new layer in multilayer films. A gradient in structure size with larger structures close to the substrate and smaller structures close to the air surface was found and explained by the redissolution of the layers already deposited during previous deposition cycles. By varying the EC/HPC ratio during the multilayer film production, we showed in situ that the layers do not mix. By varying the spin speed every other layer, we produced a layered film exhibiting varying porosity, proposing a possible explanation for obtaining a layered coating in the industrial process. The findings of this work provide a good understanding of the mechanisms responsible for the morphology development and enable tailoring of multilayer EC/HPC films structure for controlled drug release

Noniterative approach to the total asymmetric synthesis of 15-carbon polyketides and analogs with high stereodiversity

Starting from inexpensive furan and furfuryl alcohol, a noniterative approach to the synthesis of pentadeca-1,3,5,7,9,11,13,15-octols and their derivatives has been developed. The method relies upon the double [4+3]-cycloaddition of 1,1,3-trichloro-2-oxylallyl cation with 2,2'-methylenedifuran and conversion of the adducts into meso and (±)-threo-1,1'-methylenebis (cis- and trans-4,6-dihydroxycyclohept-1-ene) derivatives. The latter undergo oxidative cleavage of their alkene moieties, generating 5-hydroxy-7-oxoaldehydes that are reduced diastereoselectively into either syn or anti-5,7-diols. Asymmetry is realized using either chiral desymmetrization with Sharpless asymmetric dihydroxylation or by kinetic resolution of polyols using lipase-catalyzed acetylations. All of the possible stereomeric pentadeca-1,3,5,7,9,11,13,15-octols and derivatives can be obtained with high stereoselectivity applying simple operations, thus demonstrating the high stereodiversity of this new, noniterative approach to the asymmetric synthesis of long-chain polyketide

Disseminating health evidence summaries to increase evidence use in health care

OBJECTIVE: To verify whether an intervention based on disseminating health evidence summaries by e-mail to health professionals increases access to health evidence databases, and whether health professionals intend to apply the evidence received by e-mail in their clinical practice. METHODS: This quantitative study started with a survey to collect demographic data and patterns of access to health evidence databases. It was followed by a longitudinal intervention, over 48 weeks, that disseminated 143 health evidence summaries to 339 health professionals with higher education degree who work in the Brazilian Unified Health System. In the longitudinal intervention phase, health professionals voluntarily assessed the received health evidence summaries using the information assessment method. Finally, the study concluded with a survey to identify changes in accessing health evidence databases. RESULTS: Of the 339 Brazilian health professionals participating in this research, 90 (26.5%) answered the initial and final surveys. After 48 weeks, there was an increase in the use of health evidence databases; 186 (54.9%) participants submitted 7,942 assessments of health evidence summaries, which were relevant for patient care in 5,409 (68%) assessments. CONCLUSIONS: The dissemination of health evidence summaries by e-mail to health professionals in Brazil increases the reported use of evidence in clinical practice

Glyceraldehyde as an efficient chemical crosslinker agent for the formation of chitosan hydrogels

The rheological changes that occur during the chemical gelation of semidilute solutions of chitosan in the presence of the low‐toxicity agent glyceraldehyde (GCA) are presented and discussed in detail. The entanglement concentration for chitosan solutions was found to be approximately 0.2 wt.% and the rheological experiments were carried out on 1 wt.% chitosan solutions with various amounts of GCA at different temperatures (25 \ub0C and 40 \ub0C) and pH values (4.8 and 5.8). High crosslinker concentration, as well as elevated temperature and pH close to the pKa value (pH ≈ 6.3–7) of chitosan are three parameters that all accelerate the gelation process. These conditions also promote a faster solid‐like response of the gel‐network in the post‐gel region after long curing times. The mesh size of the gel‐network after a very long (18 h) curing time was found to contract with increasing level of crosslinker addition and elevated temperature. The gelation of chitosan in the presence of other chemical crosslinker agents (glutaraldehyde and genipin) is discussed and a comparison with GCA is made. Small angle neutron scattering (SANS) results reveal structural changes between chitosan solutions, incipient gels, and mature gels