Study of types and mixture ratio of organic solvent used to dissolve polymers for preparation of drug-containing PLGA microspheres

The effects of the types and the ratios of various organic solvents used as a mixtures to dissolve poly (lactide-co-glycolide) (PLGA) by using a solvent evaporation method, a technique used to prepare polymer particles, were carefully studied in order to investigate their advantages in developing drug delivery system (DDS) formulations for the prepared microspheres. The particle size and drug loading efficiency of drug-containing PLGA microspheres were found to be dependent on the types of solvent used due to the interfacial tension between the organic solvent and water phase. The drug loading efficiency of monodisperse microspheres prepared by using a membrane emulsification technique employing organic solvents and high interfacial tension for dissolving the PLGA was increased in a controlled manner. The organic solvents with high interfacial tension in the water phase used for the preparation of polymer particles by means of the solvent evaporation method were found to be suitable in terms of improvement in the properties of DDS formulations.     

Surfactive water-soluble copolymers for the preparation of controlled surface nanoparticles by double emulsion/solvent evaporation

We have already shown that polylactide (PLA) nanoparticles covered with a hydrophilic polymeric layer can be prepared by simple emulsion/solvent evaporation by using amphiphilic copolymers as surfactants during the procedure. The external layer is then constituted by the hydrophilic part of the macromolecular surfactant. This kind of nanospheres is useful for the encapsulation of lipohilic molecules. The use of amphiphilic copolymers as surfactants in the preparation of PLA nanospheres with controlled surface properties, was then applied to the double emulsion/solvent evaporation procedure. The aim was to allow the encapsulation of water-soluble bioactive molecules in PLA particles with controlled surface properties. In this paper, we describe the results obtained with three different water-soluble monomethoxypolyethylene oxide (MPEO)-b-PLA diblock copolymers used as surfactants in the preparation of nanoparticles by double emulsion/solvent evaporation. After organic solvent evaporation, the obtained nanospheres were proved to be really covered by a MPEO layer whose characteristics were determined. It was firstly shown that the MPEO-covered particles did not flocculate at 25 degrees C, even in 4 M NaCl while suspensions of bare nanospheres were destabilized for a NaCl concentration as low as 0.04 M. On the other hand, the suspensions of MPEO-covered nanoparticles in 0.3 M Na2SO4 were found to be very sensitive to temperature as they flocculated at a temperature lying between 45 and 55 degrees C depending on the MPEO-b-PLA composition. This property was attributed to the fact that MPEO is a polymer with a low critical solution temperature. The concentration of MPEO at the nanoparticle surface was then calculated for the three kinds of particles, from the initial flocculation temperature, and was found to be comparable to the value determined directly.     

Development of novel fast-disintegrating tablets by direct compression using sucrose stearic acid ester as a disintegration-accelerating agent

It was attempted to produce novel furosemide (FS) fast-disintegrating tablets by direct compression. The combination of FS, microcrystalline cellulose, croscarmellose sodium and xylitol was used as the basic formulation, and sucrose stearic acid ester (SSE) was chosen as an additional additive. The tablets with SSE were prepared by the simple addition of SSE, using a lyophilized mixture of FS and SSE or using a FS/SSE mixture obtained by evaporation of their ethanol solution. Only the tablets, produced using the FS/SSE mixture obtained by organic solvent (ethanol) evaporation, showed hardness of more than 30 N and a disintegration time of less than 20 s, which were the properties suitable for fast-disintegrating tablets. These properties were considered to result from well-mixed and fine-powdered SSE and FS.     

Characteristics of thin cellulose ester films spin-coated from acetone and ethyl acetate solutions

Spin-coated films of cellulose acetate (CA), cellulose acetate propionate (CAP), cellulose acetate butyrate (CAB) and carboxymethylcellulose acetate butyrate (CMCAB) have been characterized by ellipsometry, atomic force microscopy (AFM) and contact angle measurements. The films were spin-coated onto silicon wafers, a polar surface. Mean thickness values were determined by means of ellipsometry and AFM as a function of polymer concentration in solutions prepared either in acetone or in ethyl acetate (EA), both are good solvents for the cellulose esters. The results were discussed in the light of solvent evaporation rate and interaction energy between substrate and solvent. The effects of annealing and type of cellulose ester on film thickness, film morphology, surface roughness and surface wettability were also investigated. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Utility of mixture of commercially available polymers as constituents of sustained-release microcapsules containing cefadroxil or theophylline.

Hydroxy propyl methyl cellulose acetate succinate high grade (AS-HG) and ethyl cellulose (EC) mixture microcapsules containing cefadroxil or theophylline were prepared by a solvent evaporation method in liquid paraffin dissolved sorbitan tri-stearate as a dispersing agent, and their sustained-release properties were evaluated. The microcapsules prepared with AS-HG:EC (in a 2:5 weight ratio) mixture containing 20% of cefadroxil or theophylline exhibited apparent zero-order releasing pattern in pH 6 to 8, at 50 rpm and 37 degrees C (paddle method). These microcapsules were administered orally to beagle dogs and the plasma concentrations of cefadroxil or theophylline were measured periodically. As a result of in vivo investigation, a satisfactory sustained-release plasma pattern and an apparent zero-order process in the gastrointestinal absorption were confirmed by deconvolution analysis of both drugs.     

Thermal and mechanical properties of chitosan nanocomposites with cellulose modified in ionic liquids

In this paper, ionic liquid treatment was applied to produce nanometric cellulose particles of two polymorphic forms. A complex characterization of nanofillers including wide-angle X-ray scattering, Fourier transform infrared spectroscopy, and particle size determination was performed. The evaluated ionic liquid treatment was effective in terms of nanocrystalline cellulose production, leaving chemical and supermolecular structure of the materials intact. However, nanocrystalline cellulose II was found to be more prone to ionic liquid hydrolysis leading to formation larger amount of small particles. Each nanocrystalline cellulose was subsequently mixed with a solution of chitosan, so that composite films containing 1, 3, and 5% mass/mass of nanometric filler were obtained. Reference samples of chitosan and chitosan with micrometric celluloses were also solvent casted. Thermal, mechanical, and morphological properties of films were tested and correlated with properties of filler used. The results of both, tensile tests and thermogravimetric analysis showed a significant discrepancy between composites filled with nanocrystalline cellulose I and nanocrystalline cellulose II.     

Phase inversion cellulose acetate membranes for suppression of protein interferences in anodic stripping voltammetry 2(1). Improvement of the membrane preparation procedure

Phase inversion (PI) cellulose acetate membranes were cast on glassy carbon electrodes from a solution containing acetone as solvent and aqueous magnesium perchlorate as pore former. It is shown that a significant improvement of the reproducibility and permselective properties of the membrane is obtained by allowing complete evaporation of the solvent in a controlled humidity environment before the membrane is gelated. By using cadmium and lead as test analytes and differential pulse anodic stripping voltammetry as the detection method, it was found that the modification of the electrode greatly reduces the interference from albumin, lysozyme, gelatin and polyethylene glycol (MW 6000). The permselectivity of the PI membrane can be controlled by varying the amount of magnesium perchlorate in the casting solution and the relative humidity during the pre-gelation conditioning of the membrane.     

Development of PEG-PLA/PLGA microparticles for pulmonary drug delivery prepared by a novel emulsification technique assisted with amphiphilic block copolymers

We developed a novel "spray dry-based" method for preparing surface-modified particle via "block copolymer-assisted" emulsification/evaporation for pulmonary drug delivery. The method included three steps: (1) o/w emulsion containing both hydrophobic polymers and amphiphilic block copolymers was obtained by emulsification of water and a polymer-containing organic solvent, (2) the o/w emulsion was misted with a nebulizer, and (3) the emulsion mists were dried by a heater. In this way, the hydrophobic polymers and the hydrophobic part of the amphiphilic block copolymers gradually tangled during the evaporation of organic solvents from the o/w emulsion. Consequently, the hydrophilic polymer chain was introduced on the particle surface. The particle surface can be easily modified although there are no reactive groups in the hydrophobic polymer molecules. We successfully obtained dry PEG-PLA/PLGA microparticles by controlling the weight ratio of the block copolymer and the hydrophobic polymer. The introduction of PEG to the particle surface involves an increase in the Zeta potential of the particles. Interestingly, the "dimpled" microparticles having a diameter of approximately 2 μm were obtained. The "dimpled" microparticles can serve as drug carriers for pulmonary drug delivery, because the particles have a large surface area. We expect that this novel surface-modification technique will enable efficient fabrication of particles in drug delivery systems.     

Highly monodisperse conjugated polymer particles synthesized with drop-based microfluidics

A facile method for preparing highly monodisperse, sub-micrometre conjugated polymer particles is reported. The particles are prepared through emulsification of a conjugated polymer solution on a microfluidic chip followed by solvent evaporation. The particle size is tuned between 150 nm to 2 μm, by controlling the polymer concentration.     

Functionalized Biodegradable Nano- and Microspheres for Medical Applications

Summary: This minireview describes strategies for preparation of biodegradable (from polylactides, and poly(ε-caprolactone) and from their derivatives) nano- and microspheres for medical applications, in particular for drug delivery. In addition to standard methods of particles' formation by emulsification of polymer solution in water-miscible organic solvent with subsequent solvent evaporation or extraction there are described methods of particles formation by self assembly of polymer macromolecules, by dialysis of polymer solutions in organic water-miscible solvents carried on against water and by dispersion ring-opening polymerization of heterocyclic monomers. Strategies for encapsulation of bioactive compounds into nano- and microspheres are presented.     

Unconventional Reactivity of Cellulose Dissolved in Ionic Liquids

Summary: Ionic Liquids (IL) were applied as solvent and reaction medium in the field of homogeneous cellulose chemistry. Whereas investigations on tosylation and nucleophilic displacement reactions lead to unexpected products the application of the Huisgen reaction was successful. The standard conditions for tosylation of cellulose using the IL 1-ethyl-3-methylimidazolium acetate (EMImAc) as solvent lead exclusively to cellulose acetate, due to activation of the acetate ion of the IL by forming a mixed anhydride with p-toluenesulfonyl chloride. Further investigations showed that the anions of EMImAc and 1-ethyl-3-methylimidazolium chloride (EMImCl) are able to act as nucleophiles, thus substituting tosyl groups of tosylcellulose and forming unexpected products. Using EMImAc as solvent first to third generation propargyl-polyamidoamine (PAMAM) dendrons were attached to 6-azido-6-deoxy cellulose (degree of substitution, DS 0.75) utilising the copper catalysed Huisgen reaction leading to novel dendronized cellulose derivatives with DS values of up to 0.60. Detailed structure characterisation of the products, including elemental analysis, FTIR and NMR spectroscopy, indicates that the synthesis approach leads to products without impurities or remaining IL.     

A new method for cellulose membrane fabrication and the determination of its characteristics

A novel method to fabricate semipermeable cellulose membranes based on cellulose regeneration of a dry membrane cast by the neutralization reaction is presented in this paper. In this method, an environmentally acceptable cellulose dissolution procedure is employed to prepare the membrane casting solution comprised of microcrystalline cellulose dissolved in aqueous NaOH. Moreover, a new cast drying/cellulose regeneration technique is proposed and successfully applied to prepare membranes after the exploitation of the conventional immersion precipitation method, which results in the formation of granular cellulose particles rather than membranes due to the low cellulose concentration (<5 wt%) in the cast. In the present technique, the cellulose concentration in the membrane cast is dramatically increased through water evaporation, and glycerin is utilized in the cellulose regeneration process to achieve a gentle neutralization reaction. As a result, defect-free membranes with a uniform structure are developed. A detailed investigation is also presented concerning the effects of membrane forming parameters, i.e., the concentrations of cellulose, solvent, and acid, and the membrane thickness, on membrane properties. In addition, by coordinating the molecular separation experiments via the ultrafiltration process against a number of macromolecules with various molecular weights, the fabricated membranes are demonstrated to be capable of sieving molecules with a MW above 50,000.     

药用微胶囊的制备

微胶囊技术是21世纪重点研究开发的高新技术之一,用途广泛。本文综述了微胶囊的制备原理及方法,着重阐述了采用超临界二氧化碳技术和溶剂蒸发法制备药物微胶囊的最新研究进展,介绍了超临界流体快速膨胀(RESS)法、超临界流体抗溶剂(SAS)法和气体饱和溶液微粒制备(PGSS)法的特点,总结了溶剂蒸发法制备微胶囊的原理和溶剂蒸发法制备药物微胶囊的工艺研究现状,分析了药物微胶囊的表征方法及性能,并对今后微胶囊技术的发展作了展望。     

In vitro dissolution of uranyl acetate using different methods

The dissolution rate of a material in the lung is an important parameter in evaluating the risk to humans following accidental inhalation of a substance and is also a parameter that may be useful in characterizing particles for nuclear forensics analysis. Conventional methods of measuring dissolution rates in vitro involve exposing the material or particles to a solvent, such as water, saline, or solutions that simulate lung fluid, and measuring the fraction of material that dissolves with time. A new device for measuring dissolution rates for small samples, especially individual particles, was evaluated that incorporates a regenerated cellulose dialysis membrane fixed to the bottom of a small, 2 mL plastic cup that fits into the top of a 50 mL plastic centrifuge tube. The cup is easily transferred among a series of tubes containing solvent to measure rate of dissolution. The dialysis membrane has a diffusion rating of 20 kDa molecular weight cut off which greatly exceeds the size of the dissolved uranium molecule. The performance of the dialysis cup device was evaluated by measuring the dissolution rate of uranyl acetate in distilled water, phosphate buffered saline (PBS), and simulated lung fluid (SLF). These results were compared to the dissolution rate measured using the traditional filter sandwich method in which a sample is sealed between two hydrophilic membranes. Although the majority of uranyl acetate dissolved in SLF within 30 min using the filter sandwich method, most of the uranyl acetate was undissolved in PBS and SLF using the dialysis membrane device. Reactions between the dissolved uranyl acetate, solvent, and the dialysis membrane likely caused the membrane to swell, shrinking the pore size, and thus reducing the transport of dissolved uranium across the membrane. Use of the dialysis cup device for evaluating dissolution rates for uranium-bearing materials in solvents containing a high concentration of salts is therefore not recommended.     

A study of surface adsorption on silver powders

DSC and TG-DTA techniques were used to investigate micro-sized silver powder particles and the adsorption of ethyl cellulose on these particles in a solution of ethyl acetate. The apparent specific heat of the silver particles was determined, and the kinetics of temperature-programmed desorption (TPD) of these adsorbed silver particles was investigated. Results show that the apparent specific heat and desorption kinetic parameters obtained by thermal analysis techniques could be used to characterize certain physico-chemical properties of such a particulate system.     

Cellulose Derivatives Membranes as Supports for Immobilisation of Enzymes

Cellulosic derivatives (cellulose acetate, cellulose propionate and cellulose acetate-butyrate) as membranes, were prepared in different ways. These were then characterised by differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and contact angle evaluation. Subsequently, catalase (H2O2:H2O2 oxireductase; EC 1.11.1.6), alcohol oxidase (Alcohol:oxygen oxireductase; EC 1.1.3.13) and glucose oxidase (-D- Glucose:oxygen 1-oxireductase; EC 1.1.3.4) were covalently linked to these membranes. The catalytic activity and stability of these enzymes, when immobilised, were examined. The results obtained showed that the immobilisation efficiency and the stability of the coupled enzymes could be correlated with the studied properties of the supports. The cellulose acetate membrane which was prepared by evaporation gave the more active conjugate support-enzyme. Membranes prepared by the immersion technique were more crystalline and therefore less suitable for enzyme immobilisation. The highly hydrophobic membranes, obtained from the propionate and the butyrate esters of cellulose reduced the activities but gave better storage stability.     

Properties and Applications of Cellulose Acetate

Cellulose acetate is one of the most important esters of cellulose. Depending on the way it has been processed cellulose acetate can be used for great varies of applications (e.g. for films, membranes or fibers). The properties of the applied cellulose acetates are very important for these applications. A special field for using cellulose acetate is the synthesis of porous, spherical particles, so called cellulose beads. Different types of technical cellulose acetates were used and their ability to form such cellulose beads was characterized. First the different types of cellulose acetates were characterized by means of solubility; turbidity and degree of substitution. In addition the molar mass and the distribution of substituents along the polymeric chain were analyzed. Next, the cellulose beads were synthesized within an emulsion process using these different cellulose acetates. Then the properties (particle size, porosity, morphology) of the cellulose beads were determined. Finally, the relationship between the characteristic of cellulose acetates and properties of cellulose beads was investigated.     

Amphiphilic Linear-Branched Copolylactides and Disperse Systems on Their Basis

The linear-branched copolylactides containing linear side poly(ethylene oxide) blocks are synthesized and characterized. The critical micelle concentrations and the aggregative stability and the dispersity of oil/water emulsions stabilized by these copolymers are estimated. The polylactide microparticles are obtained by emulsification followed by evaporation of an organic solvent using acetylsalicylic acid as a model drug. The structure of copolylactides strongly affects the properties of the microparticles. On one hand, the presence of large poly(ethylene oxide) blocks in the linear-branched macromolecules leads to the formation of colloidal systems with a higher aggregative stability of emulsions and a lower size of particles, and on the other hand, the microparticles formed from these copolymers possess a lower incorporation efficiency relative to water-soluble low-molecular-mass compounds and the profile of the release of these compounds is nonlinear and contains the region of accelerated release.     

Effect of Bee Pollen on the Mechanical and Thermal Properties of Starch Films

The use of casein, starch and bee pollen as biodegradable materials has been promise. The objective of this work was the development and characterization of films containing casein, pollen and starch. The films were obtained by casting process and the solvent evaporation was performed at 40 °C/24 h. The films characterization was carried out by microscopy, thermal analysis, opacity test, mechanical properties and barrier methods. The starch films presented heterogeneous on microscopy analysis. The thermal behaviors of pollen films were similar. The formulation containing only pollen 3% was unable to form film. The introduction of pollen in starch film formulation improved the mechanical characteristic and thermal stability of films.     

Development of a Unifying Framework for Modeling Multi-component Diffusion in Polymer Solutions

In this work a unifying framework for modeling multi-component diffusion in mixed solvent polymer solutions is developed by introducing additional restrictions such as the Onsager reciprocal relations (ORR) and the quasi-equilibrium postulate. More specifically, three different multi-component diffusion models, namely the Zielinski and Hanley model, the Dabral et al. theory and the Alsoy–Duda model are revised by using the above restrictions which are based on sound principles of non-equilibrium thermodynamics. Realistic simulations for the solvent(s) evaporation from the water/acetone/cellulose acetate (CA) and formamide/acetone/CA systems were obtained by combining the above multi-component diffusion models with the ORR and the quasi-equilibrium postulate. It is believed that the results of this work could be used to further study diffusion in multi-component systems appearing in coating and membrane formation.