Layered lipid microcapsules for mesalazine delayed-release in children

The goal was to make available a delayed-release dosage form of mesalazine to be dispersed in water to facilitate swallowing in adults and children. Mesalazine microparticles containing carnauba wax were prepared by spray-congealing technique. A second step of spray-congealing of carnauba microparticles dispersed in liquefied stearic acid gave rise to mesalazine lipid microcapsules in which several carnauba microparticles remained embedded as cores in a reservoir structure. In order to favor their water dispersion, the lipid microcapsules were dry coated by tumbling them with different ratios of mannitol/lecithin microparticles prepared by spray-drying. Release rate measurements showed a delayed-release behavior, in particular a pH-dependence with less than 10% of drug released in acidic medium and complete release in phosphate buffer pH 7.4 in 4-5h. The layering with hydrophilic excipient microparticles allowed manufacturing of a pH-dependent dosage form suitable for extemporaneous oral use in adults and children.     

Dye diffusion from microcapsules with different shell thickness into mammalian skin

Oil-in-water microcapsules with varying shell thicknesses were fabricated via a coacervation technique, whereby evaporation of volatile solvents induced the shell-forming polymer to precipitate, phase separate and migrate to the oil/water interface to form microcapsules. These microcapsules encapsulated a lipophilic dye within their cores and were applied topically onto porcine skin for 6 h. Results indicated that the dye preferentially accumulated within the skin furrows and hair follicles, though the dye did not penetrate beyond the stratum corneum. A model estimates the diffusion coefficients of dye through the microcapsule shell and within the skin to be approximately 10⁻¹⁸ and 10⁻¹⁶ m² s⁻¹, respectively.     

微囊豚鼠肝细胞培养及其细胞免疫屏障作用的观察

目的 观察海藻酸钠-多聚赖氨酸-海藻酸钠(APA)微囊化肝细胞的生物学功能及对免疫细胞的隔离效应。方法 用胶原酶门腔静脉灌注法分离豚鼠肝细胞,测定微囊化肝细胞及游离肝细胞培养上清白蛋白水平,用自然杀伤细胞(NK)细胞的细胞毒实验来评价微囊的免疫隔离效应。结果 微囊包裹对肝细胞的活率无明显影响,微囊化肝细胞与裸露肝细胞白蛋白分泌水平差异无显著性(P>0.05),NK细胞对K562靶细胞的细胞毒实验表明微囊可有效地保护囊内细胞不受NK细胞的杀伤作用。结论 APA微囊化肝细胞可保持良好的生物活性,APA微囊对细胞免疫具有免疫隔离作用。     

Controlled release of vancomycin from biodegradable microcapsules

Poly D,L-lactic acid (PLA) and its copolymers with glycolide PLGA 90:10 and 70:30 were polymerized under various conditions to yield polymers in the molecular weight range 12000-40000 daltons, as determined by gel permeation chromatography. Vancomycin hydrochloride was the hydrophilic drug of choice for the treatment of methicillin resistant Staphyloccoccal infections. It was microencapsulated in the synthesized polymers using water-oil-water (w/o/w) double emulsion and solvent evaporation. The influence of microcapsule preparation medium on product properties was investigated. An increase in polymer-to-drug ratio from 1:1 to 3:1 caused an increase in the encapsulation efficiency (i.e. from 44-97% with PLGA). An increase in the emulsifier (PVA) molecular weight from 14-72 kD caused an increase in encapsulation efficiency and microcapsule size. The in vitro release of vancomycin from microcapsules in phosphate buffer saline (pH 7.4) was found to be dependent on molecular weight and copolymer type. The kinetic behaviour was controlled by both diffusion and degradation. Sterilization with ⁶⁰Co (2.5 Mrad) also affected the degradation rate and release profiles. Degradation of microcapsules could be seen by scanning electron microscopy, by the increase in the release rate from PLA and by the decrease in the T_g values of microcapsules. In vitro bactericidal effects of the microcapsule formulations on S.aureus were determined with a special diffusion cell after the preparations had been sterilized, and were found to have bactericidal effects lasting for 4 days.     

Tableting of coated ketoprofen pellets

Ketoprofen pellets were prepared by the method of extrusion-spheronization, and a film coating of guar gum and Eudragit NE was applied to drug cores using pan technology. In an attempt to design a tablet which, on peroral administration, disintegrates rapidly, releasing intact coated pellets which maintain the integrity of both the cores and their release retarding membrane, Avicel PH101, lactose DT and magnesium stearate were used as excipients to prepare tablets comprising ketoprofen pellets or microcapsules. Preliminary experiments were conducted on uncoated pellets to determine the optimum compression force required to prepare tablets of satisfactory mechanical properties and release profiles. Coated pellets containing ketoprofen were used to investigate the influence of excipients levels. In an attempt to minimize problems associated with blending and segregation of microcapsules and excipients, placebo spheres of Avicel PH101 and lactose DT were produced by the method of extrusionspheronization. The use of placebo spheres produced tablets with improved drug content uniformity and disintegration time. The tensile strength of such compacts was enhanced by excluding magnesium stearate from the mixes without significant problems of sticking or picking. The use of placebo pellets resulted in significant damage to drug microcapsules, which was attributed to the higher hardness and density of the excipients pellets. The role of membrane coating in protecting the drug core during compression was also evaluated.     

Preparation and stability of agarose microcapsules containing BCG

An emulsification/internal gelation method of preparing small-sized agarose microcapsules containing Bacillus Calmette-Guérin (BCG) is reported. Agarose microcapsules have been prepared by the emulsification of the hydrogel within a vegetable oil followed by its gelation due to the cooling of the system. Four different oils (sesame, sweet almonds, camomile and jojoba) were assayed. The rheological analysis of the oils showed a Newtonian behaviour, with viscosity values of 37.7, 51.2, 59.3 and 67.1 mPa s for jojoba, camomile, sesame and sweet almonds oil, respectively. The particle size of the microcapsules obtained ranged from 23.1 #181;m for the microcapsules prepared with sweet almonds oil to 42.6 #181;m for those prepared with jojoba. The microcapsule particle size was found to be dependent on the viscosity of the oil used in the emulsification step. The encapsulated BCG was identified by the Difco TB stain set K, followed by observation under optical microscopy. Once prepared, microcapsules were freeze-dried using 5% trehalose as cryoprotectant and the stability of the microcapsules was assayed during 12 months storage at room temperature, observing that agarose microcapsules were stable after 12 months storage, since there was no evidence of alteration in the freeze-dried appearance, resuspension rate, observation under microscope, or particle size.     

Mechanical properties of melamine-formaldehyde microcapsules

Abstract

The entrapment of loperamide hydrochloride (LPM) in biodegradable polymeric drug carriers such as nanoparticles might enable its passage across the blood-brain barrier. The optimization of the preparation of the LPM-loaded PLA nanoparticles was performed employing high pressure emulsification-solvent evaporation., The resulting nanoparticles were characterized by particle sizedistributionthermal analysisand drug release profiles., The partition of LPM into the organic phase increased with an increase in pH of the aqueous phase and with addition of lipophilic surfactants such as sorbitan fatty acid estersresulting in an increase in the drug entrapment in the nanoparticles., Evaporation of the organic phase under reduced pressure and the addition of ethanol in the organic phase yielded a high drug entrapment due to the rapid polymer precipitation., The addition of the sorbitan fatty acid esters further increased the drug entrapment even at higher LPM concentrations., The results of thermal analysis suggest that LPM was homogeneously dispersed in the amorphous polymer matrix., The in vitro release of the drug from nanoparticles was biphasicwith a fast initial phasefollowed by a second slower phase., Different drug release profiles from nanoparticles can be achieved by addition of sorbitan fatty acid estersor the employment of different solvents as the organic phase.     

Microencapsulation of thyme oil by coacervation

The objective of this work is to develop a novel coacervation process to produce microcapsules of polylactide (PLA) to encapsulate thyme oil that will be used in cosmetics. The novelty of this approach consists of dissolving PLA in dimethylformamide (DMF) which is a good solvent for PLA but in addition has high solubility in water. Upon contact with water, the homogeneous solution of PLA in DMF promotes the precipitation of PLA around the thyme oil core. The produced microcapsules have bimodal particle size distributions in volume with a mean particle size of 40 µm. Microcapsules analysis by microscopy have confirmed the spherical shape, the rough surface and allowed the estimation of the wall thickness around 5 µm. Quantification of the encapsulated thyme oil was performed by gas chromatography and allowed to evaluate the quality of the encapsulated oil and pointed out for a preferential encapsulation of thyme oil apolar compounds.     

Preparation of microcapsules and control of their morphology

For the preparation of microcapsules using the W/O/W (water in oil in water) emulsion system, it is essential to control various factors such as the dispersed state of the organic phase in the W/O/W emulsion, the difference in the solute concentration between the inner and outer aqueous phases and the volume fraction of the dispersed phase. In this study, cross-linked microcapsules were prepared by the in-situ polymerization of styrene and divinylbenzene and biodegradable microcapsules were prepared by the solvent evaporation method. The effects of the preparation conditions on the capsule morphology and entrapment efficiency of water-soluble materials were investigated. The average diameter of the surface pores and internal hollows were controlled on a sub-micron order by changing the preparation conditions such as diluent concentration, volume fraction of the dispersed droplets in the W/O (water in oil) emulsion, surfactant concentration monomer ratio and salt concentration in the outer aqueous phase. Furthermore, the water-soluble materials were completely entrapped in the biodegradable microcapsule by changing the preparation conditions such as volume fraction of the dispersed droplets in the W/O emulsion, salt concentration in the inner and outer aqueous phases, polymer concentration and supersonic irradiation of the W/O droplets.     

Influence of synthesis parameters on properties and characteristics of poly (urea-formaldehyde) microcapsules for self-healing applications

Abstract

Poly(urea-formaldehyde) (PUF) microcapsules filled with dicyclopentadiene (DCPD) were prepared by in situ polymerisation and the effect of synthesis parameters, such as pH of the solution and agitation rate, on microcapsules size and shell thickness was evaluated. Scanning electron microscopy (SEM) and Fourier transform infra-red spectroscopy (FTIR) were performed. Adjusted pH conditions (pH = 3.5) and agitation rate (1350?RPM) were found using a design of experiments (DOE). SEM results indicated that microcapsule size was directly affected by agitation rate, whereas shell thickness was mostly affected by pH. After obtaining adjusted synthesis conditions, microcapsules presenting mean size of 60?µm and mean shell thickness of 4?µm were embedded in an epoxy matrix for evaluating the self-healing effect. FTIR and SEM analyses in damaged samples suggested that a healing agent was delivered to the crack location.