Air-filled polymeric microcapsules from emulsions containing different organic phases.

Air-filled polymeric microcapsules for use as a contrast agent in ultrasonography have been prepared by the freeze-drying of different oil-in-water emulsions. The water phases consisted of a block copolymer in water. The organic phases consisted of a biodegradable polyester dissolved in (-)-camphene, cyclooctane, cyclohexane or tricyclene, which were relatively poor solvents for the polyester. A polymeric wall was, therefore, precipitated at the droplet surface early in the process, i.e. during freezing. Removing the solvent during freeze-drying, resulted in air-filled microcapsules. The microcapsules were suspended in saline after freeze-drying. All the suspensions contained echogenic microcapsules with a volume mean diameter of approximately 5-7 microm. Microscopic investigations showed that the microcapsules were spherical and hollow. Tricyclene and, to some degree, (-)-camphene were found unsuitable for industrial production due to melting points above 30 degrees C. Cyclooctane and cyclohexane were investigated as replacements for the initially chosen (-)-camphene, since they are liquids over a wider temperature range. These solvents gave improved yields, measured both as particle volume concentration per amount of polymer in suspension and acoustic attenuation at 3.5 MHz per amount of polymer in suspension, although the freeze-drying cycle was not optimized for these systems.

Preparation of polymeric microcapsules: formulation studies.

Air-filled microcapsules were prepared by freeze-drying different oil-in-water emulsions containing biodegradable polyester as the wall-forming material. The aim of this work was to find an acceptable formulation with respect to the microcapsule suspension and the stability of the emulsion during the production process. The influence of various formulation parameters (concentrations of mannitol, polymer, and surfactant; pH; oil-in-water phase ratio) was investigated in a factorial design. The results were treated by ordinary least-square (OLS) regression and partial least-square regression (PLSR). In a previous work, air-filled microcapsules were successfully made using human serum albumin as the surfactant in the emulsion (1). In the present work, a new block copolymer based on poly(ethylene glycol) (PEG) was implemented as the surfactant to replace human serum albumin. It was found that the new block copolymer is a suitable replacement for human serum albumin. The concentration of the polymer in water and the concentration of the surfactant in the oil phase and the interaction between these variables had a significant influence on the stability of the emulsion at 60 degrees C. A surfactant concentration of approximately 2% (w/v) in water was necessary when the concentration of the wall-forming polymer was below 5% (w/v) in (-)-camphene. The concentration of the polymer in the oil phase influenced the yield, measured as the volume concentration of particles in suspension per milligram of polymer added and as acoustic effect per milligram of polymer. Low levels of polymer concentration in (-)-camphene (< 5% w/v) gave the highest yield. Excess polymer in the oil phase did not form microcapsules, but precipitated in the suspension or was included in the wall of the microcapsules. Addition of mannitol protected the microcapsules from being destroyed during freeze-drying and resulted in freeze-dried products with few cracks, little shrinkage, and higher suspension yield.

Characterization of enteric-coated tablets and pellets by two in vitro dissolution methods and by scanning electron microscopy.

The in vitro dissolution rates of enteric-coated pellets and tablets containing dexchlorpheniramine maleate (DCPM) were obtained using the USP XXI paddle and a flow-through method. Pellets were produced by extrusion and spheronization. Tablets were produced by direct compaction, and by wet granulation. The products were coated with different amounts of Eudragit L30D using fluid-bed technology. Onset of release, determined by fitting of the Weibull function, was the only factor found to be affected by the amount of coating of the tablets. For pellets, both onset of release and dissolution rate showed significant differences. Scanning electron microscopy was used to study the effect of different dissolution media on the coating. Acidic medium was found to alter the coating surface, but the coating did not rupture during the time used in this study.