| dc.description.abstract | The double-encapsulated microcapsules were prepared by the non-solvent addition phase-separation method to form the first encapsulated microcapsule and, then, were encapsulated again using the O/W emulsion non-solvent addition method to mitigate drug loss and achieve zero-order sustained-release. The O/W emulsion solvent evaporation method was also used to prepare the microcapsules for mitigating drug loss and achieve zero-order sustained-release. Theophylline and ethylcellulose were used as the core material and shell material, respectively. The effects of the total TH/EC ratios of the double-encapsulation emulsion non-solvent addition method on particle size, surface morphology, drug loss, release rate and release behavior of microcapsules were investigated.
The particle size of microcapsules was affected by the viscosity of the polymer solution, the rate of phase-separation and the interface-tension between the polymer solution droplet and water phase. In the double-encapsulated process, the particle size of the microcapsules was the smallest when the total EC/TH ratio was 1.0. This was due to the high viscosity of the polymer solution causing the polymer chain to precipitate too quickly. In the O/W emulsion solvent evaporated process, because the interface-tension between the polymer solution droplet and water phase was reduced so that the particle size of microcapsules was small by adding the polar co-solvent. When the added amount of polar co-solvent was over a specific level, the viscosity of the polymer solution could be increased to cause a large particle size. The particle size of the microcapsules could be reduced when an amount of alkane co-solvent added to the polymer solution was decreased.
The drug loss could be mitigated whenever microcapsules were prepared by the double-encapsulation method or O/W emulsion solvent evaporation method. The drug loss could be especially mitigated by about 20% when the microcapsules were prepared by adding an alkane co-solvent during the O/W emulsion solvent evaporated process. The range of the drug-release rate of the double-encapsulated microcapsules was broad due to the change in the thickness and construction of the double EC film. When the microcapsules were prepared by the O/W emulsion solvent evaporation method, the factors affecting the drug-release rate of the microcapsules were : 1. the time the microcapsules hardened in the water phase, 2. the extent to which the polymer chain stretched, 3. the amount of non-solvent remaining. The range of the drug-release rate of the microcapsules was also influenced by these three factors. The range of T20 could be drastically extended from 2.7 — 7.7 hours that of single-encapsulated microcapsules to 2 — 35.4 hours. In the O/W emulsion solvent evaporation process, the T20 of the microcapsules prepared by adding a co-solvent could be extended from 4 hours to 71.3 hours. Thus, the range of the drug-release rate was broader than the others.
As for dissolution kinetics, the double-encapsulated microcapsules could fit a zero-order release model due to its nonuniform drug distribution dosage form. At least the first 30% of the drug released fit a zero-order release model whenever any kind of alcohol co-solvent was added to prepare the microcapsules. The release behavior of the microcapsules prepared by adding n-hexane and n-heptane in the O/W emulsion solvent evaporated process was closer to zero-order than that of the microcapsules prepared by adding n-octane, n-nonane and n-decane. This was because the boiling points of n-hexane and n-heptane are lower than those of the other three alkane co-solvents resulting in their microcapsules possessing a more porous structure. When the added amount of n-octane, n-nonane and n-decane was 25%, more co-solvent remained so that when the remained co-solvent was removed by after treatment, the porosity increased, and, therefore, the resistance to the drug release was decreased. This resulted in their released behavior fitting more closely to a zero-order released model. | en_US |