Fundamental Research On The Preparation Of Microcapsules By Supercritical Fluid Impinging Technology

Preparation technology of microcapsules plays a key role in their application. At present, the supercritical fluid technology is usually used to produce the pharmaceutical microcapsules. The representative rapid expansion of supercritical solution (RESS) and supercritical anti-solvent (SAS) methods are able to overcome the drawbacks of the traditional preparation technologies, such as large particle diameters, wide size distributions and serious agglomerations. However, RESS fails in obtaining a uniformly coating, while SAS requires that core material must deposit before wall material.Herein, we presente a new technology called supercritical fluid impinging technology (SFIT) for the preparation of microcapsule base on previous studies, which involve supercritical fluid process, impinging streams technology and fluidized-bed coating technology. SFIT overcomes the disadvantages of RESS and SAS methods for microcapsule production when taking advantage of combines RESS and fluidized-bed technology. Besides, this method also avoids the restriction of core material’s solubility in supercritical fluid, and strengthened the inter-phase mass transfer, which resultes in improving encapsulation efficiency and expanding the scope of micro-particles.According to the theory of supercritical fluid and impinging stream, we have developed an experimental facility, the corresponding experimental procedure and analysis method, and finally propose a whole set of SFIT. SFIT is investigated by using glass beads as the core material and paraffin as the wall material. The results indicate that the experimental facility satisfies the requirement of SFIT experiment completely, and the microcapsules are produced with good integrity. Furthermore, the effects of main operating parameters, such as pressure of the mixing vessel, temperature of the mixing vessel and impinging distances on the encapsulation like surface morphology, average particle size and apparent encapsulation efficiency are investigated, and thereby the optimize operating parameters are obtained.SFIT is further investigated by using pharmaceutical microcapsules. Amoxicillin as antibiotic medicine with a short half—life period and nitrendipine as hypotensive drug are chosen as the core materials, and PEG4000is chosen as the wall material. The integrity and crystal morphology of the amoxicillin/PEG4000and nitrendipine/PEG4000microcapsules obtaine by SFIT is tested with DSC and XRD. According to the requirements of the China Pharmacopoeia committee, the experimental study on drug release is also conducted to examine the coating integrity and drug releasing ability. In addition, this study dealt with the influence of different parameters such as pressure of the mixing vessel, temperature of the mixing vessel, impinging distance and pre-temperature on the morphology, particle size and size distribution, and drug loading capacity. The optimized operating parameters are thereby obtained.SFIT is also investigated using another pharmaceutical microcapsule. Vitamin C which is fast releasing, chemically unstable and easy to degrade is selected as the core material, and PLLA which is biodegradable and popular in pharmaceutical field is selected as the wall material. The Vc/PLLA microcapsule obtains by SFIT is valuated with XRD. The sustained-release experiment is conducted using a buffer solution, and the corresponding drug release rate is obtained by UV-visible spectrophotometer. In addition, the effects of different parameters such as pressure of the mixing vessel, temperature of the mixing vessel, impinging distance and pre-temperature on the characteristics such as the morphology, particle size and size distribution, and drug loading capacity of microcapsules are investigated, and thereby the optimized operating parameters for VC/PLLA microcapsule producing process are obtained.The flow field in SFIT process is studied with PIV. The area from the jet outlet to the impinging surface is selected to be the research zone.The effects of operating parameters such as pressure of the mixing vessel, temperature in the mixing vessel and impinging distance on the axial velocity are studied. Thus, the velocity vector diagram and the regular pattern how the parameters affect the flow fields are obtained.