由於強制型製程成本高且使用溶劑，針對以微藻油和橄欖油作為藥物載體的材料，本研究透過探討製程參數對載體特性的影響，開發具規模放大潛力的均質擠壓製程。強制型製程使用的批次體積為60 mL，製備出的微藻油與橄欖油載體粒徑約為200 nm，載體界面則因游離脂肪酸存在而帶負電。在物理穩定性方面，微藻油載體可穩定長達260天以上，橄欖油載體則在製備後第25天呈現不穩定，但可透過卵磷脂的添加將橄欖油載體的穩定天數延長至194天以上。
在均質製程中，分別於60 mL、600 mL的批次體積下，探討均質參數的效應。結果顯示隨著卵磷脂添加量的提高、均質轉速上升、均質時間延長，載體粒徑有下降的趨勢。低界面張力、低黏度的微藻油比高黏度、高界面張力的橄欖油能製備出更小粒徑的載體。批次體積的放大對載體粒徑、原料利用率與物理穩定性皆有負面影響，微藻油和橄欖油600 mL分散液的載體平均粒徑皆在546 nm以上，穩定天數皆不足152天。
為了進一步減小載體粒徑，在均質製程後加入批次體積為100 mL的擠壓製程。結果顯示隨著擠壓次數的增加，載體粒徑變小、原料利用率下降、跨膜通量上升，且混合纖維酯膜比聚碳酸酯膜有更顯著的粒徑降低效果。此外，跨膜壓力的提升通常有助於油滴的破裂，然而可能因界面活性劑來不及吸附於新生界面，導致載體粒徑反而增加。跨膜壓力的提升也無法減緩油脂殘留或膜結垢程度，分散液的原料利用率皆小於40 %。針對均質擠壓製程，較佳的操作條件為—以13000 rpm均質30分鐘後，對分散液施予2 kg/cm2的壓力並使用1000 nm混合纖維酯膜擠壓三次。不論包覆葉黃素與否，經此製程製備出的載體粒徑皆小於300 nm，且除了未包覆葉黃素的橄欖油載體外，其餘載體皆具備77天以上的穩定天數。若能解決油脂殘留、膜結垢與載體穩定性不足的問題，有不使用溶劑、可規模放大、製備流程簡便等優點的均質擠壓製程會更具應用性。

The forced-formation process has drawbacks, such as high cost and use of solvent. In this study, by using microalgal oil and olive oil as the raw materials for drug carriers, the effects of process parameters on carrier characteristics were investigated in order to develop a homogenization-extrusion process with the potential of being scaled up. By a forced-formation process, a 60-mL carrier dispersion was prepared. Both of the microalgal and olive oil carriers had a size of about 200 nm, and the negatively charged characteristic of the carriers was due to the presence of free fatty acids at interfaces. For the physical stability, the microalgal oil carriers could be stable for up to 260 days, while the lifetime of the olive oil carriers was less than 25 days, which could be extended to more than 194 days with the addition of egg phosphatidylcholine.
In the homogenization process, batch volumes of 60 mL and 600 mL were adopted, respectively, to explore the process parameter effect. The results showed that as the amount of added egg phosphatidylcholine was increased, the rotation speed was raised, and the mixing time was prolonged, the carrier size seemed to be decreased. The microalgal oil with low interfacial tension and viscosity could be fabricated as the carriers with a smaller size than the olive oil with high interfacial tension and viscosity. The increase in the batch volume had negative impacts on the carrier size, usage rate, and physical stability. The average sizes of 600-mL dispersions were above 546 nm, and the lifetimes of the carriers were less than 152 days.
To further reduce the carrier size, an extrusion process with a batch volume of 100 mL was introduced after the homogenization process. As the number of extrusion pass was increased, the carrier size and usage rate were decreased, and the transmembrane flux was increased. A more significant size reduction was obtained when the mixed cellulose ester (MCE) membrane was adopted compared to the polycarbonate (PC) membrane. Furthermore, the increase in transmembrane pressure was usually useful for the rupture of oil droplets, but the carrier size might be increased probably when the surfactants could not adsorb fast enough on the newly formed interfaces. The degrees of remaining oil on membranes and membrane fouling could not be reduced by increasing the transmembrane pressure, leading to a low usage rate of less than 40 % in all cases. For the homogenization-extrusion process, the best operating condition was with homogenization at 13000 rpm for 30 min and then extrusion through 1000-nm MCE membrane under the pressure of 2 kg/cm2 for 3 times. Whether lutein was encapsulated or not, all of the carriers prepared with the process had the sizes below 300 nm and could be stable for more than 77 days, except for the case of pure olive oil carriers. If the problems of remaining oil on membranes, membrane fouling, and insufficient carrier stability could be resolved, the homogenization-extrusion process, which possessed the advantages of using no solvent, being able to be scaled up, and easy operation, would be more applicable.

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