| 摘要: | 微囊包覆技術已廣泛用於製藥、食品、生物技術等領域。本實驗主要設計海藻酸鈉晶球（Alginate beads），包覆親水性藥物-孟加拉玫瑰紅（Rose Bengal；RB）與疏水性藥物-葉黃素/玉米黃質（Lutein/zeaxanthin），利用反應曲面法探討自變數（羧甲基纖維素鈉（Carboxymethyl cellulose；CMCH））濃度、交聯時間、氯化鈣濃度）對於反應變數（包覆率、粒徑、最大壓破力、延展性）之影響性。
根據研究顯示，RB晶球的包覆率受到交聯時間、CMCH濃度、氯化鈣濃度所影響；CMCH添加則能使RB晶球粒逐漸變大；RB晶球的最大壓破力與延展性則受到CMCH、氯化鈣與交聯時間所影響。另一方面，包覆Lutein/zeaxanthin於反應曲面法顯示包覆率不受自變數所影響，含量皆於100%；粒徑、延展性與最大壓破力則與氯化鈣濃度以及CMCH具有高度相關性。
依照反應曲面法之所獲得的最適處方結果進行藥物包覆率，但發現RB包覆率未達理想要求（僅67%），所以處方中嘗試添加其他高分子聚合物（明膠、PVP K40）或其他製備方式（梯度法、alginate capsule）改善RB晶球包覆率之缺失。結果顯示處方中添加明膠（0.5%）即可將RB含量上升至98%，且質地與形狀與未添加明膠之晶球相似；添加PVP K40或梯度法、alginate capsule製備方式，雖可提升RB包覆率，但質地較堅硬，不利壓碎塗抹。此外，晶球安定性為期一個月試驗結果得知晶球能避免RB因受光照而產生光漂白現象；Lutein/zeaxanthin晶球之安定性則受溫度影響，於實驗結果顯示室溫保存一個月後最多約剩50%，四度保存一個月後則剩70%左右。
總結研究得知，海藻酸鈉晶球可以藉由調整高分子聚合物比例、氯化鈣濃度、交聯時間來獲得具有局部塗抹之晶球。此外，也發現高分子聚合物濃度似乎在調整包覆率、粒徑、硬度都具有影響性。
Microcapsulation has been widely used in pharmaceutical, food, and biotechnology. In this study, we focused on design alginate bead formulations, encapsulating hydrophilic drugs - Rose Bengal（RB）and hydrophobic drugs –lutein/zeaxanthin. The effects of sodium alginate to polymer ratio, CaCl2 concentration and crosslinking time on the encapsulation efficiency, particle size, hardness, and spreadability of the beads were optimized by using response surface methodology（RSM）.
Our results showed the encapsulation efficiency of RB was significantly affected by the concentration of carboxymethyl cellulose （CMCH）, CaCl2 concentration as well as the crosslinking time. Size of the beads containing RB increased by increasing the content of CMCH. The hardness and spreadability of the beads increased by increasing the concentration of CMCH, CaCl2 and cross-linking time. On the other hand, the encapsulation efficiency, particle size, hardness and spreadability of alginate beads containing hydrophobic drug were strongly affected by the concentration of CMCH and CaCl2.
In addition, the low encapsulation efficiency of alginate beads containing RB was found. Thus, adding gelatin, PVP K40, and different preparation methods（gradient method、alginate capsule）were selected to improve its encapsulation efficiency. The results showed that adding gelatin（0.5%）to the formulation could increase the encapsulation efficiency from 67% to 98% without changing the texture and shape of the beads. Adding PVP K40 or modifying the preparation methods was found to enhance the encapsulation efficiency, but the beads became harder and were not easy to smear. Stability test of alginate beads showed that the beads can prevent photobleaching of RB from light, and the degradation rate of Lutein/zeaxanthin greatly affected by the temperature.
In conclusion, the formulation optimization of alginate beads using as topical drug delivery system can be obtained by adjusting sodium alginate to polymer ratio, CaCl2 concentration and crosslinking time. Moreover, sodium alginate to polymer ratio seems to play the most important role regarding size, encapsulation efficiency and hardness and spreadability of the alginate beads forming. |
