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Introduction of Methyl Propionate to Oil-in-Water Emulsion Based Microencapsulation

Title
Introduction of Methyl Propionate to Oil-in-Water Emulsion Based Microencapsulation
Authors
강주경
Issue Date
2014
Department/Major
대학원 생명·약학부약학전공
Publisher
이화여자대학교 대학원
Degree
Master
Advisors
사홍기
Abstract
The purpose of this study was to apply methyl propionate as a non-halogenated dispersed solvent for oil-in-water emulsion based poly-d,l-lactide-co-glycolide(PLGA) microencapsulation technique for the first time. Several methods were used for that purpose. A solvent evaporation-extraction hybrid encapsulation technique was developed, and progesterone was chosen as a model drug for microencapsulation. All experiments were conducted in comparison with an ethyl acetate-based microencapsulation process to evaluate applicability of methyl propionate. It was found that methyl propionate was shown to have less water miscibility and greater evaporative tendency than those of ethyl acetate. The results indicated that methyl propionate could not only provide microspheres better quality but also offer an advantage in the process of solvent removal. Microspheres prepared by methyl propionate based microencapsulation had the average volume mean diameter of 68.3 ± 1.6 ㎛ and span index value of 0.91 ± 0.13. Polymorphic transition of the model drug did not occur during microencapsulation process. Also, drug encapsulation efficiency was determined to be from 41.80 ± 1.83% to 85.64 ± 1.95%. Residual solvent in microspheres was from 0.97 ± 0.03% to 1.54 ±0.07%. These results were comparable to those prepared by the ethyl acetate based microencapsulation. In summary, methyl acetate was found to be an invaluable dispersed solvent for an emulsion-based microencapsulation process. Since methyl propionate had several advantages over ethyl acetate, the former might find versatile applications in the preparation of various microspheres. ;본 연구의 목적은 비할로겐 용매로서 methyl propionate를 처음으로 o/w 유제를 기반으로 한 microencapsulation에 도입하는 것이다. 기존에 제약 공정에서 주로 사용되고 있는 ethyl acetate를 이용하여 제조한 미립자와의 비교를 통하여 methyl propionate가 microencapsulation 분야에서 사용될 수 있는 잠재력과 가능성을 제시하는 것이다. 본 실험을 위하여 methyl propionate를 사용한 유제 기반의 microencapsulation 기법을 고안하였으며 생체 내에서 분해되는 poly-d,l-lactide-co-glycolide(PLGA)와 progesterone을 모델 약물로 microspheres 제조를 위해 사용하였다. 용매의 물성과 제조한 microspheres의 특성은 ethyl acetate를 기반으로 제조한 microspheres의 특성과 비교하였다. 본 실험의 결과로 methyl propionate는 ethyl acetate보다 더 큰 증발 양상을 보여주며 물과의 혼화도가 낮다는 것을 알 수 있었다. 이러한 특징은 microencapsulation 과정에서 품질이 우수한 microspheres를 제조할 수 있다는 장점으로 작용한다. 또한, Methyl propionate를 사용하여 제조한 microspheres의 체적 평균 입자경은 68.3 ± 1.6 ㎛ 로 0.91 ± 0.13의 span index 값을 가졌다. 모델 약물인 progesterone은 microencapsulation 과정에서 다형 전이가 일어나지 않고, 약물의 봉입율은 초기에 넣어주는 약물의 양에 따라 41.80 ± 1.83%에서 85.64 ± 1.95%의 범위로 나타났다. Microspheres 내부의 잔류 용매는 0.97 ± 0.03%에서 1.54 ± 0.07% 범위의 양으로 나타났다. Methyl propionate를 분산상으로 사용하여 제조한 microspheres의 특성은 ethyl acetate를 사용하여 제조한 microspheres의 성질과 매우 유사하게 나타났다. 본 실험에서 새롭게 제시한 분산상으로서의 methyl propionate는 microencapsulation 분야에서 다양하게 응용될 수 있을 것이다.
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