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Propranolol, HC1-ion-exchange albumin microcapsules의 방출 특성에 관한 연구

Title
Propranolol, HC1-ion-exchange albumin microcapsules의 방출 특성에 관한 연구
Other Titles
Release charcteristics on PropranololㆍHCI-ion-exchange albumin microcapsules
Authors
박신아
Issue Date
1991
Department/Major
대학원 약학과
Keywords
PropranololHC1albumin microcapsules방출 특성
Publisher
이화여자대학교 대학원
Degree
Master
Advisors
구영순
Abstract
Empty cross-linked albumin microcapsules were prepared by chemical denaturation method using cross-linking agent. The binding efficiency of cross-linked albumin microcapsules was evaluated as a function of various conditions. Increasing the extent of cross-linkage of the empty albumin microcapsules walls by increasing either the cross-linking agent concentration or the tile of stirring significantly reduced the binding ability of these microcapsules. Increasing the amount of the microcapsules or decreasing the mean particle diameter of the microcapsules increased the binding rate and total amount of propranolol bound, as expected. The lower the initial propranolol concentration, the higher the extent of binding ability of these microcapsules. Propranolol release characteristics revealed that the presence of a salt in the release medium was needed to enable much of the drug to be released or the presence of electrolytes in this aqueous solution profoundly altered the release profile of propranolol. Increasing the NaCl concentration in the solution increased the total amount of drug released. Furthermore, the propranolol displacement intensity from the microcapsules was dependent on the nature, concentration, ionic strength of the cations used, indicating that an ion-exchange process was involved. These results suggested that there is a competitive fixation of the cation on the binding sites(identified as RCOO^(-)) available to the drug molecules. The release rates of propranolol. HC1 from the propranolol·HCl-ion -exchange albumin microcapsules retarded considerably compared with propranolol·HCl powder; release of propranolol·HCl powder was completed within 1 minute, but release of propranolol·HCl from propranolol-ion-exchange albumin microcapsules, designed to BSA:GA 1:0.025(w/w), was 25% within 1 minute. SEM showed that microcapsules were almost spherical but prepared with a terephthalnyl chloride as a cross-linking agent presented rippled surfaces. In conclusion, the cross-linked albumin microcapsules acted as cation-exchange resins which can exchange their labile electrolytes with the protonated drug present in the solution.;Albumin microcapsules을 제조하는 데는 heat denaturation법과 chemical denaturation법 등이 있는데 본 실험에서는 chemical denaturation법으로 cross-linking agent의 종류 (glutaraldehyde, terephthaloyl chloride), 농도 및 교반시간을 달리하여 interfacial polymerization으로 empty albumin microcapsules(이하 E-MC)을 제조하여 ion-exchange method로 E- MC에 약물을 incorporation 시키고 약물의 방출특성을 관찰하였다. Positive charge를 띠는 Propranolol·HCl(이하PPH)을 Model drug으로 선택하고 방출의 조절 및 지속성를 검토하였다. Cross-linking agent로 GA를 사용하였을 경우 E-MC에 incorporation된 약물양은 TP를 사용한 경우의 3배 이상이었다. GA 농도를 낮게, 교반시간을 짧게 하여 제조한 E-MC에는 약물양이 많이 incorporation되었다. E-MC의 양이 많을수록, E-MC의 Particle size가 작을수록, incorporation되는 약물양은 많았다. 0.9% NaCl 수용액에서 약물 원말이 1분 이내에 99% 이상이 용해되는데 비해 ion-exchange albumin microcapsules로부터의 약물방출은 25%로 4배 이상 지연되었다. Nacl 농도가 높아지거나 방출 교반속도가 빠르면 방출되는 약물양이 많아지며 NaCl에 비해 이온강도가 큰 CaCl_(2), MgCl_(2)를 같은 농도로 하여 사용한 경우 방출되는 약물양을 1분에 NaCl의 경우의 1.5배였다. 제조된 E-MC를 SEM으로 관찰하여 본 결과 crossing-linking agent로 GA를 사용한 것은 구형이었고 TP를 사용한 것은 쭈글쭈글한 형태였으며 약물을 incorporation한 albumin microcapsules 및 방출 완료 후의 albumin microcapsules의 외관은 차이가 없었다.
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