Poly(ethylene oxide)/poly(ε-caprolactone) 혼합 매트릭스로부터 Pseudo Zeroth Order Kinetic에 의한 약물 방출 조절

유영태; 정채열

Polymer(Korea), Vol.18, No.1, 103-112, January, 1994

Export Citation

Poly(ethylene oxide)/poly(ε-caprolactone) 혼합 매트릭스로부터 Pseudo Zeroth Order Kinetic에 의한 약물 방출 조절

Controlled Drug Release from Poly(ethylene oxide)/poly(ε-caprolactone) Blends via Pseudo-Zeroth Order Kinetics

유영태, 정채열

초록

생분해성 지방족 폴리에스터인 poly(ε-caprolactone)(PCL)과 친수성 고분자인 poly(ethylene oxide)(PEO)의 혼합 매트릭스에서 PEO의 함량, 필름두께 및 모폴로지에 따른 모델 약물인 p-nitroaniline(p-NA)의 방출거동을 조사하였다. PCL고부터 p-NA의 방출거동은 비례 누적 방출량(%Q)이 시간의 제곱근에 비례하는데 비해 PEO와 상용화제(PEO-b-PCL)를 혼합할 경우 20wt% PEO에서 시간의 0.72-0.80승에, 30wt%에서는 0.78∼0.82승에, 40wt%에서는 0.82∼0.85승에, 50wt%에서는 0.91∼0.94승에 비례하여 점차 zeroth-order kinetics로 접근하는 경향을 보였다. 이와같은 현상은 블렌드에서 PEO의 선택적인 침출로 다공성 구조를 형성하여 고/액 경계면이 지속적으로 증가하는데 기인한 것으로 전기회로 개념을 도입하여 설정한 총괄 방출속도모델을 유도하여 해석 하였다.

Release characteristics of model drug(p-nitroaniline) (p-NA) from poly(ethylene oxide)(PEO)/biodegradable poly(ε-caprolactone) (PCL) blends matrix was studied with respect to composition, thickness and morphology of the film. Fractional cumulative release(% Q) of the drug showed a linear relationship with (release time)^0.5 for PCL matrix, whereas the exponent increased to 0.72∼0.80, 0.78∼0.82, 0.82∼0.85, 0.91∼0.94 on PEO(20)/PCL(80)/PEO-b-PCL(2), PEO(30)/PCL(70)/PEO-b-PCL(3) PEO(40)/PCL(60)/PEO-b-PCL(4) and PEO(50)/PCL(50) /PEO-b-PCL(5) blends, respectively, approaching a zeroth order kinetic. This fact may be attributed to the selective dissolution of PEO from the matrix, resulting in a porous structure with expanded solid/liquid interface. The system was analyzed by a drug release model derived by an analogy of an electric circuit.

[References]

Bailey WJ, Tirrell DA, "Macromolecules as Drug and as Carriers for Biologically Active Materals," pp. 42-49, The N.Y. Academy of Science, N.Y. (1985)
Rhine WD, Hsieh DST, Langer R, J. Pharm. Sci., 69, 265 (1980)
Langer R, Brem H, Tapper D, J. Biomed. Mater. Res., 15, 267 (1981)
Heller J, Biomaterials, 1, 1 (1980)
Heller J, J. Polym. Sci. C: Polym. Lett., 18, 617 (1980)
Benedict CV, J. Appl. Polym. Sci., 28, 327 (1983)
Huang S, Mark H, "Encyclopedia of Polymer Science and Technology," Vol. 2, pp. 237-257, Wiley-Interscience, New York (1989)
Tabushi I, J. Polym. Sci. C: Polym. Lett., 13, 447 (1975)
Greham NN, Br. Polym. J., 10, 260 (1978)
Vergnaud JM, "Liquid Transport Process in Polymeric Materials, pp. 221-353, Prentice Hall, Inc., Englewood Cliffs, New Jersey (1991)
Liversidge G, Nair M, Tan J, Research Proposal on "Parentral Polymeric Nanoparticulate Drug Delivery," Presented to the Sterling Drug Company, March 17 (1988)

[Referenced By]

[1] Bailey WJ, Tirrell DA, "Macromolecules as Drug and as Carriers for Biologically Active Materals," pp. 42-49, The N.Y. Academy of Science, N.Y. (1985)

[2] Rhine WD, Hsieh DST, Langer R, J. Pharm. Sci., 69, 265 (1980)

[3] Langer R, Brem H, Tapper D, J. Biomed. Mater. Res., 15, 267 (1981)

[4] Heller J, Biomaterials, 1, 1 (1980)

[5] Heller J, J. Polym. Sci. C: Polym. Lett., 18, 617 (1980)

[6] Benedict CV, J. Appl. Polym. Sci., 28, 327 (1983)

[7] Huang S, Mark H, "Encyclopedia of Polymer Science and Technology," Vol. 2, pp. 237-257, Wiley-Interscience, New York (1989)

[8] Tabushi I, J. Polym. Sci. C: Polym. Lett., 13, 447 (1975)

[9] Greham NN, Br. Polym. J., 10, 260 (1978)

[10] Vergnaud JM, "Liquid Transport Process in Polymeric Materials, pp. 221-353, Prentice Hall, Inc., Englewood Cliffs, New Jersey (1991)

[11] Liversidge G, Nair M, Tan J, Research Proposal on "Parentral Polymeric Nanoparticulate Drug Delivery," Presented to the Sterling Drug Company, March 17 (1988)