최근까지 연구가 진행되어온 bead 형태를 가진 약물수송체는 크기가 큼으로 인해서 약제 투여 방식에 큰 한계를 가지고 있다. 이를 보완하기 위해 본 연구에서는 막유화법을 이용하여 반응기의 압력과 sodium alginate의 농도 변화에 따른 alginate microparticle 약물수송체를 제조하였다. 수송체내의 약물로는 양이온성 약물인 lidocaine^.HCl, 비이온성 약물인 4-acetamidophenol, 음이온성 약물인 sodium salicylate를 사용하였으며, 이를 이온 강도 0.2의 pH 2, pH 7인 인산완충용액내에서 방출 실험을 실시하였다. 막유화법에서 alginate의 농도가 2 wt%일 때, 압력은 0.4*10⁵ Pa일 때 가장 단분산경향을 보였는데, 이는 alginate의 카르복시기와 양이온성 약물의 이온성 결합 때문이다. pH 2와 pH 7의 완충용액에서의 방출 결과는 pH 2에서 많은 지연 효과가 있는 것으로 나타났는데, 이는 카르복시기와 완충용액내의 H⁺, Na⁺에 의한 해리도의 차이 때문이다. 이로서 bead 크기의 수백분의 일인 microparticle이 민감한 pH 반응성을 보이므로 그 자체를 약물수송체로 사용할 수 있을 뿐만 아니라 여러 제약 투여 방식에 유리하게 응용될 수 있음을 알 수 있다.

Conventional alginate bead has been limited to be used as a drug carrier because of its large size. To overcome the disadvantages of conventional large-size alginate drug beads, Ca-alginate microparticles were prepared using membrane emulsification method controlled with the sodium alginate concentration and the pressure of reactor. The optimal monodispersed microparticles were obtained with the concentration of 2 wt% alginate solution and the pressure of 0.4×10⁵ Pa. The mean size of our prepared microparticles was about 4 ㎛. As the drug solutions, lidocaine·HCl(cationic), sodium salicylate(anionic) and 4-acetamidophenol(nonionic) were selected. These three different drugs were loaded in the drug carrier of prepared alginate microparticles. Drug releases were performed in the siduim phosphate buffers of pH 2 and pH 7 and ionic strength of 0.2. The release behavior with the variation of drug charge showed that of the cationic drug release was retarded more than anionic one due to the ionic interaction between carboxyl group of alginates and positive charge of cationic drug. From the comparison experiments of the buffers of pH 2 and pH 7, the release was much retarded at pH 2 buffer due to ionic repulsivw force or ionic attractive force between the carboxyl group and the hydroxy or sodium ion in the buffer. Conclusively, the usage of small-size pH sensitive microparticles as a drug carrier has a high potential for the application of drug delivery systems.

Membrane Emulsification Method Drug Carrier Alginate Drug Release

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