Production of Gemcitabine-Loaded Poly (L-lactic acid) Microparticles Using Supercritical Carbon Dioxide: Effect of Process Parameters

Abstract

1) In this study, poly (L-lactic acid) (PLLA) microparticles containing gemcitabine hydrochloride were prepared by a supercritical fluid process, called aerosol solvent extraction system (ASES), utilizing supercritical carbon dioxide as antisolvent. The influence of process parameters such as temperature, pressure, CO2 and solution flow rate, solution concentration, and feed ratio of drug to polymer on the morphology and characteristics of the microparticles was studied in detail. The gemcitabine-loaded microparticles exhibited a spherical shape with a smooth surface. The entrapment efficiency of gemcitabine increased with increasing temperature, solution concentration and CO 2 flow rate and with decreasing drug/polymer feed ratio. The maximum drug loading obtained from the ASES process was found to be about 11%. The ASES-processed PLLA microparticles containing gemcitabine showed a relatively high initial burst due to the presence of surface pores on the microparticles and the poor affinity between drug and polymer.

Preparation of Gemcitabine-Loaded PLLA/Gemcitabine-PLLA Microparticles Using Supercritical Fluid and Their Release Characteristics

“…고분자 미립자 약물전달시스템에서 일반적으로 사용되고 있는 생분해성 고분자로는 poly(lactic acid) (PLA), poly(glycolic acid) (PGA), poly(lactic-co-glycolic acid) (PLGA), poly (ε-caprolactone), polyanhydride, poly(ortho ester) 등이 있다 [6]. PLA와 PLGA와 같은 polyester계 생분해성 고분자가 전 달체로써 가장 널리 사용되고 있는데, 그 이유는 생분해 속도 가 느리고, 생체 내에서 염증반응을 거의 일으키지 않는 생체 적합성이며, 대사를 통해 이산화탄소와 물로 분해되어 체외 로 배출되기 때문이다 [12]. 물리적 방법을 통해 약물이 함유된 고분자 나노 또는 미세 입자를 제조할 때 약물의 봉입효율 (encapsulation or entrapment efficiency)은 약물과 고분자간의 친화력 (affinity)에 따 라 변화하며, 저분자량의 친수성 약물이 소수성 고분자에 봉 입되는 경우 낮은 봉입효율이 나타나는 것이 일반적이다.…”