Korean Chemical Engineering Research

The Korean Institute of Chemical Engineers (한국화학공학회)
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Optimization of Process Variables for Grinding of Ibuprofen using Response Surface Methodology

반응표면분석법을 이용한 이부프로펜의 분쇄공정변수의 최적화

  • Sim, Chol-Ho (Department of Fine Chemistry and Advanced Materials, Sangji University)
  • 심철호 (상지대학교 정밀화학신소재학과)
  • Received : 2013.05.14
  • Accepted : 2013.07.07
  • Published : 2013.12.01
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Abstract

Ibuprofen, non-steroidal anti-inflammatory drugs; NSAIDs, is a highly crystalline substance with the pharmaceutical properties of poor solubility and low bioavailability. The size reduction of ibuprofen is needed to improve the solubility. The objective of this study is to optimize the grinding condition of ibuprofen. Grinding of ibuprofen was carried out using a planetary mill. Grinding parameters were optimized using Box-Behnken experimental design method. The physical characteristics of ground ibuprofen were investigated for the particle size by particle size analyzer, for the crystal size by X-ray diffraction (XRD), and for the tensile strength by tensile/compression tester. The optimum conditions for the milling of ibuprofen were 290 rpm of the revolution number of mill, 24.6 g of the weight of sample, and 10 minutes of grinding time. The measured value of the particle size of ground ibuprofen at these optimum conditions was $13.5{\mu}m$. The results showed that the crystal size of ibuprofen was reduced by the planetary milling process. In case the relative density of the tablets formulated of ground ibuprofen was range of 0.85~0.90, the tensile strength of them was range of 1$2{\sim}14Kg_f/cm^2$.

이부프로펜은 비스테로이드성 소염진통제(Non-Steroidal Anti-Inflammatory Drugs; NSAIDs)의 대표적인 성분이다. 이부프로펜은 결정성이 크기 때문에 난용성이며, 따라서 생체이용률(bioavailability)도 낮다. 이와 같은 난용성을 개선하기 위해서는 이부프로펜의 입도를 감소시킬 필요가 있다. 본 연구의 목적은 이부프로펜의 분쇄조건을 최적화하는데 있다. 이부프로펜을 분쇄하기 위하여 유성밀을 사용하였으며, Box-Behnken 방법을 이용하여 분쇄변수들의 최적조건을 구하였다. 이부프로펜 분쇄생성물의 물성을 조사하기 위하여 입도, 결정크기 및 인장강도 측정에는 각각 입도분석기, XRD, tensile/compression tester를 사용하였다. 분쇄 최적조건은 밀회전수는 290 rpm, 시료장입량은 24.6 g, 분쇄시간은 10분이었으며, 이 조건에서 이부프로펜 분쇄생성물의 입도는 $13.5{\mu}m$이었다. 이부프로펜은 분쇄 후 결정크기가 감소하였다. 이부프로펜 분쇄생성물의 정제의 상대밀도가 0.85~0.90인 범위에서 그 정제의 인장강도는 $12{\sim}14Kg_f/cm^2$ 이었다.

Keywords

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