Pharmaceutical Studies on the Inclusion Complexes of Non-Steroidal Antiinflammatory Drugs with ${\beta}-Cyclodextrin$ (I)

비(非)Steroid 성소염약물(性消炎藥物)과 ${\beta}-Cyclodextrin$과의 Inclusion Complex에 관(關)한 약제학적(藥劑學的) 연구(硏究) (제1보)(第一報)

The interactions of ${\alpha}-cyclodextrin({\alpha}-CyD)$ and ${\beta}-cyclodextrin({\beta}-CyD)$ with several non-steroidal antiinflammatory drugs were studied on the effects of ${\alpha}-$ and ${\beta}-CyD$ on the solubility of the drugs in aqueous medium. Indoprofen, niflumic acid, alclofenac, and naproxen were chosen as representatives of antiinflammatory drugs. The solubility of all drugs studied increased with the addition of ${\beta}-CyD$, while not with glucose or ${\alpha}-CyD$. The increase of the solubility with ${\beta}-CyD$ was considered due mainly to the formation of inclusion complexes between ${\beta}-CyD$ and drugs. From the solubility data, the apparent stability constants K of the complex could be calculated. Ultraviolet absorption and circular dichroism confirmed the inclusion of indoprofen, niflumic acid and naproxen with ${\beta}-CyD$ in the molar ratio of 1 : 1. Inclusion complexes in solid powder form were obtained by the freeze-drying method and the inclusion formation was confirmed again by infrared, diffential thermal analysis, and X-ray diffraction measurements.