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Enhanced anti-tumor activity and alleviated hepatotoxicity of clotrimazole-loaded suppository using poloxamer-propylene glycol gel.

Research paper by Chul Soon CS Yong, Jing Ji JJ Xuan, Seung-Hwan SH Paek, Yu-Kyoung YK Oh, Jong-Soo JS Woo, Mann Hyung MH Lee, Jung-Ae JA Kim, Han-Gon HG Choi

Indexed on: 23 Jun '06Published on: 23 Jun '06Published in: International Journal of Pharmaceutics



Abstract

To develop a novel clotrimazole-loaded poloxamer-based suppository with enhanced anti-tumor activity and alleviated hepatotoxicity, the melting point of various formulations composed of P 188 and propylene glycol were investigated. The dissolution and anti-tumor activity of clotrimazole delivered by the poloxamer-based suppository was performed. Furthermore, the hepatotoxicity of clotrimazole was carried out after its rectal administration compared to oral administration in mice. The poloxamer mixtures composed of P 188 and propylene glycol were homogeneous phases. P 188 greatly affected the melting point of poloxamer mixtures. In particular, the poloxamer mixture [P 188/propylene glycol (70%/30%)] with the melting point of about 32 degrees C was a solid form at room temperature and instantly melted at physiological temperature. The ratio of P 188/propylene glycol greatly affected the dissolution rates of clotrimazole from poloxamer-based suppository. Dissolution mechanism analysis showed the dissolution rate of clotrimazole from poloxamer-based suppositories was independent of the time. The clotrimazole-loaded suppository with P 188 and propylene glycol could not irritate or damage the rectal tissues of rats and gave the improved anti-tumor activity in a dose-dependent manner at mouse. Furthermore, its rectal administration decreased the hepatotoxicity compared to oral administration. Thus, the poloxamer-based solid suppository system with clotrimazole/P 188/propylene glycol was an effective rectal dosage form for the treatment of tumors with alleviated adverse effects.