Carfentanil (CFTN), a derivative of fentanyl, is highly effective as an analgesic, but its relatively poor solubility in water has limited its nasal application. The objective of this study was to develop the new CFTN-CD inclusion technology to increase the solubility of CFTN. The inclusion compound CFTN-DM-β-CD was prepared by the ultrasonic method and characterized using X-ray powder diffraction and morphological shapes analysis (the scanning electron microscopy). The in vitro dissolution profiles of CFTN-DM-β-CD were assessed in hydrochloric acid and phosphate buffer. Nasal ciliotoxicity studies were carried out using isolated toad palate. Rats were treated with CFTN-DM-β-CD (250 µg/kg) by intravenous, intramuscular injection, oral, or nasal drops. The results showed that CFTN was successfully enveloped by DM-β-CD. The in vitro cumulative dissolution of CFTN-DM-β-CD was obviously enhanced compared to free CFTN in two buffers. Nasal ciliotoxicity studies have shown that the CFTN-DM-β-CD does not exhibit higher nasal ciliotoxicity than that of free CFTN. Pharmacokinetic studies demonstrated that CFTN-DM-β-CD by nasal administration was absorbed more rapidly and has higher Cmax and bioavailability than that of either intramuscular injection or oral administration. In conclusion, the CFTN-DM-β-CD nasal spray was shown to be a relatively safe dosage form for the rapid and effective intranasal delivery of CFTN.
Keywords: Carfentanil; ciliotoxicity; cyclodextrin inclusion; nasal; pharmacokinetics.