Trials of in situ-gelling and mucoadhesive acetaminophen liquid suppository in human subjects

Abstract

For the development of in-situ gelling and mucoadhesive acetaminophen liquid suppository prepared with poloxamers (P 407, P 188) and sodium alginate, the physicochemical characteristics of liquid suppositories [acetaminophen/P 407/P 188/sodium alginate (5/15/19/0–1.0%)] were evaluated. Furthermore, a pharmacokinetic study of acetaminophen from liquid and conventional solid suppositories in human subjects was carried out. The results showed that acetaminophen liquid suppository [acetaminophen/P 407/P 188/sodium alginate (5/15/19/0.6%)] with optimal gelation temperature, gel strength and bioadhesive force had a similar release pattern to conventional suppository. The area under the drug concentration–time curve (AUC), mean residence time (MRT), biological half-life ( t 1/2) and apparent elimination rate constant ( K el) of acetaminophen from liquid suppository were not significantly different from those from conventional suppository. However, liquid suppository gave significantly faster the time to reach the maximum plasma concentration ( T max) and higher the maximum plasma concentration of drug ( C max) of acetaminophen than conventional suppository ( p<0.05). It is concluded that in situ gelling and mucoadhesive acetaminophen liquid suppository, which was easy to administer to the anus and showed faster absorption of acetaminophen in human subjects than conventional suppository, was more comfortable for the patients and therefore, is thought to be a favorable anti-pyretic and analgesic dosage form for infants and children.