SYNTHESIS OF PARACETAMOL-PEG PRODRUGS, IN-VITRO AND IN-VIVO EVALUATIONAbstract
Paracetamol is a well-known drug for its antipyretic, analgesic and anti-inflammatory activity. The drug being an OTC had been used more frequently than required. As a result of this overdosage of the drug caused a hepatotoxic effect. So to overcome this, an approach of PEGylation was chosen. PEG 1500-Paracetamol, PEG 6000-Paracetamol, PEG 1500-Glycine-Paracetamol, and PEG 6000-Glycine- Paracetamol. The Prodrugs synthesized were subjected to in- vitro dissolution at λmax 256nm at pH 1.2, 4.5 and 6.8. The studies revealed that % drug release was more at pH 6.8 rather than at pH 1.2 and 4.5, for PEG 6000-Gly-Paracetamol than PEG 1500-Gly-Paracetamol and also PEG 6000-Paracetamol % drug release was more than PEG 1500-Paracetamol. In-vivo Analgesic activity by Tail Immersion method revealed that PEG 6000-Gly-Paracetamol and PEG 1500-Gly-Paracetamol has higher analgesic activity than PEG-PEG 6000-Paracetamol and PEG 1500-Paracetamol, which indicates the influence of spacer, i.e., Glycine on drug release. In-vivo Analgesic activity by hot plate method and acetic acid methods revealed that PEG 6000-Gly-Paracetamol and PEG 6000-Paracetamol has higher analgesic activity than PEG 1500-Gly-Paracetamol and PEG 1500-Paracetamol, which indicates the influence of higher molecular weight on drug release.