Him Methadone - Poly Amino Acid Macromolecular Prodrug Synthesis And Drug Controlled Release Study

Two kinds of macromolecular prodrugs of metaxalone were synthesized and characterized through various technologies. The controlled release studies in various media were performed.The target compound was synthesized by three steps:(1) Polymerized L-aspartic acid to PSI; (2) modified the side chain by hydroxyalkyl; (3) linked N-Acetyl chloride metaxalonethe to poly [α,β-(N-hydroxyalkyl-DL-aspartamide)]. The six prodrugs were characterized by IR and DSC. The results of drug release studies showed that the release rate of metaxalone from large molecular weight is faster than the small molecular weight under the same condition in pH 1.1,7.4 and 10.0 buffer solutions.Poly benzyl glutamate were prepared by aminolysis reaction of L-glutamic acid, modified by ethanolamine,and got the better water-soluble and biodegradable poly [(2-hydroxyethyl)-L-glutamine]. The target compound was synthesized from poly [(2-hydroxyethyl)-L-glutamine] and intermediate N-Acetyl chloride metaxalonethe. Characterized the three prodrugs by IR and DSCanalysis. The results of drug release studies showed that under the same condition, the macromolecular prodrug can release metaxalone and the increase of drug release rate with the pH increasing in pH 1.1,7.4 and 10.0 buffer solutions.The release studies were performed in pH=8.0 buffer solutions in the present of a-chymotrypsin. With a-chymotrypsin polymer-drug conjugate can released from more amounts of metaxalone compared with its absence. The nine novel prodrugs can improve the pharmacokinetics of metaxalone, particularly by increasing its half-life period.