Synthesis of Haloperidol Prodrugs and Their Hydrolysis by Porcine Liver Esterase
Andrew P. Morris,
Keith R. Brain,
Charles M. Heard.
In probing enhancement of the transdermal delivery of the anti-psychotic drug haloperidol, five prodrugs (ethanoate, propanoate, butanoate, octanoate and decanoate) were synthesised and their relative rates of hydrolysis determined in the presence of porcine liver esterase (PLE), a model for cutaneous esterases. H NMR, MS and elemental analysis confirmed the successful synthesis of each prodrug in high purity, and each was found to hydrolyse in the presence of PLE with the hydrolytic rate reaching a maximum with haloperidol octanoate (C8) at 2.31 ± 0.06 nmol ml- h- (p < 0.001).
Keywords: Haloperidol, prodrug, ester, porcine liver esterase, transdermal, hydrolysis
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