Synthesis of haloperidol prodrugs and their hydrolysis by porcine liver esterase.

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. (1)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.

Design and evaluation of thin and flexible theophylline imprinted polymer membrane materials.

The aim of this work was to produce a thin, flexible and diffusion able molecularly imprinted polymeric matrix with good template accessibility. Membranes were prepared using a non-covalent molecular imprinting approach and their physical characteristics and binding capabilities investigated. Two materials were used, a poly(tri-ethyleneglycol dimethyacrylate-co-methyl methacrylate-co-methacrylic acid) copolymer containing 14% cross-linker and a monomer (g) to porogen (ml) ratio of 1:0.

Skin permeation and ex vivo skin metabolism of O-acyl haloperidol ester prodrugs.

Ethyl (HE), propyl (HP), butyl (HB), octyl (HO) and decyl (HD) O-acyl esters of haloperidol (HA) were evaluated for permeation across full-thickness human and guinea pig skin. The inclusion of 0.5mgmL(-1) cetrimide as a receptor phase solubilising agent did not significantly alter the barrier properties of the membranes.

From 3D to 2D: a review of the molecular imprinting of proteins.

Molecular imprinting is a generic technology that allows for the introduction of sites of specific molecular affinity into otherwise homogeneous polymeric matrices. Commonly this technique has been shown to be effective when targeting small molecules of molecular weight <1500, while extending the technique to larger molecules such as proteins has proven difficult. A number of key inherent problems in protein imprinting have been identified, including permanent entrapment, poor mass transfer, denaturation, and heterogeneity in binding pocket affinity, which have been addressed using a variety of approaches.

Concentration dependent atrazine-atrazine complex formation promotes selectivity in atrazine imprinted polymers.

An atrazine (ATR) molecularly imprinted polymer (MIP) was prepared using a non-covalent strategy. The affinity and selectivity of the polymer was initially evaluated under non-equilibrium conditions and the polymer was shown to possess good template selectivity. The selectivity of the polymer was further investigated under equilibrium conditions and over a range of concentrations using Scatchard plots and Hill plots and by assessing distribution coefficients and normalised selectivity values.