Novel aqueous chitosan-based dispersions as efficient drug delivery systems for topical use. Rheological, textural and release studies.

The use of a novel cross-linked thiolated chitosan (CTS) was investigated as the main component of aqueous dispersions (at 1% and 3% w/v) for topical drug delivery systems. The nonionic theophiline (Th) and the cationic diltiazem(.)HCl (Dt) (at 0.5% w/v concentration) were used as model drugs. All aqueous dispersions behaved as viscoelastic fluids. The CTS 1% dispersions showed predominance of viscous component and low viscosity. However, in the CTS 3% dispersions, both the elastic component and high viscosities prevailed. So, texture parameters improved from CTS 1% to 3% dispersions and CTS 3%-Dt showed greater cohesion and adhesion than CTS 3%-Th, but always below CTS alone. All dispersions showed a Fickian diffusion mechanism. Despite release profiles of both drugs almost fully overlapped at 1% CTS, diffusion coefficients confirmed Dt released faster than Th at 3% CTS. The rheological behavior and the chemical nature of the drugs explained these results.

A new biodegradable polythiourethane as controlled release matrix polymer.

The main aim of this paper is the synthesis and characterization of a new linear functional biodegradable polythiourethane-d,l-1,4-dithiothreitol-hexamethylene diisocyanate [PTU(DTT-HMDI)]. The SeDeM diagram has been obtained to investigate its suitability to be processed through a direct compression process. Furthermore, the ability of this polymer to act as controlled release matrix forming excipient has been studied. Four batches of matrices containing 10-40% of polymer and theophylline anhydrous as model drug have been manufactured. Release studies have been carried out using the paddle method and the polymer percolation threshold has been estimated. The principal parameters of the SeDeM Expert system, such as the parametric profile (mean radius) and the good compression index (IGC=4.59) for the polymer are very close to the values considered as adequate for direct compression even with no addition of flow agents. Furthermore, the results of the drug release studies show a high ability of the polymer to control the drug release. The excipient percolation threshold has been estimated between 20% and 30% w/w of polymer.

Synthesis and characterization of a novel chitosan-N-acetyl-homocysteine thiolactone polymer using MES buffer.

We report a new "green" approach to synthesize a novel thiolated chitosan conjugate, chitosan-N-acetyl-homocysteine thiolactone (chitosan-AcHcys) using a "Good's buffers", 2-(N-morpholino)ethanesulfonic acid (MES). After that, the crosslinked Xr-chitosan-AcHcys was obtained only in the presence of air, without other reactants. The chitosan-AcHcys spectrum shows a partial incorporation of the thiolactone onto the polymer backbone. The derivative thermogravimetric analysis confirmed that chitosan-AcHcys is slightly less stable than starting chitosan; however, the peak profile is broadened which is indicative of deeper changes in the thermal degradation process. Also, aqueous dispersions with different concentrations of the crosslinked material (Xr-chitosan-AcHcys) were prepared and rheologically characterized. All aqueous dispersions are viscoelastic fluid with shear-thinning behavior. The viscosity of the dispersions (1-7% of chitosan-AcHcys) increases as a function of polymer concentration. So, we have achieved to disperse a high concentration of thiolated-chitosan derivative in water with different rheological characteristics, which could affect the drug release.