Influence of different parameters on drug release from hydrogel systems to a biomembrane model. Evaluation by differential scanning calorimetry technique.
ABSTRACT A comparative study on the drug release capacity of four water swellable polymeric systems was carried out by differential scanning calorimetry (DSC). The polymeric systems chosen were alpha,beta-polyaspartahydrazide (PAHy) crosslinked by glutaraldehyde (GLU) (PAHy-GLU) or by ethyleneglycoldiglycidylether (EGDGE), (PAHy-EGDGE), polyvinylalcohol (PVA) crosslinked by glutaraldehyde (PVA-GLU) and alpha,beta-poly(N-hydroxyethyl)-DL-aspartamide (PHEA) by gamma irradiation (PHEA-gamma matrices). The degree of crosslinking for PAHy-GLU, PAHy-EGDGE and PVA-GLU samples was about 0.4 and 0.8. These hydrogels were characterized as free of drugs and were loaded with diflunisal (DFN) (approximately 2.5% w/w). Diflunisal, a non-steroidal anti-inflammatory drug, has been chosen as a model drug to be incorporated into polymeric matrices to follow the release processes of a drug from these hydrogels to a model membrane made by unilamellar vesicles of dipalmitoylphosphatidylcholine (DPPC). Differential scanning calorimetry appears to be a suitable technique to follow the transfer kinetics of the drug from the controlled release system to the biomembrane model. The drug releases from all the considered polymeric hydrogels, were compared with the release observed from the drug solid form by examining the effects on the thermotropic behaviour of DPPC unilamellar vesicles. The release kinetics of the drug from hydrogels were followed at 25, 37 and 50 degrees C to evidence the influence of temperature on the drug release and on the successive transfer to biological membrane model. Particularly, it appears evident that the total amount of drug transferred and the release rate are affected by the polymer crosslinking degree (it increases with crosslinking decrease) as well as by the nature of crosslinking agent. In fact, the drug release profiles from PAHy-GLU samples are more differentiated than those from PAHy-EGDGE. The effect of parameters correlating with the properties of starting polymer, such as water-affinity, crystallinity, glass-to-rubber transition temperature and affinity towards drug molecules, has been also evaluated.
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ABSTRACT: A comparative study between the release of Ibuprofen (IBU) from Eudragit RS100® (RS) and RL100® (RL) nanosuspensions as well as the free drug to a biological model membrane, consisting of dimyristoylphosphatidylcholine (DMPC) multilamellar vesicles (MLV), was carried out by DSC technique. The aim was to assess the suitability of such calorimetric technique to determine the kinetics of drug release from a polymer system, compared with a classical release test by dialysis method. Nanosuspensions were prepared by a modification of the quasi-emulsion solvent diffusion technique (QESD), a particular approach to the general solvent-change method. This kind of system was planned for the ophthalmic release of non-steroidal anti-inflammatory drugs in ocular diseases associated with inflammatory processes (i.e. post-cataract surgery or uveitis). The drug release was monitored by differential scanning calorimetry (DSC), following the effects exerted by IBU on the thermotropic behaviour of DMPC multilamellar vesicles. IBU affects the main transition temperature (Tm) of phospholipid vesicles, causing a shift towards lower values, driven by the drug fraction entering the lipid bilayer. The obtained values have been used as a calibration curve. DSC was performed on suspensions of blank liposomes added to fixed amounts of unloaded and IBU-loaded Eudragit RS100® and RL100® nanosuspensions as well as to powdered free drug. The Tm shifts caused by the drug released from the polymer system or by the free drug, during incubation cycles at 37°C, were compared to the calibration curve in order to obtain the fraction of drug released. The results were also compared with in vitro dialysis release experiments. The suitability of the two different techniques to follow the drug release as well as the differences between the RL and RS polymer systems was compared, confirming the efficacy of DSC for studying the release from polymer nanoparticulate systems. Explanation of the different rate of kinetic release could be due to void liposomes, which represent a better up-taking system than the aqueous solution phase in the dialysis experiments.Thermochimica Acta 04/2003; 400(1):227-234. · 2.11 Impact Factor
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ABSTRACT: The transfers of tetraethylammonium (TEA+) and protonated triflupromazine (HTFP+) through a hydrogel/liquid interface (g/o) and a liquid/liquid interface (w/o) were compared using cyclic voltammetry. After the two phases were put in contact, the behavior of each molecule was analyzed at different pH values and at different time points. The gel induces hydrophobic and electrostatic interactions with TEA+ and HTFP+, shifting the peak potentials to more positive values. The diffusion coefficients, D, in both phases (g and w) at different pH values were calculated. In the case of TEA+, the D value remains constant in both systems. However, the D value of HTFP+ is lower in the gel phase than in the liquid phase.HTFP+ is transferred from the aqueous phase to the organic phase via a direct mechanism that involves coupled acid–base and partition processes. At the g/o interface, the coupled chemical reactions of HTFP+ were inhibited by the drug/gel interaction. The results demonstrate that the g/o system could be used as a model to study the controlled release of charged drugs.Electrochimica Acta 02/2010; 55(7):2409-2413. · 4.09 Impact Factor
- Journal of The American College of Cardiology - J AMER COLL CARDIOL. 01/2011; 57(14).