The release of a nonsteroidal anti-inflammatory drug (NSAID), 4-biphenylacetic acid (BPAA), from alpha,beta-poly(N-hydroxyethyl)-DL-aspartamide (PHEA) hydrogels was tested at different pHs (4 and 7.4) by measuring the drug transfer from loaded hydrogel to dimyristoylphosphatidylcholine (DMPC) liposomes (multilamellar vesicles, MLV), chosen as a biomembrane model. This drug transfer was compared with the transfer from powdered drug and with drug classical. The perturbing effect of pure BPAA on the thermotropic behaviour of DMPC liposomes, in terms of transition temperature shift (Delta T-m) and enthalpy changes (Delta H), was analysed at different pHs (4 and 7.4) by differential scanning calorimetry (DSC) to determine the relation between the variation of the thermodynamic parameters with the BPAA molar fraction. To study drug uptake by void liposomes, calorimetric measurements were performed on suspensions of blank liposomes added to weighed amounts of BPAA-loaded hydrogel as well as free powdered drug, at two pHs (4 and 7.4). The amount of drug transferred to void liposomes from powdered drug or from the drug molecularly dispersed in hydrogel was quantified by comparing the effect (T-m shift of lipid phase transition) caused by the drug released to that caused by free drug previously dispersed in the liposomes. The results were corrected for the drug partition between lipid vesicles and aqueous phase. The calorimetric results, compared with dissolution tests carried out in the absence of DMPC at the same pHs, show that the release depends on BPAA solubility, that, in turn, is a function of pH. Besides, when the drug is dispersed in PHEA hydrogel, the transfer to void liposomes is quicker than the powdered form, at least for the first hours of the experiment. In addition, it is interesting to note that at pH 4, drug transfer kinetics from hydrogel is higher to that observed at pH 7.4, even if the BPAA solubility at acid pH is lower than neutral pH. Then, the used DSC technique allows one to follow the effects of drug released from delivery systems and the following transfer to void biomembrane model. It should represent an innovative in vitro method that can be applied to study the release kinetics directly at a site of drug uptake which mimics a biological system.
|Titolo:||Effect of pH on the transfer kinetics of an anti-inflammatory drug from polyaspartamide hydrogels to a lipid model membrane|
|Autori interni:||CASTELLI, Francesco|
|Data di pubblicazione:||1997|
|Rivista:||JOURNAL OF CONTROLLED RELEASE|
|Appare nelle tipologie:||1.1 Articolo in rivista|