Dipartimento di Scienze del Farmaco

diario delle lezioni | diario esami | lauree

Navigation

Ricerca >> Gruppi di Ricerca >> Scheda pubblicazione

Preparation of solid dispersions of nonsteroidal anti-inflammatory drugs with acrylic polymers and studies on mechanisms of drug-polymer interactions

Abstract

This work studied the mechanisms of interaction between Eudragit RS100 (RS) and RL100 (RL) polymers with 3 nonsteroidal anti-inflammatory drugs: diflunisal (DIF), flurbiprofen (FLU), and piroxicam (PIR). Solid dispersions of polymers and drugs at different wt. ratios were prepd. by coevaporation of their ethanol solns. The resulting coevaporates were characterized in the solid state (Fourier-transformed IR spectroscopy (FT-IR) IR, differential scanning calorimetry, powder-x-ray diffractometry) as well as by studying the in vitro drug release in a gastroenteric environment. Absorption tests from drug solns. to the solid polymers were also performed to better explain the mechanism of interactions between them. The preparative conditions did not induce changes in the cryst. state of the drugs (amorphization or polymorphic change). Drugs strongly interacted with the ammonium groups present in polymers, giving an electrostatic interaction that reinforced the mere phys. dispersion of drug mols. within polymer networks. Such interactions are related to the chem. structure of the drugs and to their dissocd. or undissociated state. The dispersion of drugs in the polymer matrixes strongly influenced their dissoln. rate, which appeared slower and more gradual than those of the pure drugs, when polymer ratios were increased. RL coevaporates usually displayed higher dissoln. rates. The kinetic evaluation of the dissoln. profile, however, suggested that both the drug soly. in the external medium and its diffusion capacity within the polymer network are involved. In the sorption expts., RL showed a greater adsorptive capacity than RS, in relation to the greater no. of quaternary ammonium functions, which behave as activity sites for the electrostatic interactions. In the presence of Tris-HCl buffer (pH 7.4), drug adsorption was reduced, as a consequence of the competition of the chloride ions with drug anions for the polymer binding sites. In general, DIF and FLU displayed a similar interaction with RS and RL active sites; PIR's was different. The different mol. structures of these agents can justify such findings. The presence of a carboxyl group (instead of another dissociable acidic moiety, like the hydroxy-enolic one in the PIR mol.) could help explain the strong interaction with RS and RL polymers' quaternary ammonium centers. Preliminary studies like ours are important in helping develop better forecasting and increasing the understanding of the incorporation/release behavior of drugs from particulate delivery systems that can be made from these polymers.

Autori

PUGLISI - Giovanni

PIGNATELLO - Rosario

Altri Autori

Ferro Marinella