Self-assembling poly(vinyl alcohol) derivatives, interactions with drugs and control of release.
The self-assembling properties of poly(vinyl alcohol) substituted with 2-hydroxypropyltrimethylammonium and with acyl chains of different molecular weights (butyryl, capryloyl, lauroyl, or myristoyl) were evaluated to assess the conditions favoring interaction with a poorly soluble drug such as indomethacin to increase its availability. To evaluate the effect of drug-polymer interactions on the solubility of the drug, phase-solubility diagrams were obtained from each substituted polymer at pH 2.0, 5.5, and 7.4 in the presence of indomethacin. To evaluate the availability of the free drug in solution, release profiles of the free drug from drug-polymer physical mixtures were obtained by a dissolution-diffusion apparatus containing a dialysis membrane allowing diffusion of the free drug towards a receiving phase where its concentration was determined over time. The phase-solubility diagrams revealed increasing drug solubility on increasing the polymer concentration. The drug-polymer affinity was slightly increased by lengthening the chain of the substituent on the polymer and was strongly increased by raising the pH of the aqueous phase. The thermodynamic evaluation of the drug-polymer interactions indicated that the interaction is enthalpically driven while the increase in drug-polymer affinity with increasing chain length could be attributed to an entropic contribution. The free drug availability from the drug-polymer systems increased on enhancing the drug-polymer affinity because it corresponded to an increase in the solubilizing effect of the polymer on the drug.
Orienti
I
I
Department of Pharmaceutical Sciences, Bologna University, Via S. Donato 19/2-40127, Bologna, Italy. orienti@biocfarm.unibo.it
Bigucci
F
F
Gentilomi
G
G
Zecchi
V
V
D003692:Delayed-Action Preparations / Q000493:pharmacokinetics; D004347:Drug Interactions; D006367:HeLa Cells; D006801:Humans; D007213:Indomethacin / Q000493:pharmacokinetics; D011108:Polymers / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D011142:Polyvinyl Alcohol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D012995:Solubility; D013816:Thermodynamics
D003692:Delayed-Action Preparations; D011108:Polymers; D011142:Polyvinyl Alcohol; D007213:Indomethacin