Effects of metal ions on entero-soluble poly(methacrylic acid-methyl methacrylate) coating : a combined analysis by ATR-FTIR spectroscopy and computational approaches
Articolo
Data di Pubblicazione:
2010
Citazione:
Effects of metal ions on entero-soluble poly(methacrylic acid-methyl methacrylate) coating : a combined analysis by ATR-FTIR spectroscopy and computational approaches / F. Cilurzo, C.G.M. Gennari, F. Selmin, G. Vistoli. - In: MOLECULAR PHARMACEUTICS. - ISSN 1543-8384. - 7:2(2010), pp. 421-430. [10.1021/mp900199a]
Abstract:
Poly(methacrylic acid-methyl methacrylate)s (HPMMs) are pH-dependent polymers which ionize and form salts (PMMs) in neutral conditions. Despite their wide use in tablet coating,the interactions of PMMs with electrolytes present in biorelevant media and luminal fluids have been scantly investigated. The data enerated in the current work provide the basic information on the effect of bivalent cations, namely, Ca2+, Zn2+ and Mn2+, on the HPMMs’ solubility and, consequently, on the performances (disintegration and drug dissolution) of acetaminophen gastroresistant tablets when exposed to fluid containing such salts. The interactions between
polymers and metal ions were analyzed by ATR-FTIR spectroscopy and in silico combining molecular dynamics simulations to explore the conformational profiles of several oligomers with
different Mw, taken as model of the polymers, with ab initio and semiempirical calculations in
the gas phase. The computational results agree with the experimental data in terms of spatial
disposition of the bications with respect to PMMs (Ca2+ and Mn2+ as bidentate form and Zn2+
as monodentate ligand) and interaction strength (Zn2+ > Mn2+ > Ca2+). The tablet disintegration
and dissolution rate of acetaminophen were strongly affected by the interactions of the dissolving copolymer with the metal ions which led to coating insolubilization. These preliminary results underline that the ingestion of metal ions at high concentrations could affect the drug liberation from gastroresistant dosage forms.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
F. Cilurzo, C.G.M. Gennari, F. Selmin, G. Vistoli
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