Physico-chemical interaction patterns of oxidized polyvinyl alcohol fraction with 4- and 5-aminosalicylic acids

The interaction of the oxidized fraction of polyvinyl alcohol (OF of PVA) with 4- and 5-aminosalicylic acids (4- and 5-ASA) in aqueous solutions was examined by ultraviolet spectroscopy. OF of PVA is obtained by oxidation of polyvinyl alcohol in an aqueous medium affected by hydrogen peroxide (363 K, [PVA] = 3.5% wt., [H2O2] = 1 mol/l, toxid. = 45 min), further separated from the solution by acetone addition. The average molecular weight of the oxidized fraction of PVA, calculated from the experimentally found value of the characteristic viscosity using the Mark-Kun-Houwink equation, amounted to 4.5 kDa. It was found that the addition of the original (non-oxidized) polyvinyl alcohol to aqueous solutions of 4- and 5-ASA does not change their UV spectra. At the same time, the introduction of an oxidized fraction of polyvinyl alcohol into aqueous solutions of aminosalicylic acids leads to spectral changes, indicating intermolecular interactions and complexation. By the method of molar ratios, it was shown that in dilute aqueous solutions OF of PVA forms complex 1 : 1 compounds with 4-ASA and 5-ASA, i.e., one molecule of 4- or 5-aminosalicylic acid accounts for one carboxyl group of the oxidized PVA fraction. Using this method, in the 291-316 K temperature range, the stability constants (K) of the resulting complex compounds were calculated. The results analised demonstrated that the oxidized fraction of polyvinyl alcohol forms strong enough complexes with 4- and 5-aminosalicylic acids: the K values in the temperature range under study vary within (1-7)∙104 l/mol. It was found out that with increasing temperature, the values of stability constants of complex compounds decrease. The study of the temperature dependence of K made it possible to determine the standard values of the changes in the Gibbs energy (ΔG°), enthalpy (ΔH°), and entropy (ΔS°) of complexing. Negative values of thermodynamic parameters indicate a spontaneous process of formation of complexes, their exothermicity and the resulting constraints of the movements of molecules.

Mesalazina: profilo farmacologico, terapeutico e farmacoeconomico

The term inflammatory bowel diseases (IBD) refers to two distinct clinical entities: Crohn.s disease and ulcerative cholitis, two chronic and non-specific disorders of unknown origin. Although quite uncommon and usually not life-threatening, IBDs have a strong economical impact, as they tend to affect patients in high productivity ages and require long and demanding therapies, medical and sometimes surgical. The pharmacological approaches to IBD treatment include aminosalicylates, corticosteroids and immunosuppressive agents. Aminosalicylic acids are the most widely used agents for maintaining remission and for the cure of mild-tomoderate forms of IBDs. This paper outlines the main pharmacological and clinical properties of one of these drugs, mesalamine (mesalazine). Mesalamine is the active moiety of sulfasalazine, an effective but not always tolerated agent. Mesalamine is available in several pharmaceutical forms, to be administered either by the oral or by the rectal route. As the therapeutic action of aminosalicylates is ascribed to their topical action on the inflamed intestine, while the adverse effects are believed to be caused by the systemically adsorbed (mainly in the first tract of the small bowel) fraction, slow-release formulations are usually preferred. From an economical point of view, mesalamine appears to have a moderate acquisition cost, widely offset by the savings induced on direct sanitary and, most importantly, indirect costs of IBDs. In particular, the availability of a generic drug with advanced colon-delivery technology provides the physician with the opportunity to treat patients with the best available technology at a reasonable price.