title: Matrix tablets based on thiolated poly(acrylic acid): pH-dependent variation in disintegration and mucoadhesion.
abstract: This study examined the influence of the pH on the mucoadhesive and cohesive properties of polyarcylic acid (PAA) and thiolated PAA. The pH of PAA (molecular mass: 450 kDa) and of a corresponding PAA-cysteine conjugate was adjusted to 3, 4, 5, 6, 7 and 8. The amount of immobilised thiol groups and disulfide bonds was determined via Ellman's reagent. Tablets were compressed out of each pH-batch of both thiolated and unmodified PAA and the swelling behaviour, the disintegration time and the mucoadhesiveness were evaluated. The amount of thiol/disulfide groups per gram thiolated PAA of pH 3 and pH 8 was determined to be 332 +/- 94 micromol and 162 +/- 46 micromol, respectively. The thiolated PAA tablets displayed a minimum four-fold higher water uptake compared to unmodified PAA tablets. A faster and higher water uptake of both polymer types was observed above pH 5. Thiolated polymer tablets showed a 3-20-fold more prolonged disintegration time than unmodified PAA tablets. The cohesiveness of PAA-cysteine conjugate increased at higher pH, whereas the unmodified PAA behaved inversely. A 3-7-fold stronger mucoadhesiveness was observed for the PAA-cysteine conjugate tablets compared to unmodified PAA tablets. For both thiolated and unmodified polymer the mucoadhesiveness was 2-4-fold enhanced below pH 5. The difference in mucoadhesion between the two polymer types was most pronounced at these lower pH values. In this study substantial information regarding the pH-dependence of mucoadhesion and cohesion of unmodified polyacrylates and of thiolated polyacrylates is provided, representing helpful basic information for an ameliorated deployment of these polymers.
authors.affiliation: Institute of Pharmaceutical Technology and Biopharmaceutics, Center of Pharmacy, University of Vienna, Althanstr. 14, A-1090 Vienna, Austria.
authors.forename: Davide
authors.initials: D
authors.lastname: Guggi
authors.forename: Michaela K
authors.initials: MK
authors.lastname: Marschütz
authors.forename: Andreas
authors.initials: A
authors.lastname: Bernkop-Schnürch
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry / Q000493:pharmacokinetics*; D000268:Adhesiveness; D000818:Animals; D006863:Hydrogen-Ion Concentration; D007413:Intestinal Mucosa / Q000378:metabolism*; D012995:Solubility / Q000187:drug effects; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000493:pharmacokinetics*; D013552:Swine; D013607:Tablets
chemical_list: D000180:Acrylic Resins; D013438:Sulfhydryl Compounds; D013607:Tablets; C006903:carbopol 940