Matrix tablets based on thiolated poly(acrylic acid): pH-dependent variation in disintegration and mucoadhesion.
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.
Guggi
Davide
D
Institute of Pharmaceutical Technology and Biopharmaceutics, Center of Pharmacy, University of Vienna, Althanstr. 14, A-1090 Vienna, Austria.
Marschütz
Michaela K
MK
Bernkop-Schnürch
Andreas
A
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
D000180:Acrylic Resins; D013438:Sulfhydryl Compounds; D013607:Tablets; C006903:carbopol 940