Lauroyldextran and crosslinked galactomannan as coating materials for site-specific drug delivery to the colon.
Lauroyldextran (LD) and crosslinked galactomannan (XGM) were investigated as microbiologically degradable film coating materials for site-specific drug delivery to the colon. LD was used with degrees of substitution between 0.12 and 0.40, and swelling in aqueous media between 195 and 50%, XGM-batches showed swelling between 309 and 520%. Theophylline tablets were coated in a Hüttlin Kugelcoater with coating quantities of 4-17 mg/cm2. Sprayable coating formulations were obtained with 4% aqueous dispersions of XGM or 4% dispersions of LD in a 1:1 mixture of 1-propanol and water with 10% glycerol (based on the polymer) as a plasticizer. Theophylline dissolution was monitored in a USP XXIII paddle dissolution apparatus with buffer pH 5.5. After 4 h, which is an average small intestine transit time, colon conditions were simulated by adding galactomannanase or dextranase, respectively. Results showed similar dissolution rates for all XGMs and high-swelling LDs during the first 4 h and a relatively quick disintegration after enzyme addition. Both parameters decreased with increasing coating quantities. Dissolution from low-swelling lauroyldextrans was very low but no disintegration was observed after enzyme addition. The disintegration rate was found to be proportional to the square root of the enzyme activity. All swollen materials exhibited low mechanical stability. XGM coatings, especially at higher coating quantities, showed small transient ruptures at the edges not caused by enzyme addition. This behaviour was explained by internal stress due to the high degree of swelling. In principle, materials of both types proved to be suitable as degradable coating materials. The ideal zero-dissolution before and quick disintegration after enzyme addition, however, was not realized with the present materials.
Hirsch
S
S
Freiburger Materialforschungszentrum, Albert-Ludwigs-Universität Freiburg, Germany.
Binder
V
V
Schehlmann
V
V
Kolter
K
K
Bauer
K H
KH
D001673:Biodegradation, Environmental; D003106:Colon / Q000378:metabolism*; D003432:Cross-Linking Reagents; D003910:Dextranase; D003911:Dextrans / Q000737:chemistry*; D016503:Drug Delivery Systems; D004355:Drug Stability; D005690:Galactose / Q000031:analogs & derivatives; D008351:Mannans / Q000737:chemistry*; D008361:Mannosidases; D013608:Tablets, Enteric-Coated; D013806:Theophylline / Q000008:administration & dosage*
D003432:Cross-Linking Reagents; D003911:Dextrans; D008351:Mannans; D013608:Tablets, Enteric-Coated; C012990:galactomannan; D013806:Theophylline; D008361:Mannosidases; C109435:galactomannanase; D003910:Dextranase; D005690:Galactose