Properties of hot-melt extruded tablet formulations for the colonic delivery of 5-aminosalicylic acid.
Hot-melt extruded tablets were prepared using Eudragit S 100 as the polymeric carrier to target delivery of 5-aminosalicylic acid (5-ASA) to the colon. Scanning electron microscopy, modulated differential scanning calorimetry and X-ray diffraction analysis of the hot-melt tablet extrudates demonstrated that 5-ASA remained crystalline and was homogeneously dispersed throughout the polymer matrix. A pre-plasticization step was necessary when incorporating triethyl citrate (TEC) into the formulation in order to achieve uniform mixing of the polymer and plasticizer, effectively reduce the polymer glass transition temperature (T(g)), and to lower the processing temperatures. The concentration of TEC in the extrudates not only influenced the processing temperature, but also influenced the drug release rates from the extruded tablets due to leaching of the TEC during dissolution testing. Citric acid monohydrate was found to plasticize Eudragit S 100, and when combined with TEC in the powder blend, the temperatures required for processing were reduced. Tablets containing citric acid released drug at a slower rate as a result of the suppression of polymer ionization due to a decrease in the micro-environmental pH of the tablet. The drug release profiles of the extruded tablets were found to fit both diffusion and surface erosion models.
Bruce
L Diane
LD
Quintiles, Inc., Kansas City, MO 64137, USA. diane.bruce@quintiles.com
Shah
Navnit H
NH
Malick
A Waseem
AW
Infeld
Martin H
MH
McGinity
James W
JW
D002626:Chemistry, Pharmaceutical; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D019804:Mesalamine / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D013607:Tablets
D013607:Tablets; D019804:Mesalamine