Synthesis, characterization and in vitro release of 5-aminosalicylic acid and 5-acetyl aminosalicylic acid of polyanhydride--P(CBFAS).
A novel polyanhydride, poly[(5-carboxybutyl formamide)-2-acetyl salicylic anhydride] (P(CBFAS)), with 5-aminosalicylic acid (5-ASA) incorporated into the polymer backbone was synthesized and characterized by infrared, (1)H-nuclear magnetic resonance, differential scanning calorimetry, vapor pressure osmometry, etc. The polyanhydride was subjected to degradation and simultaneously released 5-ASA and its derivative 5-acetyl aminosalicylic acid (5-acetyl ASA) in vitro under various conditions. The factors influencing the release profiles of 5-ASA and 5-acetyl ASA, including polymer molecular weights, pH value, enzyme and rat gastrointestinal contents, were examined. The results showed that the release rate of 5-ASA and 5-acetyl ASA increases with increasing pH value and with decreasing molecular weights. In PBS (pH 8.0, 37 degrees C) total ASA released was 8.0% for P(CBFAS)(1) (Mn 10770) in 13 h, but only 1.1 and 2.6% at pH 2.0 and 6.5, respectively. Enzymes including pepsin and trypsin, as well as rat gastric and jejunum contents had little effect on the release rate of 5-ASA and 5-acetyl ASA at pH 2.0 and 6.5 (less than 4% in 13 h). However, the release rate of 5-ASA and 5-acetyl ASA was much fast in PBS(pH 8.0) containing 5% of cecal contents, the total ASA released was 13.6% for the polymer in 13 h. Considering the high drug loading of the polymer (50.2% of 5-ASA moieties in the backbones) and the degradation characters, it is possible to reach high local concentration of 5-ASA in the colon site via oral administration. Therefore, P(CBFAS) may be potentially useful in the colon specific delivery of 5-ASA.
Cai
Q X
QX
Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, People's Republic of China.
Zhu
K J
KJ
Chen
D
D
Gao
L P
LP
D000636:Aminosalicylic Acids / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D002432:Cecum / Q000201:enzymology; D004339:Drug Compounding; D004355:Drug Stability; D005559:Formamides / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry; D005766:Gastrointestinal Contents / Q000201:enzymology; D006868:Hydrolysis; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D019804:Mesalamine / Q000008:administration & dosage / Q000737:chemistry*; D008970:Molecular Weight; D011355:Prodrugs / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012459:Salicylates / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry; D013055:Spectrophotometry, Infrared; D013997:Time Factors
D000636:Aminosalicylic Acids; D000893:Anti-Inflammatory Agents; D005559:Formamides; D011355:Prodrugs; D012459:Salicylates; C479760:poly((5-carboxybutyl formamide)-2-acetyl salicylic anhydride); D019804:Mesalamine; C028836:N-acetyl-5-aminosalicylic acid