Sustained-release tablets of indomethacin-loaded microcapsules: preparation, in vitro and in vivo characterization.
Indomethacin (IDM) was encapsulated in gelatin-cellulose acetate phthalate (CAP) microcapsules (A) by complex coacervation method and in CAP microcapsules (B) by simple coacervation method. Microcapsules A and B, having mean diameters of 38.24 and 35.74 microm, respectively, were used to prepare sustained-release tablets A and B. The activation energy of thermal degradation for tablets A and B was calculated based on differential scanning calorimetry (DSC) to be 258.9 and 284.8 kcal/mol, respectively. In vitro release profiles showed no burst effect and release t(1/2) of the two sustained-release tablets were found to be 41.30+/-1.86 and 33.25+/-2.84 min, respectively, while that of IDM plain tablets C was 6.30+/-0.39 min (P<0.01). In vitro release of IDM from tablets A and B could be described by Higuchi equation and zero-order kinetics, respectively. After per os (po) administration with physiological saline, their irritation to rat stomach was obviously reduced in comparison with tablets C. Pharmacokinetic study in rabbits showed that t(max) was delayed and C(max) lowered compared with tablets C and the values of AUC(0-24 h) of the three tablets were very close.
Lu
Bin
B
West China School of Pharmacy, Sichuan University, Chengdu 610041, China. lubin@wcums.edu.cn
Wen
Rong
R
Yang
Hong
H
He
Yingju
Y
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000633:toxicity; D019540:Area Under Curve; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002214:Capsules; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D005780:Gelatin / Q000737:chemistry; D006207:Half-Life; D007213:Indomethacin / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000633:toxicity; D007700:Kinetics; D008297:Male; D008956:Models, Chemical; D010316:Particle Size; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013276:Stomach Ulcer / Q000139:chemically induced; D013678:Technology, Pharmaceutical; D013696:Temperature; D013816:Thermodynamics
D000893:Anti-Inflammatory Agents; D002214:Capsules; D003692:Delayed-Action Preparations; D005079:Excipients; D005780:Gelatin; D002482:Cellulose; C011708:cellulose acetate phthalate; D007213:Indomethacin