Formulation, release characteristics and bioavailability study of oral monolithic matrix tablets containing carbamazepine.
This study examined the release of carbamazepine (CBZ) from hydrophobic (Compritol 888 ATO) and hydrophilic-hydrophobic matrix combination (Compritol 888 ATO-hydroxpropyl methylcellulose, HPMC). Hydrophobic matrix tablets were prepared by hot fusion technique, while hydrophilic-hydrophobic matrix tablets were prepared by wet granulation technique. The properties of the compressed matrix tablets were determined according to the US Pharmacopoeia. Both matrix formulations displayed a controlled-release profile when compared to the reference formulation (Tegretol CR 200). The bioavailability of CBZ formulations and Tegretol CR 200 were evaluated in beagle dogs. Carbamazepine presented a significant higher bioavailability from matrix tablets containing hydrophilic polymer (HPMC) than that obtained from Tegretol CR200. The average inter-subject plasma concentration variability CV% was the least with tablet containing hydrophilic polymer (HPMC) and was the highest with Tegretol CR 200 (33.8 and 54.1, respectively). Analysis of variance applied to log AUC(0-alpha) and log C(max) showed statistical significant differences among the three formulations (P < 0.05). Plotting the fraction of CBZ released in vitro and fraction absorbed showed a statistically significant relationship (R(2) = 0.935-0.975) for the three matrix tablets examined.
Barakat
Nahla S
NS
Department of Pharmaceutics, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Kingdom of Saudi Arabia. nsybarakat@yahoo.com
Elbagory
Ibrahim M
IM
Almurshedi
Alanood S
AS
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002220:Carbamazepine / Q000008:administration & dosage* / Q000097:blood / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics; D004285:Dogs; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D008956:Models, Chemical; D013607:Tablets
D003692:Delayed-Action Preparations; D013607:Tablets; D002220:Carbamazepine