Bioavailability of carbamazepine:beta-cyclodextrin complex in beagle dogs from hydroxypropylmethylcellulose matrix tablets.
The bioavailability of a carbamazepine:beta-cyclodextrin (CBZ:betaCD) complex from hydroxypropylmethylcellulose (HPMC) matrix tablets was evaluated in beagle dogs. A solubility study demonstrated the improvement of CBZ aqueous solubility by adding increasing amounts of betaCD. The 1:1 CBZ:betaCD molar ratio was chosen to produce the complex, which was obtained by spray-drying. Matrix tablets were prepared by direct compressing either a CBZ:betaCD complex or a physical mixture of both substances with HPMC. Both matrix formulations displayed a controlled-release profile when compared to the reference formulation (Tegretol CR 200). CBZ presented a significantly higher bioavailability from matrix tablets containing the CBZ:betaCD complex than that obtained from Tegretol CR 200). Although a high inter-subject variability was observed, the results pointed to the feasibility of using betaCD in order to modulate CBZ release and absorption, as well as to reduce the drug dosage maintaining the same plasma levels.
Koester
Letícia S
LS
Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ipiranga 2752, 90610-000 Porto Alegre, RS, Brazil.
Bertuol
Juliana B
JB
Groch
Kátia R
KR
Xavier
Clarissa R
CR
Moellerke
Roseli
R
Mayorga
Paulo
P
Dalla Costa
Teresa
T
Bassani
Valquiria L
VL
D000818:Animals; D001682:Biological Availability; D002220:Carbamazepine / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D004285:Dogs; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D013607:Tablets; D047392:beta-Cyclodextrins / Q000493:pharmacokinetics*
D013607:Tablets; D047392:beta-Cyclodextrins; D002220:Carbamazepine; D065347:Hypromellose Derivatives; D008747:Methylcellulose; C031215:betadex