Formulation of sustained - release lithium carbonate matrix tablets: influence of hydrophilic materials on the release rate and in vitro-in vivo evaluation.
OBJECTIVE
Conventional lithium carbonate (LC) tablets not only produce rapid and relatively high peak blood levels resulting in adverse effects but also should be administered 3 to 4 times daily. These drawbacks can be overcome by designing a suitable sustained-release LC preparation.


METHODS
Sustained-release matrix tablets containing 450 mg LC were developed using different types and ratios of polymers including carbopol (CP), Na carboxymethylcellulose (Na CMC) and hydroxypropylmethylcellulose (HPMC). The tablets were prepared by either direct compression or wet granulation. In vitro and in vivo, newly formulated sustained-release LC tablets were compared with sustained-release commercial tablet (Eskalith CR). In vivo studies were conducted in nine healthy subjects in a cross over design, with a 3 3 Latin square sequence. Pharmacokinetic parameters were estimated using classical methods.


RESULTS
The matrix tablets containing 15% CP exhibited suitable release kinetics and uniform absorption characteristics comparable to that of Eskalith CR. In vivo, this formulation produced a smooth and extended absorption phase very much similar to that of Eskalith CR with the identical elimination half-life and extent of absorption.


CONCLUSIONS
In vitro release studies demonstrated that the releases of LC from all formulated sustained matrix tablets were generally sustained. Na CMC, CP, and HPMC can, therefore, be used to modify release rates of LC in hydrophilic matrix tablets. The sustained release behavior of tablets containing 15% CP prevents high peak blood levels in man and could be given twice daily to promote patient compliance during maintenance therapy.
Emami
Jaber
J
Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran. emami@pharm.mui.ac.ir <emami@pharm.mui.ac.ir>
Tavakoli
Naser
N
Movahedian
Ahmad
A
D000328:Adult; D000928:Antidepressive Agents / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D006801:Humans; D016651:Lithium Carbonate / Q000493:pharmacokinetics*; D008297:Male; D013607:Tablets / Q000493:pharmacokinetics
D000928:Antidepressive Agents; D003692:Delayed-Action Preparations; D013607:Tablets; D016651:Lithium Carbonate