In Vitro – In Vivo Evaluation of Sustained – Release Lithium Carbonate Matrix Tablets: Influence of Hydrophilic Matrix Materials

Abstract

Background: Conventional Lithium carbonate (LC) tablets produce rapid and relatively high peak blood levels resulting in adverse effects. These drawbacks can be overcome by designing a suitable sustained or controlled-release LC preparation. Methods: Sustained-release matrix tablets were therefore developed using different types and ratios of polymers including carbomer (CP), Na carboxymethylcellulose (Na CMC) and hydroxypropylmethylcellulose (HPMC), to assess the release profiles and in vivo performance of the formulations. The tablets were prepared by either direct compression (DC) or wet granulation (WG). In the DC method, 69% (450 mg) LC, 5, 10 or 15% CP or Na CMC (of total tablet weight), lactose and /or Avicel (to maintain constant tablet weight) were mixed and directly compressed. In the WG method, 450 mg LC and 10, 20, or 30% HPMC were granulated with Eudragit S100 solution, dried, and then compressed to formulate the tablets. In vitro and in vivo, newly formulated sustained-release LC tablets were compared with sustained-release commercial tablets (Eskalith and Priadel). In vivo studies were conducted in nine healthy subjects in a cross-over design, with a 3x3 Latin square sequence, and 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. In vivo, this formulation produced a smooth and extended absorption phase very much similar to that of Eskalith with the identical elimination half-life and extent of absorption. Conclusion: The matrix tablets containing 15% CP reduces the incidence of side effects often associated with high serum concentration of Lithium and blood level variations. Direct correlation between the dissolution profiles and the relative bioavailability of the formulations could be observed.
Keywords: Lithium carbonate, Matrix tablets, Sustained-release, In vitro-in vivo evaluation