In vitro and in vivo release of lithium from lithium sulphate-gastrointestinal diffusion system

Abstract

Lithium sulphate-gastrointestinal diffusion system (GDS-Li 2SO 4) provides release of a drug by means of a controlled source of diffusion energy. The GDS-Li 2SO 4 consists of a soluble tablet containing 6 mmol of lithium, surrounded by a cellulose acetate membrane containing a soluble pore-creating agent—gum arable. When the particles of gum arable are partially or fully removed from the coating film, the cellulose acetate film which remains is of a porous nature, thus controlling the diffusion rate of the drug. The resultant 12-hours system with a membrane mass of 30–33 mg releases in vitro about 93% of the lithium at a mean constant rate of 0.644 mmol h −1 during 8 hours. Furthermore, the release rate of the lithium can be varied by changing the mass of the membrane. An in vivo study shows that application of the GDS-Li 2SO 4 at intervals of 12 hours is a suitable way to maintain a constant serum level of lithium. The variability of the serum lithium concentration at steady state is expressed as the dosage form index, defined as the ratio of the maximum to minimum concentrations of the drug in serum over 12 hours (DI 12). The low value of the DI 12 (1.16±0.04) indicates that the GDS-Li 2SO 4 is expected to have a high efficacy and reduced side effects. Similar results have been obtained using the lithium sulphate-gastroin-testinal therapeutic system (GIS-Li 2SO 4), in the form of an elementary osmotic pump, but the method of obtaining the GDS-Li 2SO 4 is more simple than the GTS-Li 2SO 4 described previously.