Synchronized release of sulpiride and sodium decanoate from HPMC matrices:A rational approach to enhance sulpiride absorption in the rat intestine

Purpose. (a) To improve the absorption of sulpiride (SP) through the intest inal wall by incorporating it together with sodium decanoate (SD) into erod ible matrices, designed to synchronize the release of SP and SD over differ ent periods of time; (b) to test, in vivo the hypothesis that this simultan eous release increases SP absorption from the intestinal lumen. Methods. Matrix tablets, possessing different erosion rates, were pre Dared by changing the ratios between SD and hydroxypropyl methylcellulose (HPMC) . The amounts of HPMC varied from 2.5% to 17% w/w. Double layer tablets, co ntaining similar amounts of SP, SD, and HPMC were used as nonsynchronous co ntrols. The erosion kinetics of the tablets was assessed gravimetrically in vitro in USP basket dissolution apparatus and in vivo in the intestine of the anesthetized rat after intra-intestinal administration. SP absorption w as studied after intra-intestinal administration of the different kinds of tablets to anesthetized rats, by monitoring SP blood levels. SP and SD leve ls in the withdrawn samples from the dissolution systems and blood were ana lyzed by HPLC. Results. The controlled erosion of the tablets resulted in equal release ra tes of SP and SD during the initial lineal phase of the process. This synch ronized release lasted over different time periods depending on the relativ e amount of HPMC in the formulations (from 1 hour to 4 hours for 2.5 and 17 % w/w of HPMC, respectively). The synchronous matrices increased SP bioava ilability after intra-intestinal administration. The increase varied from 1 .4 to 2.3-fold for the slow and the fast release formulations, respectively (compared with the nonsynchronous, SD containing control formulations), in dicating the ability to control both erosion rate and length of intestinal segment in which absorption is taking place. Conclusions. SP bioavailability alter intestinal administration can be impr oved only if SP is released together with SD along the entire intestinal ro ute. This can he accomplished by the design of synchronous matrices capable of concomitant release of SP and SD despite the differences in their water solubility. The ability to manipulate and control the duration of the sync hronous phase of the matrices makes it possible for SP to be absorbed at di fferent parts of the intestine.