Improving the Oral Bioavailability of Sulpiride by Sodium Oleate in Rabbits

Abstract

To improve the limited oral bioavailability of sulpiride, a dosage form containing sodium oleate as an absorption enhancer was developed and evaluated using gastric-emptying-controlled rabbits in a cross-over manner. In addition to the known properties of sodium oleate with respect to modifying the permeability of biomembranes, it was found to be capable of improving the physicochemical properties of sulpiride toward a higher lipophilicity (by ion-pair association) and a higher solubility (by micellar solubilization). Nonetheless, the incorporation of sodium oleate with sulpiride as a mixture filled in hard gelatin capsules failed to increase intestinal absorption, whereas the use of enteric capsules, instead of the hard gelatin capsules resulted in a significant increase (P < 0.05) in the oral bioavailability.

Improving the Oral Bioavailability of Sulpiride by a Gastric-retained Form in Rabbits

“…Combining the results of the present and previous study (Naasani et al 1995), we conclude that both the gastricretained form and the enteric form in combination with sodium oleate are promising approaches for improving the oral bioavailability of sulpiride. However, considering the inter-and intra-subject variance of the gastric emptying and its effect on the release onset from enteric-soluble formulations, the gastric-retained form is superior i n limiting the bioavailability variance, extending the effective plasma levels and thus achieving better therapy.…”

“…Five milliliters of fresh medium was added t o the dissolution vessel immediately to maintain the original volume. The removed samples were directly analysed by HPLC (Naasani et al 1995).…”

“…erratic limited absorption, and a high dependence on the formulation factors (Mizuno et al 1986;Bressolle et a1 1992). In our previous study, a significant increase in the oral bioavailability was achieved by incorporation of sodium oleate as an enhancer in enteric capsules (Naasani et al 1995). It seemed that the mechanism of enhancing the absorption was due to an improvement in the physicochemical properties of sulpiride toward a higher lipophilicity and a higher solubility as well as to a modification of the permeability of the biomembrane.…”

Studies on Intestinal Absorption of Sulpiride (2): Transepithelial Transport of Sulpiride Across the Human Intestinal Cell Line Caco-2.

“…5) Naasani et al 26) reported that sulpiride was extremely hydrophilic at pH 7.4 or less, and it was unlikely to be partitioned into lipophilic media. In the present study, the transepithelial transport and the intracellular accumulation of sulpiride by Caco-2 cell monolayers were temperature dependent and they were enhanced at weakly acidic pH on the apical side, excluding the intracellular accumulation of sulpiride from the basolateral side.…”