Pak. J. Pharm. Sci., Vol.24, No.2, April 2011, pp.113-121 113 INTESTINAL PERMEABILITY STUDIES OF SULPIRIDE INCORPORATED INTO SELF-MICROEMULSIFYING DRUG DELIVERY SYSTEM (SMEDDS) MALLIKARJUN CHITNENI 1,2 *, KOK KHIANG PEH 2 , YUSRIDA DARWIS 2 , MUTHANNA ABDULKARIM 2 , GHASSAN ZUHAIR ABDULLAH 2 AND MOHAMMED JAVED QURESHI 1 1 Department of Pharmaceutical Technology, School of Pharmacy and Health Sciences, International Medical University, Kuala Lumpur, Malaysia 2 Department of Pharmaceutical Technology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia ABSTRACT The objective of the present study was to determine the intestinal absorption of sulpiride incorporated into SMEDDS by means of single-pass intestinal perfusion method (SPIP) in rat and to compare the effective permeability coefficient obtained with that of drug solution and micellar solution. The prepared SMEDDS and micelles formulations were investigated for droplets size. SPIP experiment was performed using the three formulations in three of the secluded regions of the small intestine (duodenum, jejunum, and ileum). The amount of the drug in the samples was estimated by HPLC and the effective permeability coefficients in rats were calculated. The human intestinal permeability was predicted based on rat effective permeability coefficient value. The dilution stability of the formulations was also determined. The average droplet size of SMEDDS and micelles was 9.27 nm and 7.20 nm respectively. The effective permeability coefficient of sulpiride was appreciably lower in the ileum weighed against jejunum and duodenum when administered as a solution (p<0.05). The estimated human absorption of sulpiride for the SMEDDS dilutions was superior to that from solution (p<0.05) and similar to micellar solution. The micellar dilutions were unstable whereas the SMEDDS dilutions were stable. Based on the above results, SMEDDS can be a potential candidate for improving the peroral absorption of the sulpiride. Keywords: Sulpiride, single-pass intestinal perfusion technique, SMEDDS, micellar solution, effective permeability coefficient. INTRODUCTION Drug molecules which are poorly soluble and moderately and/or poorly permeable are classified under Biopharmaceutic Classification System (BCS); Class IV (Amidon et al., 1995). Drug belonging to this class present a major obstacle for development of dosage form viable for oral administration and in most cases these drugs are administered parenterally by addition of solubility enhancers into the formulation (Sachan et al., 2009). Even though most of the BCS class IV drugs show an outstanding in vitro pharmacological affect at minute concentrations they donot enter the later stages of drug development as they have low solubility and therefore low and variable absorption when administered orally. In this decade a lot of research has been focused on developing, lipid drug delivery systems in order to enhance the oral bioavailability of drugs that are poorly soluble and in particular the self-microemulsifying drug delivery systems (SMEDDS). Generally these systems are isotropic mixtures of oils, surfactants and co-solvents/co- surfactants (Gursoy and Benita, 2004). Once administered into the gastrointestinal system, they are diluted with gastro intestinal fluid and the gastric motility provides the agitation for the formation of a fine oil-in-water (o/w) micro emulsions (SMEDDS) (Shah et al., 1994). The difference between a SEDDS and SMEDDS is that the former when diluted results in a droplet size between 100 and 300 nm and the later results in a droplet size of less than 50 nm (Gursoy and Benita, 2004). For drugs which are lipophilic in nature this system would enhance the dissolution rate and therefore might improve the oral bioavailability (Cooney et al., 1998; Porter and Charman, 2001; Shen and Zhong, 2006; Singh et al., 2009). Sulpiride is a drug with proven antipsychotic and antidepressant activity. It is reported to be a selective dopamine D2 antagonist. Erratic absorption of this drug is been reported when given orally and the T max reported was 2 to 6 hours after oral administration. One of the causes for this low oral bioavailability (30%) was poor solubility in water (Parikh et al., 2009). This drug undergoes very minimal metabolism, as shown by the amount excreted in the urine unchanged. About 70% to 90% of i.v dose and 15% to 25% of oral dose is excreted unchanged in the urine. However, most of the drug has been recovered in the feces. The plasma elimination half- life of the drug has been reported to be 6 to 8 hours (Haung et al., 2001). This drug has been reported to be a BCS class IV molecule (Rinaki et al., 2003). Baluom et al. (2001) reported the drug to be a substrate for P- *Corresponding author: e-mail: mallikchitneni@yahoo.com