The study was aimed at developing a self-microemulsifying drug delivery system (SMEDDS) of Ibuprofen for investigating its intestinal transport behavior using the single-pass intestinal perfusion (SPIP) method in rat. Methods. Ibuprofen loaded SMEDDS (ISMEDDS) was developed and was characterized. The permeability behavior of Ibuprofen over three different concentrations (20, 30, and 40？μg/mL) was studied in each isolated region of rat intestine by SPIP method at a flow rate of 0.2？mL/min. The human intestinal permeability was predicted using the Lawrence compartment absorption and transit (CAT) model since effective permeability coefficients ( ) values for rat are highly correlated with those of human, and comparative intestinal permeability of Ibuprofen was carried out with plain drug suspension (PDS) and marketed formulation (MF). Results. The developed ISMEDDS was stable, emulsified upon mild agitation with 44.4？nm ± 2.13 and 98.86% ± 1.21 as globule size and drug content, respectively. Higher in colon with no significant difference in jejunum, duodenum, and ileum was observed. The estimated human absorption of Ibuprofen for the SMEDDS was higher than that for PDS and MF . Conclusion. Developed ISMEDDS would possibly be advantageous in terms of minimized side effect, increased bioavailability, and hence the patient compliance. 1. Introduction In recent years, much attention has been focused on using emulsion drug delivery system for the purpose of improving the solubility and oral absorption of poorly water-soluble drugs [1–3]. SMEDDSs are defined as isotropic mixtures of natural or synthetic oils, solid or liquid surfactants, or, alternatively, one or more hydrophilic solvents and cosolvents/surfactants that have a unique ability of forming fine oil-in-water (o/w) microemulsions upon mild agitation followed by dilution in aqueous media, such as GI fluids [4]. SMEDDSs spread readily in the GI tract, and the digestive motility of the stomach and the intestine provide the agitation necessary for self-emulsification. SMEDDS is optically clear and thermodynamically stable system with a droplet size less than 100？nm. This system has been shown to improve absorption of drugs due to small droplet size and promotes intestinal lymphatic transport due to its specific components [5]. Ibuprofen (2-(4-(2-methylpropyl)phenyl) propanoic acid) is a nonsteroidal anti-inflammatory drug (NSAID) used for relief of symptoms of arthritis and fever. Ibuprofen is a poor water-soluble drug, and absorption in rats was shown to occur mainly from the intestine and to a lesser,
References
[1]
N. H. Shah, M. T. Carvajal, C. I. Patel, M. H. Infeld, and A. W. Malick, “Self-emulsifying drug delivery systems (SEDDS) with polyglycolyzed glycerides for improving in vitro dissolution and oral absorption of lipophilic drugs,” International Journal of Pharmaceutics, vol. 106, no. 1, pp. 15–23, 1994.
[2]
W. Wu, Y. Wang, and L. Que, “Enhanced bioavailability of silymarin by self-microemulsifying drug delivery system,” European Journal of Pharmaceutics and Biopharmaceutics, vol. 63, no. 3, pp. 288–294, 2006.
[3]
T. R. Kommuru, B. Gurley, M. A. Khan, and I. K. Reddy, “Self-emulsifying drug delivery systems (SEDDS) of coenzyme Q10: formulation development and bioavailability assessment,” International Journal of Pharmaceutics, vol. 212, no. 2, pp. 233–246, 2001.
[4]
J.-L. Tang, J. Sun, and Z.-G. He, “Self-emulsifying drug delivery systems: strategy for improving oral delivery of poorly soluble drugs,” Current Drug Therapy, vol. 2, no. 1, pp. 85–93, 2007.
[5]
W. N. Charman and V. J. Stella, “Transport of lipophilic molecules by the intestinal lymphatic system,” Advanced Drug Delivery Reviews, vol. 7, no. 1, pp. 1–14, 1991.
[6]
S. G. Kapsi and J. W. Ayres, “Processing factors in development of solid solution formation of Ibuprofen for enhancement of drug dissolution and bioavailability,” International Journal of Pharmaceutics, vol. 229, pp. 193–203, 1999.
[7]
L. Salphati, K. Childers, L. Pan, K. Tsutsui, and L. Takahashi, “Evaluation of a single-pass intestinal-perfusion method in rat for the prediction of absorption in man,” Journal of Pharmacy and Pharmacology, vol. 53, no. 7, pp. 1007–1013, 2001.
[8]
N. Kaewnopparat, S. Kaewnopparat, A. Jangwang, D. Maneenaun, and T. Chuchome, “Increased solubility, dissolution and physicochemical studies of curcumin-polyvinylpyrrolidone K-30 solid dispersions,” World Academy of Science, Engineering and Technology, vol. 55, pp. 229–234, 2009.
[9]
R. Aboofazeli and M. J. Lawrence, “Investigations into the formation and characterization of phospholipid microemulsions. II. Pseudo-ternary phase diagrams of systems containing water-lecithin-isopropyl myristate and alcohol: influence of purity of lecithin,” International Journal of Pharmaceutics, vol. 106, no. 1, pp. 51–61, 1994.
[10]
B. M. Patel, S. Mandal, and K. S. Rajesh, “Formulation and kinetic modeling of curcumin loaded intranasal mucoadhesive microemulsion,” Journal of Pharmacy and Bioallied Sciences, vol. 4, no. 5, pp. 81–83, 2012.
[11]
A. A. Date and M. S. Nagarsenker, “Design and evaluation of microemulsions for improved parenteral delivery of propofol,” AAPS PharmSciTech, vol. 9, no. 1, pp. 138–145, 2008.
[12]
D. Patel and K. K. Sawant, “Oral bioavailability enhancement of acyclovir by self-microemulsifying drug delivery systems (SMEDDS),” Drug Development and Industrial Pharmacy, vol. 33, no. 12, pp. 1318–1326, 2007.
[13]
T. J. Cook and S. S. Shenoy, “Intestinal permeability of chlorpyrifos using the single-pass intestinal perfusion method in the rat,” Toxicology, vol. 184, no. 2-3, pp. 125–133, 2003.
[14]
P. Zakeri-Milani, H. Valizadeh, H. Tajerzadeh et al., “Predicting human intestinal permeability using single-pass intestinal perfusion to rat,” Journal of Pharmacy and Pharmaceutical Sciences, vol. 10, no. 3, pp. 368–379, 2007.
[15]
J. You, Q.-P. Li, Y.-W. Yu, and F.-D. Cui, “Absorption of zedoary oil in rat intestine using in situ single pass perfusion model,” Acta Pharmacologica Sinica, vol. 39, no. 10, pp. 849–853, 2004.
[16]
M. Grassi and G. Cadelli, “Theoretical considerations on the in vivo intestinal permeability determination by means of the single pass and recirculating techniques,” International Journal of Pharmaceutics, vol. 229, no. 1-2, pp. 95–105, 2001.
[17]
J. C. Tsao and T. S. Savage, “High-performance liquid chromatographic determination of ibuprofen in bulk drug and tablets,” Drug Development and Industrial Pharmacy, vol. 11, no. 5, pp. 1123–1131, 1985.
[18]
S. C. Sutton, M. T. Rinaldi, and K. E. Vukovinsky, “Comparison of the gravimetric, phenol red, and 14C-PEG-3350 methods to determine water absorption in the rat single-pass intestinal perfusion model,” AAPS PharmSci, vol. 3, no. 3, p. E25, 2001.
[19]
J. M. DeSesso and C. F. Jacobson, “Anatomical and physiological parameters affecting gastrointestinal absorption in humans and rats,” Food and Chemical Toxicology, vol. 39, no. 3, pp. 209–228, 2001.
[20]
U. Fagerholm, M. Johansson, and H. Lennern？s, “Comparison between permeability coefficients in rat and human jejunum,” Pharmaceutical Research, vol. 13, no. 9, pp. 1336–1342, 1996.
[21]
S. Mandal, S. S. Mandal, and K. S. Rajesh, “Development, characterization and evaluation of microemulsion gel for transdermal delivery of furosemide,” Journal of Pharmacy Research, vol. 4, no. 7, pp. 3133–3135, 2011.
[22]
T. Ikegawa, F. Ushigome, N. Koyabu et al., “Inhibition of P-glycoprotein by orange juice components, polymethoxyflavones in adriamycin-resistant human myelogenous leukemia (K562/ADM) cells,” Cancer Letters, vol. 160, no. 1, pp. 21–28, 2000.
[23]
T. Y. Ma, D. Hollander, R. A. Erickson, H. Truong, H. Nguyen, and P. Krugliak, “Mechanism of colonic permeation of inulin: Is rat colon more permeable than small intestine?” Gastroenterology, vol. 108, no. 1, pp. 12–20, 1995.
[24]
L. X. Yu and G. L. Amidon, “A compartmental absorption and transit model for estimating oral drug absorption,” International Journal of Pharmaceutics, vol. 186, no. 2, pp. 119–125, 1999.
[25]
X. Sha, G. Yan, Y. Wu, J. Li, and X. Fang, “Effect of self-microemulsifying drug delivery systems containing Labrasol on tight junctions in Caco-2 cells,” European Journal of Pharmaceutical Sciences, vol. 24, no. 5, pp. 477–486, 2005.
