SMEDDS

Niro GA, Ciancio A, Tillman HL, Lagget M, OUvero A, Pern F, Fontana R, Little N, Campbell F, Smedde A, Manns MP, Andriulli A, Rizzetto M (2005a) Lamivudine therapy in chronic delta hepatitis a multicentre randomized-controUed pilot study. Aliment Pharmacol Ther 22 227-232... 

Cui, S., Zhao, C., Chen, D., He, Z. (2005). Self-microemulsilying drug delivery systems (SMEDDS) for improving in vitro dissolution and oral absorption of Pueraria lobata isoflavone. Drug Development and Industrial Pharmacy, 31, 349-356. 

FIGURE 11.7 Comparison of marketed lipid-based cyclosporine formulations, Sandimmune (Olive oil SEDDS) and Neoral (Hydrolyzed Corn oil SMEDDS) in patients. (Adaptedfrom Constantinides, P.P. (1995) Pharm. Res., 12 1561-1572.)... 

Holm, R., Porter, C.J.H., Edwards, GA., Mullertz, A., Kristensen, H.G, and Charman, W.N. (2003) Examination of oral absorption and lymphatic transport of halofantrine in a tripie-cannulated canine model after administration in self-microemulsifying drug delivery systems (SMEDDS) containing structured triglycerides.Eur. J. Pharm. Sci., 20 91-97. 

Paclitaxel is an antitumor drug, with a low oral bioavailability (6%) [96] due to poor water solubility, hydrophobicity (log P = 4), and its high affinity to P-gp and CYP3A4. A novel SMEDDS of paclitaxel increased the bioavailability by up to 1.5-fold in comparison to the commercial micellar solution taxol. Concomitant intake of cyclosporine A, a known P-gp inhibitor, further increased paclitaxel bioavailability (1.8-fold in comparison to taxol) [97]. 

The most recent development (in terms of physicochemical/particle size approaches) in the design of lipid-based delivery systems has been the use of microemulsions, microemulsion preconcentrates, or self-microemulsifying drug delivery systems (SMEDDS), typified by the Sandimmun Neoral formulation. 

Components Medium-chain triglyceride SEDDS (% w/w) Medium-chain triglyceride SMEDDS (% w/w) Long-chain triglyceride SMEDDS (% w/w)... 

Figure 1 The mean (n = 4) plasma concentration versus time profiles of Hf (panel A) and Hfm (panel B) after the oral administration of MCT SEDDS (O), MCT SMEDDS ( ), and LCT SMEDDS (A) formulations of Hf base (50 mg) to fasted beagles. (From Ref. 80.)...

Kang BK, Lee JS, Chon SK, et al. Development of self-microemulsifying drug delivery systems (SMEDDS) for oral bioavailability enhancement of simvastatin in beagle dogs. Int J Pharm 2004 274 65-73. 

Table 2 Bioavailability Parameters Obtained in Male Beagle Dogs (mean SD, n = 3) After Oral Administration of 50 mg of Hf Base Formulated as Either a Long chain Self-microemulsifying Formulation (SMEDDS) or a Medium-chain Self-emulsifying (SEDDS), or Self-microemulsifying Drug Delivery System (SMEDDS)...

Several investigations are reported in the literature describing the utility of the SMEDDS in oral delivery. The major advantages of SMEDDS include improvement in oral bioavailability, quick onset of action [87] and reduction in intra- and inter-individual variability and food effects [88]. Most of the investigations described so far have focused on the pharmacokinetics of the drug to assess oral bioavailability but not on the pharmacodynamic efficacy and the candidates explored so far belong to discrete therapeutic classes. Table 9.5 enlists examples of various SMEDDS reported so far and their in vivo advantage. 

Shen, H.R. and Zhong, M.K. (2006) Preparation and evaluation of self-microemulsifying drug delivery systems (SMEDDS) containing atorvastatin. /. Pharm. Pharmacol., 58, 1183-1191. 

Early work by Pouton demonstrated that a good SEDDS formulation could significantly enhance the dissolution and bioavailability of poorly soluble compounds (113). Pouton proposed two criteria to describe the efficiency of SEDDS formulation (l)the rate of emulsification and (2) the particle size distribution of the resultant emulsion. An efficient SEDDS should produce fine dispersions (<1 gm) rapidly at a reproducible rate. Efficient SEDDS or SMEDDS have demonstrated their potential in delivering hydrophobic compounds. The most notable case is a SMEDDS formulation of cyclosporin A (Neoral), in which the formulation has significantly increased the bioavailability as well as decreased patient variability (114,115). 

This principle of anhydrous concentrates was named SMEDDS , self micro-emulsifying dmg delivery systems. Such formulations lack the aqueous phase. On dilution, a SMEDDS spontaneously converts to an optically clear, thermodynamically stable microemulsion, which contains the dmg in molecular dispersion. The same principle of a water-free concentrate which leads to a macro -emulsion is called SEDDS, a self-emulsifying dmg delivery system. A recent review on self-dispersing lipid based systems was... 

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