Self microemulsifying drug delivery systems

As described earlier, poor permeability is also one of the major factors that limit oral bio availability of several drugs like atenolol and acyclovir because of which such drugs have to be administered at significantly higher doses than required. Several microemulsion components, for example, oil phases such as oleic acid, mono glycerides of caprylic acid 

3 High degree of pre-systemic and hepatic first-pass metabolism 

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. 

Drug Theraputic use Components In vivo results Reference 

Anethole trithione Chemopreventive Tween 80, Labrasol, Cremophore MCT 2.5-fold BA increment as compared to tablets [89] 

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Pouton, C.W. (2000). Lipid formulations for oral administration of drugs non-emulsify-ing, self-emulsifying, and self-microemulsifying drug delivery systems. European Journal of Pharmaceutical Sciences, 11, S93-S98. 

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. 

The new cyclosporine formulation (Sandimmun Neoral, Novartis Pharmaceuticals Corporation, East Hanover, NJ) is a self-microemulsifying drug delivery system, which consists of the drug in a lipophilic solvent (corn oil), hydrophilic cosolvent (propylene glycol) surfactant and an antioxidant [37]. Upon contact with GI fluids, Sandimmun Neoral readily forms a homogenous, monophasic microemulsion, which allows the absorption of the drug molecules. Unlike Sandimmun, the formation of this microemulsion is independent of bile salt activity, and indeed, studies have shown that the absorption of cyclosporine from the new formulation is much less dependent on bile flow [38] and is unaffected by food intake [39],... 

Yang, S., et al. 2004. Enhanced oral absorption of paclitaxel in a novel self-microemulsifying drug delivery system with or without concomitant use of P-glycoprotein inhibitors. Pharm Res 21 261. 

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. 

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)...

Subramanian, N., Ray, S., Ghosal, S.K., Bhadra, R. and Moulik, S.P. (2004) Formulation design of self-microemulsifying drug delivery systems for improved oral bioavailability of celecoxib. Biol. Pharm. Bull, 27, 1993-1999. 

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. 

Wu, W., Wang, Y. and Que, L. (2006) Enhanced bioavailability of silymarin by self-microemulsifying drug delivery system. Eur. J. Pharm. Biopharm., 63, 288-294. 

Cui, S., Zhao, C., Chen, D. and He, Z. (2005) Self-microemulsifying drug delivery systems (SMEDDS) for improving in vitro dissolution and oral absorption of pueraria lobata isoflavone. Drug Dev. Ind. Pharm., 31, 349-356. 

Borhade, V.B., Nair, H.A., Hegde, D.D., 2009. Development and characterization of self-microemulsifying drug delivery system of tacrolimus for intravenous administration. Drug Dev. Ind. Pharm. 35, 619—630. 

Grove, M., Miillertz, A., 2007. Liquid self-microemulsifying drug delivery systems. In Hauss, D. (Ed.), Liquid self-microemulsifying drug debvery systems. Informa... 

Mukherjee, T., Plakogiannis, F.M., 2010. Development and oral bioavailability assessment of a supersaturated self-microemulsifying drug delivery system (SMEDDS) of albendazole. J. Pharm. Pharmacol. 62, 1112—1120. 

Kalhapure, R. S. Akamanchi, K. G. (2012). Oleic acid based heterolipid synthesis, characterization and application in self-microemulsifying drug delivery system. International Journal of Pharmaceutics, 425(1-2), 9-18. 

Kim, H. J., Yoon, K. A., Hahn, M., Park, E. S., and Chi, S. C. 2000. Preparation and in vitro evaluation of self-microemulsifying drug delivery systems containing idebenone. Drug Development and Industrial Pharmacy, 26, 523-529. 

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