Self-microemulsifying drug delivery system

A self-microemulsifying drug delivery system (SMEDDS) is a drug delivery system that uses a microemulsion achieved by chemical rather than mechanical means. That is, by an intrinsic property of the drug formulation, rather than by special mixing and handling. It employs the familiar ouzo effect displayed by anethole in many anise-flavored liquors. Microemulsions have significant potential for use in drug delivery, and SMEDDS (including so-called "U-type" microemulsions) are the best of these systems identified to date.[1] SMEDDS are of particular value in increasing the absorption of lipophilic drugs taken by mouth.

SMEDDS in research or development include formulations of the drugs anethole trithione,[2] oridonin,[3][4][5] curcumin,[6] vinpocetine,[7][8] tacrolimus,Mitotane,[9][10][11] berberine hydrochloride,[12] nobiletin,[13] piroxicam,[14][15] anti-malaria drugs beta-Artemether[16] and halofantrine,[17][18] anti-HIV drug UC 781,[19][20] nimodipine,[21][22] exemestane,[23] anti-cancer drugs 9-nitrocamptothecin (9-NC)[24] paclitaxel,[25][26] and seocalcitol,[27][28] alprostadil (intraurethral use),[29] probucol,[18][30] itraconazole,[31] fenofibrate,[32] acyclovir,[33] simvastatin,[34][35] xibornol,[36] silymarin,[37][38] alpha-asarone,[39] enilconazole,[19] puerarin (an isoflavone found in Pueraria lobata),[40][41][42][43] atorvastatin,[44][45][46] heparin,[47] carvedilol,[48] ketoconazole,[49] gentamicin,[50] labrasol,[51] flurbiprofen,[52] celecoxib,[53] danazol,[54] cyclosporine,[55] and idebenone.[56]

Actual applications of Self-microemulsifying drug delivery system' (SMEDDS) remain rare. The first drug marketed as a SMEDDS was cyclosporin, and it had significantly improved bioavailability compared with the conventional solution. In the last decade, several SMEDDS loaded with antiviral drugs (ritonavir, saquinavir) were tested for treatment of HIV infection, but the relative improvement in clinical benefit was not significant. The SMEDDS formulation of ritonavir (soft capsules) has been withdrawn in some countries.[57]

Within the last years SMEDDS were also utilized for the oral administration of biologics. Due to ion pairing with appropriate surfactants [58] these mainly hydrophilic macromolecular drugs can be incorporated in the lipophilic phase of SMEDDS. Provided that the oily droplets being formed in the gut are sufficiently stable towards lipases,[59] can permeate the mucus gel layer in sufficient quantities [60] and exhibit permeation enhancing propertis [61] the oral bioavailability of various biologics can be strongly improved [62]

SMEDDS offer numerous advantages: spontaneous formation, ease of manufacture, thermodynamic stability, and improved solubilization of bioactive materials.[1] Improved solubility contributes to faster release rates and greater bioavailability. For many drugs taken by mouth, faster release rates improve the drug acceptance by consumers. Greater bioavailability means that less drug need be used; this may lower cost, and does lower the stomach irritation and toxicity of drugs taken by mouth.

For oral use, SMEDDS may be formulated as liquids or solids, the solids packaged in capsules or tablets. Limited studies comparing these report that in terms of bioavailability liquid SMEDDS are superior to solid SMEDDS,[21] which are superior to conventional tablets.[21][42][47] Liquid SMEDDS have also shown value in injectable (IV and urethral) formulations and in a topical (oral) spray.[36]

See also

References

  1. 1 2 Spernath A; Aserin A (December 2006). "Microemulsions as carriers for drugs and nutraceuticals". Adv Colloid Interface Sci. 128-130: 47–64. doi:10.1016/j.cis.2006.11.016. PMID 17229398.
  2. ↑ Jing Q; Shen Y; Ren F; Chen J; Jiang Z; Peng B; Leng Y; Dong J (November 2006). "HPLC determination of anethole trithione and its application to pharmacokinetics in rabbits". J Pharm Biomed Anal. 42 (5): 613–7. doi:10.1016/j.jpba.2006.05.013. PMID 16824723.
  3. ↑ Zhang P; Liu Y; Feng N; Xu J (May 2008). "Preparation and evaluation of self-microemulsifying drug delivery system of oridonin". Int J Pharm. 355 (1-2): 269–76. doi:10.1016/j.ijpharm.2007.12.026. PMID 18242895.
  4. ↑ Liu Y; Zhang P; Feng NP; Zhang X; Xu J (September 2008). "[Release kinetics of oridonin self-microemulsifying drug delivery system in vitro]". Zhongguo Zhong Yao Za Zhi (in Chinese). 33 (18): 2049–52. PMID 19160780.
  5. ↑ Liu Y; Zhang P; Feng N; Zhang X; Wu S; Zhao J (January 2009). "Optimization and in situ intestinal absorption of self-microemulsifying drug delivery system of oridonin". Int J Pharm. 365 (1-2): 136–42. doi:10.1016/j.ijpharm.2008.08.009. PMID 18782611.
  6. ↑ Cui J; Yu B; Zhao Y; Zhu W; Li H; Lou H; Zhai G (December 2008). "Enhancement of oral absorption of curcumin by self-microemulsifying drug delivery systems". Int J Pharm. 371 (1-2): 148–55. doi:10.1016/j.ijpharm.2008.12.009. PMID 19124065.
  7. ↑ Chen Y; Li G; Wu X; Chen Z; Hang J; Qin B; Chen S; Wang R (January 2008). "Self-microemulsifying drug delivery system (SMEDDS) of vinpocetine: formulation development and in vivo assessment". Biol. Pharm. Bull. 31 (1): 118–25. doi:10.1248/bpb.31.118. PMID 18175953.
  8. ↑ Cui SX; Nie SF; Li L; Wang CG; Pan WS; Sun JP (November 2008). "Preparation and Evaluation of Self-Microemulsifying Drug Delivery System Containing Vinpocetine". Drug Dev Ind Pharm. 35 (5): 1–9. doi:10.1080/03639040802488089. PMID 19040178.
  9. ↑ Borhade VB; Nair HA; Hegde DD (October 2008). "Development and Characterization of Self-Microemulsifying Drug Delivery System of Tacrolimus for Intravenous Administration". Drug Dev Ind Pharm. 35 (5): 1–12. doi:10.1080/03639040802498856. PMID 18979309.
  10. ↑ Borhade V; Nair H; Hegde D (2008). "Design and evaluation of self-microemulsifying drug delivery system (SMEDDS) of tacrolimus". AAPS PharmSciTech. 9 (1): 13–21. doi:10.1208/s12249-007-9014-8. PMC 2976874Freely accessible. PMID 18446456.
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  13. ↑ Yao J; Lu Y; Zhou JP (2008). "Preparation of nobiletin in self-microemulsifying systems and its intestinal permeability in rats". J Pharm Pharm Sci. 11 (3): 22–9. PMID 18801304.
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  19. 1 2 Goddeeris C; Coacci J; Van den Mooter G (May 2007). "Correlation between digestion of the lipid phase of smedds and release of the anti-HIV drug UC 781 and the anti-mycotic drug enilconazole from smedds". Eur J Pharm Biopharm. 66 (2): 173–81. doi:10.1016/j.ejpb.2006.10.005. PMID 17158039.
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