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,[9][10][11] mitotane, 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 The SMEDDS formulation of ritonavir (soft capsules) has been withdrawn in some countries.[57]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 properties [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): 603–611. 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): 619–630. 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 2976874. PMID 18446456.
  11. ↑ Borhade VB; Nair HA; Hegde DD; Barhate CR (November 2008). "Development and Validation of HPTLC Method for Estimation of Tacrolimus in Formulations". Drug Dev Ind Pharm. 35 (4): 440–448. doi:10.1080/03639040802430594. PMID 19040177. S2CID 97608266.
  12. ↑ Zhang BE; Lu WB; Chen WW (July 2008). "[Study on self-microemulsifying drug delivery system of Jiaotai Pill active components]". Zhong Yao Cai (in Chinese). 31 (7): 1068–71. PMID 18973026.
  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. doi:10.18433/J3MS3M. PMID 18801304. Archived from the original on 2011-07-06. Retrieved 2009-03-13.
  14. ↑ Attama AA; Nkemnele MO (November 2005). "In vitro evaluation of drug release from self micro-emulsifying drug delivery systems using a biodegradable homolipid from Capra hircus". Int J Pharm. 304 (1–2): 4–10. doi:10.1016/j.ijpharm.2005.08.018. PMID 16198521.
  15. ↑ Zhou XT; Wang J; Wang Y; Sun JY; Nie SF; Pan WS (April 2008). "[Design and in vitro evaluation of self-microemulsifying drug delivery systems for piroxicam]". Yao Xue Xue Bao (in Chinese). 43 (4): 415–20. PMID 18664206.
  16. ↑ Mandawgade SD; Sharma S; Pathak S; Patravale VB (October 2008). "Development of SMEDDS using natural lipophile: application to beta-Artemether delivery". Int J Pharm. 362 (1–2): 179–83. doi:10.1016/j.ijpharm.2008.06.021. PMID 18652886.
  17. ↑ Holm R; Porter CJ; Edwards GA; Müllertz A; Kristensen HG; Charman WN (September 2003). "Examination of oral absorption and lymphatic transport of halofantrine in a triple-cannulated canine model after administration in self-microemulsifying drug delivery systems (SMEDDS) containing structured triglycerides". Eur J Pharm Sci. 20 (1): 91–7. doi:10.1016/S0928-0987(03)00174-X. PMID 13678797.
  18. 1 2 Ljusberg-Wahren H; Seier Nielsen F; Brogård M; Troedsson E; Müllertz A (July 2005). "Enzymatic characterization of lipid-based drug delivery systems". Int J Pharm. 298 (2): 328–32. doi:10.1016/j.ijpharm.2005.02.038. PMID 15979260.
  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.
  20. ↑ Goddeeris C; Van den Mooter G (September 2008). "Free flowing solid dispersions of the anti-HIV drug UC 781 with Poloxamer 407 and a maximum amount of TPGS 1000: investigating the relationship between physicochemical characteristics and dissolution behaviour". Eur J Pharm Sci. 35 (1–2): 104–13. doi:10.1016/j.ejps.2008.06.010. PMID 18644442.
  21. 1 2 3 Yi T; Wan J; Xu H; Yang X (October 2008). "A new solid self-microemulsifying formulation prepared by spray-drying to improve the oral bioavailability of poorly water soluble drugs". Eur J Pharm Biopharm. 70 (2): 439–44. doi:10.1016/j.ejpb.2008.05.001. PMID 18603415.
  22. ↑ Yi T; Wan J; Xu H; Yang X (August 2008). "Controlled poorly soluble drug release from solid self-microemulsifying formulations with high viscosity hydroxypropylmethylcellulose". Eur J Pharm Sci. 34 (4–5): 274–80. doi:10.1016/j.ejps.2008.04.010. PMID 18541418.
  23. ↑ Singh AK; Chaurasiya A; Singh M; Upadhyay SC; Mukherjee R; Khar RK (2008). "Exemestane loaded self-microemulsifying drug delivery system (SMEDDS): development and optimization". AAPS PharmSciTech. 9 (2): 628–34. doi:10.1208/s12249-008-9080-6. PMC 2976939. PMID 18473177.
  24. ↑ Lu JL; Wang JC; Zhao SX; Liu XY; Zhao H; Zhang X; Zhou SF; Zhang Q (August 2008). "Self-microemulsifying drug delivery system (SMEDDS) improves anticancer effect of oral 9-nitrocamptothecin on human cancer xenografts in nude mice". Eur J Pharm Biopharm. 69 (3): 899–907. doi:10.1016/j.ejpb.2008.02.023. PMID 18434109.
  25. ↑ Yang S; Gursoy RN; Lambert G; Benita S (February 2004). "Enhanced oral absorption of paclitaxel in a novel self-microemulsifying drug delivery system with or without concomitant use of P-glycoprotein inhibitors" (PDF). Pharm. Res. 21 (2): 261–70. doi:10.1023/B:PHAM.0000016238.44452.f1. PMID 15032307. S2CID 24590025.
  26. ↑ Kang BK; Chon SK; Kim SH; Jeong SY; Kim MS; Cho SH; Lee HB; Khang G (November 2004). "Controlled release of paclitaxel from microemulsion containing PLGA and evaluation of anti-tumor activity in vitro and in vivo". Int J Pharm. 286 (1–2): 147–56. doi:10.1016/j.ijpharm.2004.08.008. PMID 15501011.
  27. ↑ Grove M; Müllertz A; Nielsen JL; Pedersen GP (June 2006). "Bioavailability of seocalcitol II: development and characterisation of self-microemulsifying drug delivery systems (SMEDDS) for oral administration containing medium and long chain triglycerides". Eur J Pharm Sci. 28 (3): 233–42. doi:10.1016/j.ejps.2006.02.005. PMID 16650738.
  28. ↑ Grove M; Müllertz A; Pedersen GP; Nielsen JL (May 2007). "Bioavailability of seocalcitol III. Administration of lipid-based formulations to minipigs in the fasted and fed state". Eur J Pharm Sci. 31 (1): 8–15. doi:10.1016/j.ejps.2007.01.007. PMID 17383165.
  29. ↑ Lee S; Lee J; Choi YW (April 2008). "Design and evaluation of prostaglandin E1 (PGE1) intraurethral liquid formulation employing self-microemulsifying drug delivery system (SMEDDS) for erectile dysfunction treatment". Biol. Pharm. Bull. 31 (4): 668–72. doi:10.1248/bpb.31.668. PMID 18379060.
  30. ↑ Fatouros DG; Nielsen FS; Douroumis D; Hadjileontiadis LJ; Mullertz A (August 2008). "In vitro-in vivo correlations of self-emulsifying drug delivery systems combining the dynamic lipolysis model and neuro-fuzzy networks". Eur J Pharm Biopharm. 69 (3): 887–98. doi:10.1016/j.ejpb.2008.01.022. PMID 18367386.
  31. ↑ Woo JS; Song YK; Hong JY; Lim SJ; Kim CK (February 2008). "Reduced food-effect and enhanced bioavailability of a self-microemulsifying formulation of itraconazole in healthy volunteers". Eur J Pharm Sci. 33 (2): 159–65. doi:10.1016/j.ejps.2007.11.001. PMID 18178070.
  32. ↑ Patel AR; Vavia PR (2007). "Preparation and in vivo evaluation of SMEDDS (self-microemulsifying drug delivery system) containing fenofibrate". AAPS J. 9 (3): E344–52. doi:10.1208/aapsj0903041. PMC 2751486. PMID 18170981.
  33. ↑ Patel D; Sawant KK (December 2007). "Oral bioavailability enhancement of acyclovir by self-microemulsifying drug delivery systems (SMEDDS)". Drug Dev Ind Pharm. 33 (12): 1318–26. doi:10.1080/03639040701385527. PMID 18097805. S2CID 3119405.
  34. ↑ Kang BK; Lee JS; Chon SK; Jeong SY; Yuk SH; Khang G; Lee HB; Cho SH (April 2004). "Development of self-microemulsifying drug delivery systems (SMEDDS) for oral bioavailability enhancement of simvastatin in beagle dogs". Int J Pharm. 274 (1–2): 65–73. doi:10.1016/j.ijpharm.2003.12.028. PMID 15072783.
  35. ↑ Meng J; Zheng L (September 2007). "Application of mixture experimental design to simvastatin apparent solubility predictions in the microemulsifion formed by self-microemulsifying". Drug Dev Ind Pharm. 33 (9): 927–31. doi:10.1080/03639040601003733. PMID 17891578.
  36. 1 2 Cirri M; Mura P; Mora PC (August 2007). "Liquid spray formulations of xibornol by using self-microemulsifying drug delivery systems". Int J Pharm. 340 (1–2): 84–91. doi:10.1016/j.ijpharm.2007.03.021. PMID 17531411.
  37. ↑ Wu W; Wang Y; Que L (July 2006). "Enhanced bioavailability of silymarin by self-microemulsifying drug delivery system". Eur J Pharm Biopharm. 63 (3): 288–94. doi:10.1016/j.ejpb.2005.12.005. PMID 16527467.
  38. ↑ Woo JS; Kim TS; Park JH; Chi SC (January 2007). "Formulation and biopharmaceutical evaluation of silymarin using SMEDDS". Arch. Pharm. Res. 30 (1): 82–9. doi:10.1007/BF02977782. PMID 17328246. S2CID 22169992.
  39. ↑ Wang DK; Shi ZH; Liu L; Wang XY; Zhang CX; Zhao P (2006). "Development of self-microemulsifying drug delivery systems for oral bioavailability enhancement of alpha-Asarone in beagle dogs". PDA J Pharm Sci Technol. 60 (6): 343–9. PMID 17260899.
  40. ↑ Cui S; Zhao C; Chen D; He Z (May 2005). "Self-microemulsifying drug delivery systems (SMEDDS) for improving in vitro dissolution and oral absorption of Pueraria lobata isoflavone". Drug Dev Ind Pharm. 31 (4–5): 349–56. doi:10.1081/DDC-54309. PMID 16093200.
  41. ↑ Cui S; Zhao C; Tang X; Chen D; He Z (June 2005). "Study on the bioavailability of puerarin from Pueraria lobata isoflavone self-microemulsifying drug-delivery systems and tablets in rabbits by liquid chromatography-mass spectrometry". Biomed. Chromatogr. 19 (5): 375–8. doi:10.1002/bmc.460. PMID 15627278.
  42. 1 2 Yu AH; Zhai GX; Cui J; Liu H (August 2006). "[Preparation of puerarin solid self-microemulsion]". Zhong Yao Cai (in Chinese). 29 (8): 834–8. PMID 17076244.
  43. ↑ Cui SM; Zhao CS; He ZG (June 2007). "[Assessment of Pueraria lobata isoflavone with self-microemulsifying drug delivery systems in vitro and in vivo]". Zhong Yao Cai (in Chinese). 30 (6): 684–7. PMID 17918441.
  44. ↑ Shen HR; Li ZD; Zhong MK (November 2005). "[Preparation and evaluation of self-microemulsifying drug delivery systems containing atorvastatin]". Yao Xue Xue Bao (in Chinese). 40 (11): 982–7. PMID 16499080.
  45. ↑ Shen HR; Li ZD; Zhong MK (January 2006). "HPLC assay and pharmacokinetic study of atorvastatin in beagle dogs after oral administration of atorvastatin self-microemulsifying drug delivery system". Pharmazie. 61 (1): 18–20. PMID 16454200.
  46. ↑ Shen H; Zhong M (September 2006). "Preparation and evaluation of self-microemulsifying drug delivery systems (SMEDDS) containing atorvastatin". J. Pharm. Pharmacol. 58 (9): 1183–91. doi:10.1211/jpp.58.9.0004. PMID 16945176.
  47. 1 2 Ito Y; Kusawake T; Prasad YV; Sugioka N; Shibata N; Takada K (July 2006). "Preparation and evaluation of oral solid heparin using emulsifier and adsorbent for in vitro and in vivo studies". Int J Pharm. 317 (2): 114–9. doi:10.1016/j.ijpharm.2006.02.056. PMID 16631328.
  48. ↑ Wei L; Sun P; Nie S; Pan W (September 2005). "Preparation and evaluation of SEDDS and SMEDDS containing carvedilol". Drug Dev Ind Pharm. 31 (8): 785–94. doi:10.1080/03639040500216428. PMID 16221613. S2CID 12794172.
  49. ↑ Heo MY; Piao ZZ; Kim TW; Cao QR; Kim A; Lee BJ (May 2005). "Effect of solubilizing and microemulsifying excipients in polyethylene glycol 6000 solid dispersion on enhanced dissolution and bioavailability of ketoconazole". Arch. Pharm. Res. 28 (5): 604–11. doi:10.1007/BF02977766. PMID 15974450.
  50. ↑ Ito Y; Kusawake T; Ishida M; Tawa R; Shibata N; Takada K (June 2005). "Oral solid gentamicin preparation using emulsifier and adsorbent". J Control Release. 105 (1–2): 23–31. doi:10.1016/j.jconrel.2005.03.017. PMID 15908031.
  51. ↑ Sha X; Yan G; Wu Y; Li J; Fang X (April 2005). "Effect of self-microemulsifying drug delivery systems containing Labrasol on tight junctions in Caco-2 cells". Eur J Pharm Sci. 24 (5): 477–86. doi:10.1016/j.ejps.2005.01.001. PMID 15784337.
  52. ↑ Li P; Ghosh A; Wagner RF; Krill S; Joshi YM; Serajuddin AT (January 2005). "Effect of combined use of nonionic surfactant on formation of oil-in-water microemulsions". Int J Pharm. 288 (1): 27–34. doi:10.1016/j.ijpharm.2004.08.024. PMID 15607255.
  53. ↑ Subramanian N; Ray S; Ghosal SK; Bhadra R; Moulik SP (December 2004). "Formulation design of self-microemulsifying drug delivery systems for improved oral bioavailability of celecoxib". Biol. Pharm. Bull. 27 (12): 1993–9. doi:10.1248/bpb.27.1993. PMID 15577219.
  54. ↑ Porter CJ; Kaukonen AM; Boyd BJ; Edwards GA; Charman WN (August 2004). "Susceptibility to lipase-mediated digestion reduces the oral bioavailability of danazol after administration as a medium-chain lipid-based microemulsion formulation" (PDF). Pharm. Res. 21 (8): 1405–12. doi:10.1023/B:PHAM.0000036914.22132.cc. PMID 15359575. S2CID 8763220.
  55. ↑ Postolache P; Petrescu O; Dorneanu V; Zanini AC (2002). "Cyclosporine bioavailability of two physically different oral formulations". Eur Rev Med Pharmacol Sci. 6 (6): 127–31. PMID 12776806.
  56. ↑ Kim HJ; Yoon KA; Hahn M; Park ES; Chi SC (May 2000). "Preparation and in vitro evaluation of self-microemulsifying drug delivery systems containing idebenone". Drug Dev Ind Pharm. 26 (5): 523–9. doi:10.1081/DDC-100101263. PMID 10789064.
  57. ↑ Gibaud, S. P.; Attivi, D. (2012). "Microemulsions for oral administration and their therapeutic applications" (PDF). Expert Opinion on Drug Delivery. 9 (8): 937–951. doi:10.1517/17425247.2012.694865. PMID 22663249.
  58. ↑ Zupančič, O; Partenhauser, A; Lam, H Th; Rohrer, J; Bernkop-Schnürch, A (2016). "Development and in vitro characterisation of an oral self-emulsifying delivery system for daptomycin". European Journal of Pharmaceutical Sciences. 81: 129–136. doi:10.1016/j.ejps.2015.10.005. PMID 26485536.
  59. ↑ Leonaviciute, G; Bernkop-Schnürch, A (2015). "Self-emulsifying drug delivery systems in oral (poly)peptide drug delivery". Expert Opin Drug Deliv. 12 (11): 1703–1716. doi:10.1517/17425247.2015.1068287. PMID 26477549.
  60. ↑ Friedl, H; Dünnhaupt, S; Hintzen, F; Waldner, C; Parikh, S; Pearson, JP; Wilcox, MD; Bernkop-Schnürch, A (2013). "Development and evaluation of a novel mucus diffusion test system approved by self-nanoemulsifying drug delivery systems". J Pharm Sci. 102 (12): 4406–4413. doi:10.1002/jps.23757. PMID 24258284.
  61. ↑ Sha, X; Yan, G; Wu, Y; Li, J; Fang, X (2005). "Effect of self-microemulsifying drug delivery systems containing Labrasol on tight junctions in Caco-2 cells". Eur J Pharm Sci. 24 (5): 477–486. doi:10.1016/j.ejps.2005.01.001. PMID 15784337.
  62. ↑ Hintzen, F; Perera, G; Hauptstein, S; Müller, C; Laffleur, F; Bernkop-Schnürch, A (2014). "In vivo evaluation of an oral self-microemulsifying drug delivery system (SMEDDS) for leuprorelin". Int J Pharm. 472 (1–2): 20–26. doi:10.1016/j.ijpharm.2014.05.047. PMID 24879935.

Further reading

  • Singh, A.; Singh, V.; Juyal, D.; Rawat, G. (2015). "Self emulsifying systems: A review". Asian Journal of Pharmaceutics. 9 (1): 13. doi:10.4103/0973-8398.150031. Archived from the original on 2015-02-19. Retrieved 2015-02-19.
  • Cherniakov, I.; Domb, A. J.; Hoffman, A. (2015). "Self-nano-emulsifying drug delivery systems: an update of the biopharmaceutical aspects". Expert Opinion on Drug Delivery. 12 (7): 1121–1133. doi:10.1517/17425247.2015.999038. PMID 25556987.
  • Weerapol, Y.; Limmatvapirat, S.; Takeuchi, H.; Sriamornsak, P. (2015). "Fabrication of spontaneous emulsifying powders for improved dissolution of poorly water-soluble drugs". Powder Technology. 271: 100–108. doi:10.1016/j.powtec.2014.10.037.
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