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Preparation and Evaluation of Tubular Micelles of Pluronic Lecithin Organogel for Transdermal Delivery of Sumatriptan

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Abstract

The present work focuses on the preparation and evaluation of lecithin organogel system of thermoreversible polymer pluronic F127, which would enhance the stability and absorption of sumatriptan succinate across the skin. Formulations were developed with and without co-surfactant (pluronic F127). The prepared organogels were evaluated for its appearance, organoleptic characteristics, and feel upon application, homogeneity, occlusivenes, washability, pH, viscosity, spreadability, gel transition temperature of formulations. The formulations were also evaluated for drug content, in vitro drug diffusion properties and skin irritation testing. In vivo evaluation of formulations was carried out by hot plate and writhing test method, and finally the optimized formulation was subjected to stability studies. The developed formulations were easily washable, smooth in feel, and showed no clogging which indicate superior texture of system. Formulation, containing pluronic showed greater spreadability and higher drug diffusion rate as compared to pluronic free organogel. Drug content of organogel formulations was in the range of 94–97%. The pH of the formulations was 6.48 ± 0.5 and 6.98 ± 0.1, reflecting no risk of skin irritation. Pluronic not only enhances the stability of organogel by increasing the viscosity (from 6,541 ± 234.76 to 7,826 ± 155.65 poise) but also increases the release of drug from 67.39 ± 1.53% to 74.21 ± 1.7%. The sumatriptan exhibits higher and long lasting antinociceptive effect as indicated by the persistent increase in reaction time in hot plate and inhibited abdominal contraction in acetic acid-induced writhing test (p < 0.05). The prepared optimized formulation was found to be stable without any significant changes at room temperature.

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REFERENCES

  1. Hermans PH. Gels. In: Kruyt HR, editor. Colloid science (volume 2). Amsterdam, The Nederlands: Elsevier; 1949. p. 483–651.

    Google Scholar 

  2. Flory PJ. Introductory lecture. Disc Faraday Soc. 1974;57:7–18.

    Article  CAS  Google Scholar 

  3. Almdal K. Towards a phenomenological definition of the term gel. Polym Gels Netw. 1993;1:5–17.

    Article  CAS  Google Scholar 

  4. Abdallah DJ, Lu L, Weiss RG. Thermoreversible organogels from alkane gelators with one heteroatom. Chem Mater. 1999;11:2907–11.

    Article  CAS  Google Scholar 

  5. Abdallah DJ, Weiss RG. n-Alkanes gel n-alkanes (an many other organic liquids). Langmuir. 2000;16:352–5.

    Article  CAS  Google Scholar 

  6. Capitani D, Segre AL, Dreher F, Walde P, Luisi PL. Multinuclear NMR investigation of phosphatidylcholine organogels. J Phys Chem. 1996;100:15211Y15217.

    Article  Google Scholar 

  7. Walde P, Giuliani AM, Boicelli CA, Luisi PL. Phospholipid-based reverse micelles. Chem Phys Lipids. 1990;53:265Y288.

    Article  Google Scholar 

  8. Shumilina EV, Khromova Y, Shchipunov YA. A study of the structure of lecithin organic gels by Fourier-transform IR spectroscopy. Zh Fiz Khim. 2000;74:1210Y1219.

    Google Scholar 

  9. Shchipunov YA, Duressschmidt T, Hoffmann H. Electrorheological effects in lecithin organogels with water and glycerol. J Colloid Interface Sci. 1990;212:390–401.

    Article  Google Scholar 

  10. Shchipunov YA. Lecithin organogel: a micellar system with unique properties. Colloids surf A Physicochem Eng Asp. 2001;183–185:541–54.

    Article  Google Scholar 

  11. Shchipunov YA. Lecithin organogel: rheological properties of polymer-like micelles formed in the presence of water. Colloid J. 1995;57:556–60.

    CAS  Google Scholar 

  12. Shchipunov YA, Duressschmidt T, Hoffmann H. End to end fusion of polymer-like micelles in the lecithin organogel under the action of an electric field. Langmuir. 2000;16:297–9.

    Article  CAS  Google Scholar 

  13. Shchipunov YA, Shumilina EV. Lecithin bridging by hydrogen bonds in the organogel. Mater Sci Eng C. 1995;3 Suppl 1:43.

    Article  Google Scholar 

  14. Shchipunov YA, Shumilina EV. Molecular model for the lecithin self-organization into polymer-like micelles. Prog Colloid Polym Sci. 1997;106 Suppl 1:228.

    Article  Google Scholar 

  15. Wessman M, Gisela M. Migraine: a complex genetic disorder. Lancet Neurol. 2007;6:521–32.

    Article  CAS  PubMed  Google Scholar 

  16. The Headache Classification Committee of the International Headache Society. The international classification of headache disorders: 2nd edition. Cephalalgia. 2004;24 Suppl 1:160.

    Google Scholar 

  17. Villalon CM, Centurion D, Valdivia LF, De Varis P, Saxena PR. Migraine: pathophysiology, pharmacology treatment and future trends. Curr Vasc Pharmacol. 2003;1:71–84.

    Article  CAS  PubMed  Google Scholar 

  18. Humphrey PP, Feniuk W, Marriott AS, Tanner RJ, Jackson MR, Tucker ML. Preclinical studies on antimigrine drugs. Eur Neurol. 1991;31:282–90.

    Article  CAS  PubMed  Google Scholar 

  19. Jhee SS, Shiovitz T, Crawford AW, Cutler NR. Pharmacokinetics and pharmacodynamics of the triptan antimigraine agents: a comparative review. Clin Pharmacokinet. 2001;40:189–205.

    Article  CAS  PubMed  Google Scholar 

  20. Upadhyay KK, Tiwari C, Khopade AJ, Bohidar HB, Jain SK. Sorbitan Ester organogels for transdermal delivery of sumatriptan. Drug Dev Ind Pharm. 2007;33:617–25.

    Article  CAS  PubMed  Google Scholar 

  21. Goadsby PJ, Lipton RB, Ferrari MD. Migraine: current understanding and treatment. N Engl J Med. 2002;346:257–70.

    Article  CAS  PubMed  Google Scholar 

  22. Aurora SK, Kori SH, Barrodale P, McDonald SA, Haseley D. Gastric stasis in migraine: more than just a paroxysmal abnormality during a migraine attack. Headache. 2006;46:57–63.

    Article  PubMed  Google Scholar 

  23. Pierce M, Marbury T, Neill CO, Siegel S, Du W, Sebree T. Zelrix™: a novel transdermal formulation of sumatriptan. Headache. 2009;49:817–25.

    Article  PubMed  Google Scholar 

  24. Siegel SJ, Neill CO, Dube LM, Kaldeway P, Morris R, Jackson D, et al. Aunique iontophoretic patch for optimal transdermal delivery of sumatriptan. Pharm Res. 2007;24:1919–26.

    Article  CAS  PubMed  Google Scholar 

  25. Bhatia A, Singh B, Amarji B, Katare OP. Tamoxifen-Loaded liposomal topical formulation arrests hair growth in mice. Br J Dermatol Nurs. 2009. doi:10.1111/j.1365-2133.2010.09880.x.

    Google Scholar 

  26. Gupta M, Goyal AK, Paliwal SR, Paliwal R, Mishra N, Vaidya B, et al. Development and characterization of effective topical liposomal system for localized treatment of cutaneous candiasis. J Liposome Res. 2010;20(4):341–50.

    Article  CAS  PubMed  Google Scholar 

  27. Dragicevic-Curic N, Winter S, Krajisnik D, Stupar M, Milic J, Graefe S, et al. Stability evaluation of temoporfin-loaded liposomal gels for topical application. J Liposome Res. 2010;20(1):38–48.

    Article  CAS  PubMed  Google Scholar 

  28. Puglia C, Filosa R, Peduto A, de Caprariis P, Rizza L, Bonina F, et al. Evaluation of alternative strategies to optimize ketorolac transdermal delivery. AAPS PharmSciTech. 2006;7(3):E1–9. doi:10.1208/pt070364. Article 64.

    Article  Google Scholar 

  29. Ferderber K, Hook S, Rades T. Phosphatidyl choline-based colloidal systems for dermal and transdermal drug delivery. J Liposome Res. 2009;19(4):267–77.

    Article  CAS  PubMed  Google Scholar 

  30. Luciana BL, Hillary VDW, Hsin TL, Vijay V, Hsin KL, Stan N, et al. Topical delivery of lycopene using microemulsions: enhanced skin penetration and tissue antioxidant activity. J Pharm Sci. 2009;99(3):1346–57.

    Google Scholar 

  31. Scalia S, Mezzena M, Iannuccelli V. Influence of solid lipid microparticle carriers on skin penetration of the sunscreen agent, 4-methylbenzylidene camphor. J Pharm Pharmacol. 2007;59:1621–7.

    Article  CAS  PubMed  Google Scholar 

  32. Jain SK, Gupta Y, Jain A, Rai K. Enhanced transdermal delivery of acyclovir sodium via elastic liposomes. Drug Deliv. 2006;15:141–7.

    Article  Google Scholar 

  33. Maestrelli F, Capasso G, González-Rodríguez ML, Antonio M, Rabasco CG, Mura P. Effect of preparation technique on the properties and in vivo efficacy of benzocaine-loaded ethosomes. J Liposome Res. 2009;19(4):253–60.

    Article  CAS  PubMed  Google Scholar 

  34. Bendas ER, Tadros MI. Enhanced Transdermal Delivery of Salbutamol Sulfate via Ethosomes. AAPS PharmSciTech 2007; 8 (4) Article 107

    Google Scholar 

  35. Bender J, Simonsson C, Smedh M, Engström S, Ericson MB. Lipid cubic phases in topical drug delivery: visualization of skin distribution using two-photon microscopy. J Control Release. 2008;129(3):163–9.

    Article  CAS  PubMed  Google Scholar 

  36. Bender J, Ericson MB, Merclin N, Iani V, Rosen A, Engstrom S, et al. Lipid cubic phases for improved topical drug delivery in photodynamic therapy. J Control Release. 2005;106:350–60.

    Article  CAS  PubMed  Google Scholar 

  37. de Jalon EG, Blanco-Prıeto MJ, Ygartua P, Santoyo S. Topical application of acyclovir-loaded microparticles: quantification of the drug in porcine skin layers. J Control Release. 2001;75:191–7.

    Article  PubMed  Google Scholar 

  38. de Jalon EG, Blanco-Prıeto MJ, Ygartua P, Santoyo S. PLGA microparticles: possible vehicles for topical drug delivery. I J Pharm. 2001;226:181–4.

    Google Scholar 

  39. Santoyo S, de Jalon EG, Ygartua P, Renedo MJ, Blanco-Prıeto MJ. Optimization of topical cidofovir penetration using microparticles. I J Pharm. 2002;242:107–13.

    CAS  Google Scholar 

  40. Amrutiya N, Bajaj A, Madan M. Development of microsponges for topical delivery of mupirocin. AAPS PharmSciTech. 2009;10(2):402–9.

    Article  CAS  PubMed  Google Scholar 

  41. Haddadi A, Aboofazeli R, Erfan M, Farboud ES. Topical delivery of urea encapsulated in biodegradable PLGA microparticles: O/W and W/O creams. J Microencapsul. 2008;25(6):379–86.

    Article  CAS  PubMed  Google Scholar 

  42. Shim J, Kang HS, Won-Seok P, Sang-Hun H, Kim J, Ih-Seop C. Transdermal delivery of mixnoxidil with block copolymer nanoparticles. J Control Release. 2004;97:477–84.

    CAS  PubMed  Google Scholar 

  43. Alvarez-Roman R, Naik A, Kalia YN, Guy RH, Fessi H. Enhancement of topical delivery from biodegradable nanoparticles. Pharm Res. 2004;21(10):1818–25.

    Article  CAS  PubMed  Google Scholar 

  44. Rancan F, Papakostas D, Hadam S, Hackbarth S, Delair T, Primard C, et al. Investigation of polylactic acid (PLA) nanoparticles as drug delivery systems for local dermatotherapy. Pharm Res. 2009;26(8):2027–36.

    Article  CAS  PubMed  Google Scholar 

  45. Pandey M, Belgamwar V, Gattani S, Surana S, Tekade A. Pluronic lecithin organogel as a topical drug delivery system. Drug Deliv. 2010;17(1):38–47. doi:10.3109/10717540903508961.

    Article  CAS  Google Scholar 

  46. Dhiman M, Yedurkar P, Sawant KK. Formulation, characterization, and in vitro evaluation of bioadhesive gels containing 5-fluorouracil. Pharm Dev Technol. 2008;13(1):15–25.

    Article  CAS  PubMed  Google Scholar 

  47. Naik A, Kalia YN, Guy RH. Transdermal drug delivery: overcoming the skin’s barrier function. Pharm Sci Technol Today. 2000;3:318–26.

    Article  CAS  PubMed  Google Scholar 

  48. Idson B, Lazarus J. Semisolids. In: The theory and practice of industrial pharmacy. Bombay, India: Vargehese Publishing House; 1991. p. 534–63.

    Google Scholar 

  49. Escobar-Chávez JJ, López-Cervantes M, Naïk A, Kalia YN, Quintanar-Guerrero D, Ganem-Quintanar A. Applications of thermoreversible pluronic f-127 gels in pharmaceutical formulations. J Pharm Pharmaceut Sci. 2006;9(3):339–58.

    Google Scholar 

  50. Murdan S. A review of pluronic lecithin organogel as a topical and transdermal drug delivery system. Hosp Pharm. 2005;12:267–70.

    Google Scholar 

  51. Kumar R, Katare OP. Lecithin organogels as a potential phospholipid-structured system for topical drug delivery: a review. AAPS PharmSciTech. 2005;06 Suppl 02:E298–310.

    Article  Google Scholar 

  52. Nasseri AA, Aboofazeli R, Zia H, Needham TE. Lecithin stabilized microemulsion: an organogel for topical application of ketorolac tromethamine I: phase behavior studies. Iran J Pharm Res. 2003;2:59–61.

    CAS  Google Scholar 

  53. Shchipunov YA, Shumilina EV. Lecithin organogels: role of polar solvent and nature of intermolecular interactions. Colloid J. 1996;58:117–25.

    CAS  Google Scholar 

  54. Willimann H, Walde P, Luisi PL, Gazzaniga A, Stroppolo F. Lecithin organogel as matrix for transdermal transport of drugs. J Pharm Sci. 1992;81:871–4.

    Article  CAS  PubMed  Google Scholar 

  55. Anand B. Applications of organogels in pharmaceuticals. J Sci Ind Res. 2001;60 Suppl 4:311–8.

    CAS  Google Scholar 

  56. Suh H, Jun HW. Physicochemical and release studies of naproxen in poloxamer gels. Int J Pharm. 1996;129:13–20.

    Article  CAS  Google Scholar 

  57. Ghelardini C, Galeotti N, Figini M, Imperato A, Nicolodi M, Sicuteri F, et al. The central cholinergic system has a role in the Antinociception induced in rodents by anti migraine drug sumatriptan. J Pharmacol Ther. 1996;279:884–90.

    CAS  Google Scholar 

  58. Rohit, Rao C, Krishna G. Effect of captopril and losartan on thermal and chemical induced pain in mice. Indian J Physiol Pharmacol. 2006;50 Suppl 2:169–74.

    Google Scholar 

  59. Kulkarni SK, Jain NK. Pharmacological and pharmacokinetics studies on marketed gel formulations of nimesulide. Indian Drugs. 2001;38 Suppl 2:63–6.

    Google Scholar 

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ACKNOWLEDGMENTS

The authors would like to acknowledge Aurobindo Pharmaceutical Ltd. Hyderabad (India), for providing free gift sample of sumatriptan succinate. The authors are very thankful to the management of School of Pharmaceutical Sciences, Rajiv Gandhi Technical University, for providing necessary facilities and encouragement. Authors are also thankful to Head, Department of Pharmaceutical Sciences, IPS Academy, Indore (India) for providing facilities for in vivo animal studies.

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Correspondence to Suman Ramteke.

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Agrawal, V., Gupta, V., Ramteke, S. et al. Preparation and Evaluation of Tubular Micelles of Pluronic Lecithin Organogel for Transdermal Delivery of Sumatriptan. AAPS PharmSciTech 11, 1718–1725 (2010). https://doi.org/10.1208/s12249-010-9540-7

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