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AAPS PharmSciTech. 2006 March; 7(1): E49–E57.
Published online 2006 January 20. doi:  10.1208/pt070108
PMCID: PMC2750715

Preliminary brain-targeting studies on intranasal mucoadhesive microemulsions of sumatriptan


The aim of this investigation was to prepare microemulsions containing sumatriptan (ST) and sumatriptan succinate (SS) to accomplish rapid delivery of drug to the brain in acute attacks of migraine and perform comparative in vivo evaluation in rats. Sumatriptan microemulsions (SME)/sumatriptan succinate microemulsions (SSME) were prepared using titration method and characterized for drug content, globule size and size distribution, and zeta potential. Biodistribution of SME, SSME, sumatriptan solution (SSS), and marketed product (SMP) in the brain and blood of Swiss albino rats following intranasal and intravenous (IV) administrations were examined using optimized technetium-labeled (99mTc-labeled) ST formulations. The pharmacokinetic parameters, drug targeting efficiency (DTE), and direct drug transport (DTP) were derived. Gamma scintigraphy imaging of rat brain following IV and intranasal administrations were performed to ascertain the localization of drug. SME and SSME were transparent and stable with mean globule size 38±20 nm and zeta potential between −35 to −55 mV. Brain/blood uptake ratios at 0.5 hour following IV administration of SME and intranasal administrations of SME, SMME, and SSS were found to be 0.20, 0.50, 0.60, and 0.26, respectively, suggesting effective transport of drug following intranasal administration of microemulsions. Higher DTE and DTP for mucoadhesive microemulsions indicated more effective targeting following intranasal administration and best brain targeting of ST from mucoadhesive microemulsions. Rat brain scintigraphy endorsed higher uptake of ST into the brain. Studies conclusively demonstrated rapid and larger extent of transport of microemulsion of ST compared with microemulsion of SS, SMP, and SSS into the rat brain. Hence, intranasal delivery of ST microemulsion developed in this investigation can play a promising role in the treatment of acute attacks of migraine.

Keywords: intranasal, microemulsion, sumatriptan, radiolabel, brain targeting

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Selected References

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1. Humphrey PP, Feniuk W, Marriott AS, Tanner RJ, Jackson MR, Tucker ML. Preclinical studies on the anti-migraine drug, sumatriptan. Eur Neurol. 1991;31:282–290. doi: 10.1159/000116755. [PubMed] [Cross Ref]
2. Pakalnis A, Kring D, Paolicchi J. Parenteral satisfaction with sumatriptan nasal spray in childhood migraine. J Child Neurol. 2003;18:772–775. doi: 10.1177/08830738030180110401. [PubMed] [Cross Ref]
3. Villalon CM, Centurion D, Valdivia LF, de Vries P, Saxena PR. Migraine: pathophysiology, pharmacology, treatment and future trends. Curr Vasc Pharmacol. 2003;1:71–84. doi: 10.2174/1570161033386826. [PubMed] [Cross Ref]
4. Ahonen K, Hamalainen ML, Rantala H, Hoppu K. Nasal sumatriptan is effective in treatment of migraine attacks in children: a randomized trial. Neurology. 2004;62:883–887. [PubMed]
5. Fuseau E, Petricoul O, Moore KH, Barrow A, Ibbotson T. Clinical pharmacokinetics of intranasal sumatriptan. Clin Pharmacokinet. 2002;41:801–811. doi: 10.2165/00003088-200241110-00002. [PubMed] [Cross Ref]
6. Martindale PK. The Complete Drug Reference. London, UK: Pharmaceutical Press; 1999. pp. 450–452.
7. Gladstone JP, Gawel M. Newer formulations of the triptans: advances in migraine treatment. Drugs. 2003;63:2285–2305. doi: 10.2165/00003495-200363210-00002. [PubMed] [Cross Ref]
8. Chien YW. Nasal Drug Delivery and Delivery Systems. In: Chien YW, Su KSE, Chang S, editors. Nasal Systemic Drug Delivery. New York, NY: Marcel Dekker Inc; 1989. pp. 239–239.
9. Bigal ME, Bordini CA, Antoniazzi AL, Speciali JG. The triptan formulations: a critical evaluation. Arq Neuropsiquiatr. 2003;61:313–320. [PubMed]
10. Dahlof C. Clinical applications of new therapeutic deliveries in migraine. Neurology. 2003;61:S31–S34. [PubMed]
11. Illum L. Nasal drug delivery: problems, possibilities and solutions. J Control Release. 2003;87:187–198. doi: 10.1016/S0168-3659(02)00363-2. [PubMed] [Cross Ref]
12. Illum L. Transport of drugs from the nasal cavity to central nervous system. Eur J Pharm Sci. 2000;11:1–18. doi: 10.1016/S0928-0987(00)00087-7. [PubMed] [Cross Ref]
13. Logemann CD, Rankin LM. Newer Intranasal Migraine Medications. Am Fam Physician [serial online]. 2000. Available at: Accessed: June 15, 2004.
14. Behl CR, Pimplaskar HK, Sileno AP, De Meireles J, Romeo VD. Effects of physicochemical properties and other factors on systemic nasal delivery. Adv Drug Deliv Rev. 1998;29:89–116. doi: 10.1016/S0169-409X(97)00063-X. [PubMed] [Cross Ref]
15. Lawrence MJ, Rees GD. Microemulsion-based media as novel drug delivery systems. Adv Drug Deliv Rev. 2000;45:89–121. doi: 10.1016/S0169-409X(00)00103-4. [PubMed] [Cross Ref]
16. Ugwoke MI, Verbeke N, Kinget R. The biopharmaceutical aspects of nasal mucoadhesive drug delivery. J Pharm Pharmacol. 2001;53:3–21. doi: 10.1211/0022357011775145. [PubMed] [Cross Ref]
17. Sinswat P, Tengamnuay P. Enhancing effect of chitosan on nasal absorption of salmon calcitonin in rats: comparison with hydroxypropyl and dimethyl-beta-cyclodextrins. Int J Pharm. 2003;257:15–22. doi: 10.1016/S0378-5173(03)00090-5. [PubMed] [Cross Ref]
18. United States Pharmacopeia. Asian edition. Rockville, MD: United States Pharmacopoeial Convention; 2003.
19. Roland I, Piel G, Delattre L, Evrard B. Systemic characterization of oil-in-water emulsions for formulation design. Int J Pharm. 2003;263:85–94. doi: 10.1016/S0378-5173(03)00364-8. [PubMed] [Cross Ref]
20. Jha SK, Dougall P, Behari M, Ahuja GK. Interictal brain 99mTc-HMPAO SPECT study in chronic epilepsy. J Assoc Physicians India. 1998;46:438–441. [PubMed]
21. Eckelman WC. Radiolabeling with technetium-99m to study high-capacity and low-capacity biochemical systems. Eur J Nucl Med. 1995;22:249–263. doi: 10.1007/BF01081522. [PubMed] [Cross Ref]
22. Saha GB. Physics and Radiobiology of Nuclear Medicine. New York, NY: Springer-Verlag; 1993.
23. Babbar AK, Singh AK, Goel HC, Chauhan UPS, Sharma RK. Evaluation of 99mTc-labeled Photosan-3, a hematoporphyrin derivative, as a potential radiopharmaceutical for tumor scintigraphy. Nucl Med Biol. 2000;27:419–426. doi: 10.1016/S0969-8051(00)00092-5. [PubMed] [Cross Ref]
24. Koziara JM, Lockman PR, Allen DD, Mumper RJ. In situ blood-brain barrier transport of nanoparticles. Pharm Res. 2003;20:1772–1778. doi: 10.1023/B:PHAM.0000003374.58641.62. [PubMed] [Cross Ref]
25. Zhang Q, Jiang X, Jiang W, Lu W, Su L, Shi Z. Preparation of nimodipine-loaded microemulsion for intranasal delivery and evaluation of the targeting efficiency to brain. Int J Pharm. 2004;275:85–96. doi: 10.1016/j.ijpharm.2004.01.039. [PubMed] [Cross Ref]
26. Chow HS, Chen Z, Matsuura GT. Direct transport of cocaine from the nasal cavity to brain following intranasal cocaine administration in rats. J Pharm Sci. 1999;88:754–758. doi: 10.1021/js9900295. [PubMed] [Cross Ref]
27. Ueda T, Torihara Y, Tsuneyoshi N, Ikeda Y. Effect of sumatriptan on cerebral blood flow during migraine headache: measurement by sequential SPECT used 99mTc-ECD background substraction method. No To Shinkei. 2001;53:625–630. [PubMed]
28. Stein DJ, Van Heerden B, Wessels CJ, Van Kradenburg J, Warwick J, Wasserman HJ. Single photon emission computed tomography of the brain with Tc-99m HMPAO during sumatriptan challenge in obsessive-compulsive disorder: investigating the functional role of the serotonin auto-receptor. Prog Neuropsychopharmacol Biol Psychiatry. 1999;23:1079–1099. doi: 10.1016/S0278-5846(99)00051-2. [PubMed] [Cross Ref]
29. Espinosa-Jimenez M, Padilla-Weigand R, Ontiverous-Ortega A, Ramos-Tejada M, Perea-Carpio R. Interpretation of colloidal dyeing of polyester fabrics pretreated with ethyl xanthogenate in terms of zeta potential and surface free energy balance. J Colloid Interface Sci. 2003;265:227–233. doi: 10.1016/S0021-9797(03)00535-6. [PubMed] [Cross Ref]
30. Block LH. Pharmaceutical Emulsions and Microemulsions. In: Lieberman HA, Rieger MM, Banker GS, eds. Pharmaceutical Dosage Forms. 2nd ed. 2001;47–110.
31. Nash RA. Pharmaceutical Suspensions. In: Lieberman HA, Rieger MM, Banker GS, eds. Pharmaceutical Dosage Forms. 2nd ed. 2001;1–47.
32. Fuseau E, Petricoul O, Moore KH, Barrow A, Ibbotson T. Clinical pharmacokinetics of intranasal sumatriptan. Clin Pharmacokinet. 2002;41:801–811. doi: 10.2165/00003088-200241110-00002. [PubMed] [Cross Ref]
33. Li L, Nandi I, Kim KH. Development of an ethyl laurate-based microemulsion for rapid-onset intranasal delivery of diazepam. Int J Pharm. 2002;237:77–85. doi: 10.1016/S0378-5173(02)00029-7. [PubMed] [Cross Ref]
34. Vyas TK, Shahiwala A, Marathe S, Misra A. Intranasal drug delivery for brain targeting. Curr Drug Deliv. 2005;2:165–175. doi: 10.2174/1567201053586047. [PubMed] [Cross Ref]
35. Sakane T, Yamashita S, Yata N, Sezaki H. Transnasal delivery of 5-fluorouracil to the brain in the rat. J Drug Target. 1999;7:233–240. doi: 10.3109/10611869909085506. [PubMed] [Cross Ref]

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