Fabrication and optimization of buccal film comprising rizatriptan benzoate loaded solid lipid nanoparticles for improved ex vivo permeation

  • Pramod Salve Nanotechnology Laboratory, University Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur-440033, Maharashtra, India
  • Nikhil Bali University Department of Pharmaceutical Sciences, R.T.M. Nagpur University, Nagpur (M.S.)


The objective of the present study was to fabricate and optimize mucoadhesive buccal film encloses rizatriptan benzoate (RBZ) loaded solid lipid nanoparticles (SLNs) for improved ex-vivo permeation. RBZ loaded SLNs were formulated by hot high pressure homogenization method. SLNs were characterized for size, zeta potential and scanning electron microscopy (SEM). The RBZ SLNs comprising mucoadhesive buccal film were fabricated using dependent variables in different concentration of Eudragit RS100 and HPMC K4M by using solvent evaporation method. The formulations were experimentally optimized using two factors, three level statistical design approach. The formulated buccal film comprising RBZ SLNs evaluated for mucoadhesive strength, swelling index, drug release and ex vivo permeation. The optimized formulation of RBZ SLNs showed particle size, polydispersity index, zeta potential and entrapment efficiency i.e. 228 nm, 0.22±0.02, -14mV, 81.78% respectively. Optimized mucoadhesive buccal film formulation followed Korsmeyer-Peppas drug release kinetic model with non-Fickian diffusion mechanism. Flux, lag time, permeability values in ex vivo permeation of RBZ from SLNs loaded film were found to be 0.071µg/cm2.h, 60 min., 0.014 respectively. The flux and permeability values were increased and lag time for permeation was decreased in ex vivo permeation studies of RBZ SLNs buccal film as compared to RBZ film. The results of the in vitro and ex vivo permeation study advocate the mucoadhesive film comprising RBZ SLNs is encouraging approach for drug delivery to brain targeting diseases.

Keywords: Solid Lipid nanoparticles; Rizatriptan benzoate; Buccal film; Bioavailability.


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Author Biographies

Pramod Salve, Nanotechnology Laboratory, University Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur-440033, Maharashtra, India

Nanotechnology Laboratory, University Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur-440033, Maharashtra, India

Nikhil Bali, University Department of Pharmaceutical Sciences, R.T.M. Nagpur University, Nagpur (M.S.)

Nanotechnology Laboratory, University Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur-440033, Maharashtra, India


[1] Youns, M., Hoheise, JD., Efferth, T.: Therapeutic and diagnostic applications of nanoparticles. Curr. Drug. Targets. 12(3), 357-65 (2011)
[2] Petkar, K.C., Chavhan, S.S., Agatonovik-Kustrin, S., Sawant. K.: Nanostructured materials in drug and gene delivery are view of the state of the art. Crit. Rev. Ther. Drug. Carrier. Syst. 28(2), 101-64 (2011)
[3] Kaur, I.P., Bhandari, R., Bhandari, S., Kakkar, V.: Potential of solid lipid nanoparticles in brain targeting. J. Control. Release. 127(2), 97-109 (2008)
[4] Pardeshi, C., Rajput, P., Belgamwar, V., Tekade, A., Patil, G., Chaudhary, K., Sonje, A.: Solid lipid based nanocarriers: An overview. Acta. Pharm. 62(4), 433-7 (2012)
[5] Mishra, B., Patel, B.B., Tiwari, S.: Colloidal nanocarriers: a review on formulation technology, types and applications toward targeted drug delivery. Nanomedicine: Nanotechnology, Biology and Medicine. 6(1): 9-24 (2010)
[6] Peroutka, S.J. Migraine: A chronic sympathetic nervous system disorder. Headache the Journal of Head and Face Pain. 44(1), 53-64 (2004)
[7] Hauge, A.W., Asghar, M.S., Schytz, H.W., Christensen, K., Olesen, J.: Effects of tonabersat on migraine with aura: a randomised, double-blind, placebo-controlled crossover study. Lancet. Neurol. 8(8),718-723 (2009)
[8] Kristoffersen, E.S., Lundqvist, C.: Medication-overuse headache: epidemiology, diagnosis and treatment. Ther. Adv. Drug. Saf. 5(2), 87-99 (2014)
[9] Hamman, J.H., Enslin, G.M., Kotze, A.F.: Oral delivery of peptide drugs: barriers and developments. BioDrugs. 19(3), 165-177 (2005)
[10] Shaji, J., Patole, V.: Protein and peptide drug delivery: oral approaches. Indian. J. Pharm. Sci. 70(3), 269-277 (2008)
[11] Harris, D., Robinson, J.R.: Drug delivery via the mucous membranes of the oral cavity. J. Pharm. Sci. 81(1), 1-10 (1992)
[12] Shidhaye, S.S., Saindane, N.S., Sutar, S., Kadam, V.: Mucoadhesive bilayered patches for administration of sumatriptan succinate. AAPS. PharmSciTech. 9(3), 909-916 (2008)
[13] Rana, P., Murthy, R.S.: Formulation and evaluation of mucoadhesive buccal films impregnated with carvedilol nanosuspension: a potential approach for delivery of drugs having high first-pass metabolism. Drug. Deliv. 20(5), 224-235 (2013)
[14] Abruzzo, A., Federica, B., Teresa, C., Federica, C., Beatrice, V., Barbara, L.: Mucoadhesive chitosan/gelatin films for buccal delivery of propranolol hydrochloride. Carbohydrate Polymers. 87(1), 581-588 (2012)
[15] Keny, R.V., Desouza, C., Lourenco, C.F.: Formulation and evaluation of rizatriptan benzoate mouth disintegration tablet. Indian. J. Pharm. Sci. 72(1), 79-85 (2010)
[16] Girotra, P., Singh. S.K.: Multivariate optimization of rizatriptan benzoate-loaded solid lipid nanoparticles for brain targeting and migraine management. AAPS PharmSciTech. 18(2), 517-528 (2017)
[17] Salehi, S., Boddohi, S.: New formulation and approach for mucoadhesive buccal film of rizatriptan benzoate. Prog. Biomater. 6(4): 175-187 (2017)
[18] Rarokar, N.R., Saoji, S.D., Khedekar, P.B.: Investigation of effectiveness of some extensively used polymers on thermoreversible properties of Pluronic® tri-block copolymers. J. Drug. Dev. Sci. Tech. 44, 220-230 (2018)
[19] Rarokar, N.R., Saoji, S.D., Raut N.A., Taksande, J.B., Khedekar, P.B., Dave. V.S.: Nanostructured cubosomes in a thermoresponsive depot system: an alternative approach for the controlled delivery of docetaxel. AAPS. Pharm. SciTech. 17(2), 436-445 (2015)
[20] Mendes, A.I, Silva, A.C., Catita, J.M., Cerqueira, F., Gabriel, C., Lope, C.M.: Miconazole-loaded nanostructured lipid carriers (NLC) for local delivery to the oral mucosa: Improving antifungal activity. Colloids. Surf. B. Biointerfaces.111,755-763 (2013)
[21] Blasi, P., Schoubben, A., Traina, G., Manfroni, G., Barberini, L., Alberti, P.F., Cirotto, C., Ricci, M.: Lipid nanoparticles for brain targeting III. Long-term stability and in-vivo toxicity. Int. J. Phar. 454(1), 316-323 (2013)
[22] Shegokar, R., Singh, K.K., Müller, R.H.: Production & stability of stavudine solid lipid nanoparticles-from lab to industrial scale. Int. J. Pharm. 416(2), 461-470 (2011)
[23] Wissing, S.A., Muller, R.H., Manthei, L., Mayer, C.: Structural characterization of Q10-loaded solid lipid nanoparticles. Pharm. Res. 21(3), 400-405 (2004)
[24] Asasutjarit, R., Lorenzen, S.I., Sirivichayakul, S., Ruxrungtham, K., Ruktanonchai, U., Ritthidej, G.C.: Effect of solid lipid nanoparticles formulation compositions on their size, zeta potential and potential for In Vitro pHIS-HIV-Hugag transfection. Pharm. Res. 24(6), 1098-1107 (2007)
[25] Barman, R.K., Iwao, Y., Funakoshi, Y., Ranneh, A.H., Noguchi, S., Wahed, M.I., Itai, S.: Development of highly stable nifedipine solid–lipid nanoparticles. Chem. Pharm. Bull. 62(5), 399-406 (2014)
[26] Bhalekar, M., Upadhaya, P., Madgulkar, A.: Formulation and characterization of solid lipid nanoparticles for an anti-retroviral drug darunavir. Applied. Nanoscience. 7(1-2), 47-57 (2017)
[27] Sharma, G., Jasuja, N.D., Kumar, M., Ali. M.I.: Biological synthesis of silver nanoparticles by
cell-free extract of spirulina plantesis. J. Nanotech. 1-6 (2015)
[28] Adhikari, S.N.R., Nayak, B.S., Nayak, A.K., Mohanty, B.: Formulation and evaluation of buccal films for delivery of atenolol. AAPS. PharmSciTech. 11(3), 1038-1044 (2010)
[29] Verma, N., Wahi, A.K., Verma, A., Chattopadhayay, P.: Evaluation of a mucoadhesive buccal patch for delivery of atenolol: in vitro screening of bioadhesion. J. Pure. Appl. Microbiol. 1(1), 115-18 (2007)
[30] Nafee, N.A., Boraie, M.A., Ismail, F.A., Mortada, L.M.: Design and characterization of mucoadhesive buccal patches containing cetylpyridinium chloride (CPC). Acta. Pharma. 53(3), 199-212 (2003)
[31] Semalty, A., Semalty, M., Nautiyal, U.: Formulation and evaluation of mucoadhesive buccal films of enalapril maleate. Indian. J. Pharm. Sci. 72(5), 571-575 (2010)
[32] Patel, V.M., Prajapati. B.G., Patel. M.M.: Design and characterization of chitosan-containing mucoadhesive buccal films of propranolol hydrochloride. Acta Pharm. 57(1), 61-72 (2007)
[33] Perioli, L., Ambrogi, V., Angelici, F., Ricci. M., Giovagnoli. S., Capuccella. M., Rossi, C.: Development of mucoadhesive patches for buccal administration of ibuprofen. J. Control. Release. 99(1), 73-82 (2004)
[34] Dalvi, S.V., Dave, R.N.: Controlling particle size of a poorly water-soluble drug using ultrasound and stabilizers in antisolvent precipitation. Ind. Eng. Chem. Res. 48(16), 7581-7593 (2009)
[35] Ostertag, F., Weiss, J., McClements, D.J.: Low-energy formation of edible nanoemulsions:factors influencing droplet size produced by emulsion phase inversion. J. Colloid. Interface. Sci. 388(1), 95-102 (2012)
[36] Upadhyay, S., Pate, J., Patel, V., Saluja, A.: Effect of different lipids and surfactants on formulation of solid lipid nanoparticles incorporating tamoxifen citrate. J. Pharm. Bioallied. Sci. 4(Suppl 1), S112-S113 (2012)
[37] Kraisit, P., Limmatvapirat, S., Nunthanid, J., Sriyamornsak, P., Luangtana-Anan M.: Preparation and characterization of hydroxypropyl methylcellulose/polycarbophil mucoadhesive blend films using a mixture design approach. Chem. Pharm. Bull. 65(3), 284-294 (2017)
[38] Garg, S., Kumar, G.: Development and evaluation of a buccal bioadhesive system for smoking cessation therapy. Pharmazie. 62(4), 266-272 (2007)
[39] Kundu, J., Patra, C., Kundu, S.C.: Design, fabrication and characterization of silk fibroin HPMC-PEG blended films as vehicle for transmucosal delivery. Mater. Sci. Eng. C. 28(8), 1376-1380 (2008)
[40] Giovino, C., Ayensu, I., Tetteh, J.: An integrated buccal delivery system combining chitosan films impregnated with peptide loaded PEG-b-PLA nanoparticles. Colloids. Surf. B. Biointerfaces. 112, 9-15 (2013)
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How to Cite
Salve P, Bali N. Fabrication and optimization of buccal film comprising rizatriptan benzoate loaded solid lipid nanoparticles for improved ex vivo permeation. JDDT [Internet]. 15Jun.2019 [cited 24Jan.2021];9(3-s):636-48. Available from: http://jddtonline.info/index.php/jddt/article/view/3112