The aim of this study was to prepare a nasal gel of risperidone and to investigate the pharmacokinetics and relative bioavailability of the drug in rats. Compared with oral dosing, the risperidone nasal gel exhibited very fast absorption and high bioavailability. Maximal plasma concentration (cmax) and the time to reach cmax (tmax) were 15.2 μg mL-1 and 5 min for the nasal gel, 3.6 μg mL-1 and 30 min for the oral drug suspension, respectively. Pharmacokinetic parameters such as tmax′, cmax and AUC of oral and nasal routes were significantly different (p < 0.01). Relative bioavailability of the drug nasal preparation to the oral suspension was up to 1600.0 %. Further, the in vitro effect of the risperidone nasal gel on nasal mucociliary movement was also investigated using a toad palate model. The risperidone nasal formulation showed mild ciliotoxicity, but the adverse effect was temporary and reversible.
1. T. Cabaleiro, D. Ochoa, R. López-Rodríguez, M. Román, J. Novalbos, C. Ayuso and F. Abad-Santos, Effect of polymorphisms on the pharmacokinetics, pharmacodynamics, and safety of risperidone in healthy volunteers, Hum. Psychopharmacol. 29 (2014) 459-469; DOI: 10.1002/hup.2420.
2. J. L. Sun, Q. X. Chen, S. Tian, F. R. Meng, Y. Lv and G. H. Du, Absorption of risperidone polymorphs administrated orally in rats, Chin. Pharm. J. 46 (2011) 1919-1922.
3. T. K. Vyas, A. Shahiwala, S. Marathe and A. Misra, Intranasal drug delivery for brain targeting, Curr. Drug Deliv. 2 (2005) 165-175; DOI: 10.2174/1567201053586047.
4. C. R. Behl, H. K. Pimplaskar, A. P. Sileno, J. deMeireles and V. D. Romeo, Effects of physicochemical properties and other factors on systemic nasal drug delivery, Adv. Drug Deliv. Rev. 29 (1998) 89-116; DOI: doi:
5. M. Kumar, A. Misra, A. K. Babbar, A. K. Mishra, P. Mishra and K. Pathak, Intranasal nanoemulsion based brain targeting drug delivery system of risperidone, Int. J. Pharm. 358 (2008) 285-291; DOI: 10.1016/j.ijpharm.2008.03.029.
6. W. N. Ma and F. G. Gu, Effect of pH on the chemical stability, solubility and oil-water partition coefficient of risperidone, Centr. South Pharm. 13 (2015) 473-476; DOI: 10.7539/j.issn.1672-2981.2015.05.006.
7. H. S. Mahajan, S. K. Shah and S. J. Surana, Nasal in situ gel containing hydroxy propyl β-cyclodextrin inclusion complex of arthemeter: development and in vitro evaluation, J. Incl. Phenom. Macrocycl. Chem. 70 (2011) 49-58; DOI: 10.1007/s10847-010-9861-x.
8. C. Tas, C. K. Ozkan, A. Savaser, Y. Ozkan, U. Tasdemir and H. Altunay, Nasal absorption of metoclopramide from different Carbopol 981 based formulations: In vitro, ex vivo and in vivo evaluation, Eur. J. Pharm. Biopharm. 64 (2006) 246-254; DOI: 10.1016/j.ejpb.2006.05.017.
9. F. G. Gu, F. D. Cui and Y. L. Gao, Preparation of prostaglandin E1-hydroxypropyl-β-cyclodextrin complex and its nasal delivery in rats, Int. J. Pharm. 290 (2005) 101-108; DOI: 10.1016/j. ijpharm.2004.11.021.
10. X. G. Jiang, J. B. Cui, X. L. Fang, Y. Wei and N. Z. Xi, Toxicity of drugs on nasal mucocilia and the method of its evaluation, Acta. Pharm. Sin. 30 (1995) 848-853; DOI: 10.3321/j.issn:0513-4870.1995.11.009.
11. M. Jug, I. Kos and M. Bećirević-Laćan, The pH-dependent complexation between risperidone and hydroxypropyl-β-cyclodextrin, J. Incl. Phenom. Macrocycl. Chem. 64 (2009) 163-171; DOI: 10.1007/ s10847-009-9549-2.
12. T. Yang, A. Hussain, J. Paulson, T. J. Abbruscato and F. Ahsan, Cyclodextrinsin nasal delivery of low molecular weight heparins: in vivo and in vitro studies, Pharm. Res. 21 (2004) 1127-1136; DOI: 10.1023/B:PHAM.0000032998.84488.7a.
13. E. Marttin, J. C. Vethoef and F. W. H. M. Merkus, Efficacy safety and mechanism of cyclodextrins as absorption enhancers in nasal delivery of peptide and protein drugs, J. Drug Targeting 6 (1998) 17-36; DOI: 10.3109/10611869808997878.
14. G. Rathnam, N. Narayanan and R. Ilavarasan, Carbopol-based gels for nasal delivery of progesterone, AAPS Pharm. Sci. Tech. 9 (2008) 1078-1082; DOI: 10.1208/s12249-008-9144-7.
15. F. G.. Gu, D. Hao, G. D. L. Meng, C. Z. Wu and Y. Wang, Preparation of bisoprolol fumarate nasal spray and its nasal delivery in rats, Pak. J. Pharm. Sci. 28 (2015) 2173-2178.