• SARASWATHI T. S. Department of Pharmaceutics, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India
  • MOTHILAL M. Department of Pharmaceutics, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India



Niosomes, Blood-brain barrier, Factorial design, In situ gel, Rivastigmine, Intranasal


Objective: Aim of the study is to develop rivastigmine-loaded niosomal in situ gel via the intranasal route to the brain by crossing the Blood-Brain Barrier. For the treatment of Alzheimer’s disease, it provides a speedy onset of action, a faster therapeutic effect, avoidance of the first-pass metabolism, and enhanced bioavailability.

Methods: Rivastigmine niosomal in situ nasal gel was developed, refined and tested with the goal of delivering the medicine to the brain via the intranasal route Rivastigmine niosomes were formulated by thin-film hydration technique, optimized using (32) factorial design and characterized for its physicochemical parameters. Rivastigmine-loaded niosomes were further incorporated into Carbopal-934P and HPMC-K4M liquid gelling system to form in situ nasal gel. The resulting solution was evaluated for several parameters including, viscosity at pH 5 and pH 6, gelling capacity and gelling time.

Results: Optimized best formulation containing span 60 (A) and cholesterol (B) with (1:0.5) ratio identified from the model developed from Design-Expert®12 software, exhibited Entrapment efficiency (76.5±0.23%), particle size (933.4±0.14 nm), in vitro drug release maximum (68.94±0.26%) at 8th hour and further studied for its characteristics by SEM and TEM showed stable vesicles. Polynomial equations of Y1, Y2, and Y3 were conducted and ANOVA results showed a significant impact (p<0.05) on three levels. In vivo perfusion studies using rat model showed, the niosomes developed has good perfusion compared to pure drug with 27.2% of drug absorption in the brain at the end of 3 h. In vitro permeation of Rivastigmine through the dialysis membrane showed that 60.74% w/w drug permeated after 8 h. The formation of stable vesicles was proved by Zeta potential measurements and SEM analysis.

Conclusion: Optimized formulation had greater perfusion and was expected to have a good bioavailability compared to conventional other drug delivery systems.


Download data is not yet available.


Squire LR, Zola-Morgan S. The medial temporal lobe memory system. Science 1991; 253:1380-6.

Cummings JL, Cole G. Alzheimer disease. JAMA 2002;287:2335-38.

Hussain AA. Intranasal drug delivery. Adv Drug Deliv Rev 1998;29:39-4.

Barakat NS, Omar SA, Ahmed AAE. Carbamazepine uptake into rat brain following intra-olfactory transport. J Pharm Pharmacol 2005;58:63–72.

Dahlin M, Bergman U, Jansson B, Bjork E, Brittebo E. Transfer of dopamine in the olfactory pathway following nasal administration in mice. Pharm. Res 2000;17:737-742.

Henriksson J, Tjalve H. Uptake of inorganic mercury in the olfactory bulbs via olfactory pathways in rats. Environ Res 1998;77:130-40.

Chou KJ, Donovan MD. Lidocaine distribution into the CNS following nasal and arterial delivery: a comparision of local sampling and microdialysis techniques. Int J Pharm 1998;171:53-61.

Eriksson C, Bergman U, Franzen A, Sjoblom M, Brittebo EB. Transfer of some carboxylic acids in the olfactory system following intranasal administration. J. Drug Target 1997;7:131-42.

Prey WH, Liu J, Chen X, Thorne RG, Fawcett JR, Ala TA, et al. Delivery of 125I-NGF to the brain via the olfactory route. Drug Deliv 1997;4:87-92.

Thorne RG, Emory CR, Ala TA, Frey WH. Quantitative analysis of the olfactory pathway for drug delivery to the brain. Brain Res 1995;692:278-82.

Illum L. Transport of drugs from the nasal cavity to the central nervous system. Eur J Pharm Sci 2000;11-18.

Polinsky RJ, Clinical pharmacology of rivastigmine: A new generation acetyl choline esterase inhibitor for the treatment of Alzheimer’s disease. Clin Ther 1998;20:634-37.

Subodh D, Amit J, Mehta SC, Pavan G, Sandeep J, Jagdish S. Niosomes: The ultimate drug carrier. Drug Inven Today 2010;2:72-77.

Uchegbu FI, Vyas PS. Non-ionic surfactant based vesicles (niosomes) in drug delivery. Int J Pharm 1998;33:172.

Rajalakshmi SV, Vinaya OG. Formulation Development, Evaluation and optimization of medicated Lip Rouge containing niosomal Acyclovir for the management of recurrent Herpes Labialis. Int J Appl Pharm Sci 2017; 9:21-27.

Lavanya B, Indira S, Srinivas P. Formulation and Evaluation of Ocular Niosomal In situ gels of Linezolid. Int J Pharm Sci Res 2014;5:1367-75.

Astrid permatasari isnan, Mahdi jufri. Formulation of niosomal gel containing green tea extract (camellia sinensis l. kuntze) using thin-layer hydration. Int J app Pharm 2017; 9 Suppl 1:38-43.

Sathali AAH, Rajalakshmi G. Evaluation of transdermal targeted niosomal drug delivery of terbinafine hydrochloride. Int J PharmTech Res 2010; 2:2081–89.

GayathriDevi S, Venkatesh, Udupa N. Niosomal sumatriptan succinate for nasal administration. Int. J. Pharm. Sci 2010;480-81.

Hussain A, Dittert LW, Traboulsi A. Brain delivery of folic acid for the prevention of of Alzheimer’s disease and stroke. US Patent 6369058B1; 2002.

Song J, Bi H, Xie X, Guo J, Wang X, Liu D. Preparation and evaluation of sinomenine hydrochloride in situ gel for uveitis treatment. Int Immunopharmacol 2013;17:99-107.

Cai Z, Song X, Sun F, Yang Z, Hou S, Liu Z. Formulation and evaluation of in situ gelling systems for intranasal administration of gastrodin. AAPS Pharm Sci Tech 2011; 12:1102-9.

Mahajan H, Dinger S. Design and invitro evaluation of nanoemulsion for nasal delivery of artemether. Ind J Nov Drug Deliv 2011;3:272-7.

Uchegbu IF, Double JA, Kelland LR, Turton JA, Florence AT. The activity of doxorubicin niosomes against an ovarian cancer cell line and three invivo mouse tumour models. J Drug Target 1996;3:399-409.

Dahiya NK, Rao R, Nanda S. Preparation and characterization techniques in the niosomal vesicular systems-a review. J Pharm Biomed Sci 2011;5:1-8.

Tank Chintankumar J, Borkhataria Chetan H, Baria Ashok H, Patel Rakesh P, Tamizharasi S, Dipen K, et al. Formulation and evaluation of aceclofenac Loaded maltodextrin based proniosome, Int J Chem Tech Res 2009;1:567-73.

Girigoswami A, Das S, De S. Fluorescence and dynamic light scattering studies of niosomes-membrane mimetic systems. Spectrochim Acta A Mol Biomol Spectrosc 2006;64:859-66.

Kamel R, Basha M, Abdel-Alim SH. Development of a novel vesicular system using a binary mixture of sorbitan monostearate and polyethylene glycol fatty acid esters for rectal delivery of rutin. J Lip Res 2013;23:28-36.

Guinedi AS, Mortada ND, Mansour S, Hathout RM. Preparation and evaluation of reverse-phase evaporation and multilamellar niosomes as ophthalmic carriers of acetazolamide. Int J Pharm 2005;306:71-82.

Rhodes D. Maltodextrin-based proniosomes. AAPS Pharm Sci 2001;3:1-8.

Semple, Sean C. Arcadio Chonn, Pieter R. Cullis, Influence of Cholesterol on the Association of Plasma Proteins with Liposomes. Biochem 1996;35:2521-25.

Kenneth J. Reversible gel forming composition for sustained delivery of bio-affecting substances, and methods of use. US Patent 5599534 A;1997.

Dakhara Sanjay L, Anajwala Chetan C, Singhal Nirav A, Selote Vidula S. Phospholipids and non-ionic surfactants containing niosome is far better than liposome as ophthalmic dosage form. J Pharm Res 2010;3:2488-91.

Thomas L, Viswanad V. Formulation and optimization of clotrimazole-loaded proniosomal gel using 3(2) factorial design. Sci Pharm 2012;80:731-48.

Anjan D, Subrata C, Arup M, Jayanta C. Formulation and Development of In situ Gelling System for Nasal Administration for Ondansetron Hydrochloride by Using Pluronic F-127. J Pharm Pharma Sci 2013;2:52-61.

Srinivas S, Kumar YA, Hemanth A, Anitha M. Preparation and evaluation of niosomes containing Aceclofenac. DJNB 2010;5:249-54.

Abdelbary GA, Aburahma MH. Oro-dental mucoadhesive proniosomal gel formulation loaded with lornoxicam for management of dental pain. J Liposome Res 2015;25:107-21.

Jain SP, Shah SP, Rajadhyaksha NS, Singh P S PP, Amin PD. Insitu ophthalmic gel of ciprofloxacin hydrochloride for once a day sustained delivery. Drug Dev Ind Pharm 2008;34:445-52.

Ravouru N, Kondreddy P, Korakanchi D, Haritha M. Formulation and evaluation of niosomal nasal drug delivery system of folic acid for brain targeting. Curr Drug Discov Technol;2013:10:270-82.

Shirsand SB, Para MS, Nagendrakumar D, Kanani KM, Keerthy D. Formulation and evaluation of Ketaconazole niosomal gel drug delivery system, Int J Pharm Invest 2012;2:201.

Akhtar N, Arkvanshi S, Bhattacharya SS, Verma A, Pathak K. Preparation and evaluation of a buflomedil hydrochloride niosomal patch for transdermal delivery. J lip Res 2015;25:191-201.

Zhang Y, Zhang K, Wu Z, Guo T, Ye B, Lu M, et al. Evaluation of transdermal salidoside delivery using niosmes via invitro cellular uptake. Int J Phar 2015;478:138-46.



How to Cite




Original Article(s)