Indian Journal of Pharmaceutical Sciences
Users online: 40
Scientific Publication of the Indian Pharmaceutical Association
Home Email this page Print this page Bookmark this page Decrease font size Default font size Increase font size
The Journal Search Current Issue Archives Instructions Online submission Login  


 
ABSTRACT
Year : 2009  |  Volume : 71  |  Issue : 6  |  Page : 723-725
Thermoreversible biogels for intranasal delivery of rizatriptan benzoate


Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai-400 098, India

Date of Web Publication3-Feb-2010

Correspondence Address:
Hema A Nair
Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai-400 098
India
Login to access the Email id


Get Permissions

   Abstract 

The objective of the present study was to formulate and evaluate a thermoreversible formulation containing rizatriptan benzoate for intranasal administration. Chitosan and aqueous β-glycerolphosphate were mixed in cold condition to obtain chitosan-β-glycerolphosphate mixtures, which served as the thermoreversible systems. Rizatriptan benzoate was incorporated at a final strength of 25 mg/ml. Both in vitro release and ex vivo permeation of rizatriptan from gels were measured at 37º using Franz diffusion cells Formulations were tested in vivo in mice for reduction in locomotor activity using digital actophotometer and nasal mucosal tissues were examined histopathologically.


Keywords: Thermoreversible gels, rizatriptan benzoate, chitosan


How to cite this article:
Chand R, Naik AA, Nair HA. Thermoreversible biogels for intranasal delivery of rizatriptan benzoate. Indian J Pharm Sci 2009;71:723-5

How to cite this URL:
Chand R, Naik AA, Nair HA. Thermoreversible biogels for intranasal delivery of rizatriptan benzoate. Indian J Pharm Sci [serial online] 2009 [cited 2014 Sep 1];71:723-5. Available from: http://www.ijpsonline.com/text.asp?2009/71/6/723/59568


The nasal route has been successfully exploited for systemic delivery of drugs and vaccines. This route also offers the possibility of preferential targeting of drugs to CNS via olfactory pathway, bypassing the blood brain barrier [1] . The objective of the present study was to formulate and evaluate a thermoreversible formulation containing the antimigraine drug rizatriptan benzoate (RB) for intranasal (IN) administration. The gels are based on the mucoadhesive biopolymer chitosan and utilize β−glycerolphosphate (GP) (C-GP-PEG) and without PEG (polyethylene glycol) (C-GP).


   Materials and Methods Top


Chitosan (degree of deactylation~89%) and RB were gifted by CIFT and Cipla Pvt. Ltd. respectively. GP was purchased from CDH and PEG 4000 from S. D. Fine Chem, Mumbai, India. All other reagents used in the study were of analytical grade.

Preparation of gels:

Chitosan dissolved in 0.1N HCl and aqueous GP were mixed in cold condition to obtain chitosan-GP (C-GP) mixtures, which served as the thermoreversible systems. Formulations containing PEG 1% w/v (C-GP-PEG) with lower GP content were also prepared. RB was incorporated at a final strength of 25 mg/ml.

Evaluation of Gels:

The gelling temperature and time were measured by gradually warming the sols until movement of the meniscus was arrested. Gel strength was measured at 37º in terms of time taken for a 7 g stainless steel ball to fall through 4 cm height of gel. Both in vitro release and ex vivo permeation of RB from gels into PBS (pH 6.4) were measured at 37º using Franz diffusion cells across parchment paper and sheep nasal mucosa, respectively followed by UV spectrophotometric analysis [2] . Mucoadhesive strength of the formulations in both sol and gel states were determined using a modified two-pan balance as the force required to separate two porcine mucin coated surfaces with gel between them. Formulations were tested in vivo in mice for reduction in locomotor activity using digital actophotometer and nasal mucosal tissues were examined histopathologically. Statistical analysis was performed using ANOVA followed by Bonferroni's multiple comparison test whenever applicable (P value<0.001).


   Results and Discussion Top


The formulations were fluid at room temperature and were rapidly transformed to viscous gels at 37 0 . Both gels showed initial burst followed by gradual release and permeation and release from C-GP gels were more rapid than from the gels with PEG [Figure 1] and [Figure 2]. The gels had mucoadhesion comparable to or greater than chitosan at 25 0 , but the adhesiveness was significantly reduced on gelation at 37 0 [Figure 3]. In vivo results revealed significant and sustained reduction in locomotor activity of mice on IN administration of both formulations in comparison to drug solution [Figure 4]. Histopathology revealed minor damage to nasal tissues after 5 days of exposure [Figure 5].

The weakly basic GP prevents precipitation of chitosan on increase in pH and facilitates hydrophobic interactions on slight elevation of temperature resulting in thermoreversible systems. The sols showed good mucoadhesion but gelling reduced this effect due to stronger bonding within polymeric chains rather than with mucin. The pronounced and prolonged depression in locomotor activity of mice strengthens the hypothesis of direct delivery to brain. Preliminary studies also indicate a good safety profile. In conclusion, the developed biogel formulations could prove to be promising alternative therapy with RB. The formulations offer convenience of administration and prolong nasal residence time and thereby nasal absorption of RB.


   Acknowledgements Top


CIFT, Cochin for sample of chitosan and Cipla Pvt. Ltd for rizatriptan benzoate.

 
   References Top

1.Talegaonkar S, Mishra PR. Intranasal delivery: An approach to bypass the blood brain barrier. Indian J Pharmacol 2004;36:140-7.  Back to cited text no. 1    Medknow Journal  
2.Jain SK, Jain NK, Jain A, Jain D, Gupta Y. Mucoadhesive chitosan microspheres for noninvasive and improved nasal delivery of insulin. Indian J Pharm Sci 2007;69:498-504.  Back to cited text no. 2    Medknow Journal  


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]

This article has been cited by
1 Formulation and in-vitro evaluation thermoreversible rizatriptan benzoate nasal gel
Khairnar, P.S., Walke, P.S., Narkhede, M.R., Nehete, J.Y.
International Journal of Pharmacy and Pharmaceutical Sciences. 2011; 3(4): 250-256
[Pubmed]



 

Top
Print this article  Email this article
 
  Search
   
   Next article
   Previous article 
   Table of Contents
  
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Article in PDF (1,193 KB)
    Citation Manager
    Access Statistics
    Reader Comments
    Email Alert *
    Add to My List *
* Registration required (free)  


    Abstract
    Materials and Me...
    Results and Disc...
    Acknowledgements
    References
    Article Figures

 Article Access Statistics
    Viewed1285    
    Printed49    
    Emailed0    
    PDF Downloaded187    
    Comments [Add]    
    Cited by others 1    

Recommend this journal