Formulation development and characterization of in-situ gel of Rizatriptan Benzoate for intranasal delivery
The present investigation was aimed to formulate and characterize ion-activated in-situ gel loaded with Rizatriptan Benzoate (RIZ) for intranasal administration for brain targeting. The gel was further optimized for process and formulation parameters by using 32 factorial design. The optimized batch having the concentrations of gellan gum and HPMC E15 LV 33.83 mg and 9.6 mg respectively. Gel strength and mucoadhesive strength of the optimized formulation were found to be 32.54 sec and 2580.50 dynes/cm2 respectively. Moreover, improved in-vitro and ex-vivo release profile of in-situ gel were observed in comparison to drug solution. In a nutshell, the developed formulation holds a great promise in overcoming the limitation associated with currently marketed RIZ formulations and illustrates the potential use of ion-activated in-situ gel to administer the drug by nasal route for brain targeting.
Keywords: In-situ gel, Rizatriptan benzoate, Ion-activated, Gellan gum, HPMC E15 LV, Brain delivery, Migraine
2. Ponkshe, P., et al., Nasal and Pulmonary Drug Delivery Systems, in In-Vitro and In-Vivo Tools in Drug Delivery Research for Optimum Clinical Outcomes. 2018, CRC Press. p. 79-134.
3. BEGLEY, D.J., The Blood‐brain Barrier: Principles for Targeting Peptides and Drugs to the Central Nervous System. Journal of pharmacy and pharmacology, 1996; 48(2):136-146.
4. Jelkmann, M., et al., A gellan gum derivative as in-situ gelling cationic polymer for nasal drug delivery. International Journal of Biological Macromolecules, 2020.
5. Rupenthal, I.D., C.R. Green, and R.G. Alany, Comparison of ion-activated in situ gelling systems for ocular drug delivery. Part 1: physicochemical characterisation and in vitro release. International journal of pharmaceutics, 2011; 411(1-2):69-77.
6. Cao, S.-l., Q.-z. Zhang, and X.-g. Jiang, Preparation of ion-activated in situ gel systems of scopolamine hydrobromide and evaluation of its antimotion sickness efficacy. Acta Pharmacologica Sinica, 2007; 28(4):584-590.
7. Kaur, P., et al., In situ nasal gel drug delivery: A novel approach for brain targeting through the mucosal membrane. Artificial cells, nanomedicine, and biotechnology, 2016; 44(4):1167-1176.
8. Paul, A., K. Fathima, and S.C. Nair, Intra nasal in situ gelling system of lamotrigine using ion activated mucoadhesive polymer. The open medicinal chemistry journal, 2017; 11:222.
9. Ahmed, O.A. and S.M. Badr-Eldin, In situ misemgel as a multifunctional dual-absorption platform for nasal delivery of raloxifene hydrochloride: formulation, characterization, and in vivo performance. International Journal of Nanomedicine, 2018; 13:6325.
10. Menzel, C., et al., Nasal drug delivery: design of a novel mucoadhesive and in situ gelling polymer. International Journal of Pharmaceutics, 2017; 517(1-2):196-202.
11. Agrawal, M., et al., Stimuli-responsive In situ gelling system for nose-to-brain drug delivery. Journal of Controlled Release, 2020.
12. Sabale, A.S., A.D. Kulkarni, and A.S. Sabale, Nasal In Situ Gel: Novel Approach for Nasal Drug Delivery. Journal of Drug Delivery and Therapeutics, 2020; 10(2-s):183-197.
13. Vigani, B., et al., Recent Advances in the Development of In Situ Gelling Drug Delivery Systems for Non-Parenteral Administration Routes. Pharmaceutics, 2020; 12(9):859.
14. Yang, S.C., et al., Body distribution in mice of intravenously injected camptothecin solid lipid nanoparticles and targeting effect on brain. Journal of controlled release, 1999; 59(3):299-307.
15. Alam, S., et al., Development and evaluation of thymoquinone-encapsulated chitosan nanoparticles for nose-to-brain targeting: a pharmacoscintigraphic study. International journal of nanomedicine, 2012; 7:5705.
16. Javia, A. and H. Thakkar, Intranasal delivery of tapentadol hydrochloride–loaded chitosan nanoparticles: formulation, characterisation and its in vivo evaluation. Journal of microencapsulation, 2017; 34(7):644-658.
17. Jang, K.-I. and H.G. Lee, Stability of chitosan nanoparticles for L-ascorbic acid during heat treatment in aqueous solution. Journal of agricultural and food chemistry, 2008; 56(6):1936-1941.
18. Guideline, I.H.T., Stability Testing Guidelines: Stability Testing of New Drug Substances and Products. ICH Q1A (R2)(CPMP/ICH/2736/99), 1999.
19. Ali, J., et al., Development and validation of a stability-indicating HPTLC method for analysis of antitubercular drugs. Acta Chromatographica, 2007; 18:168.
20. Branch, S.K., Guidelines from the international conference on harmonisation (ICH). Journal of pharmaceutical and biomedical analysis, 2005; 38(5):798-805.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).