Thermoreversible Nasal In situ Gel of Venlafaxine Hydrochloride: Formulation, Characterization, and Pharmacodynamic Evaluation
- 985 Downloads
In order to improve the bioavailability of the antidepressant drug, venlafaxine hydrochloride, in situ mucoadhesive thermoreversible gel, was formulated using Lutrol F127 (18%) as a thermo gelling polymer. Mucoadhesion was modulated by trying carbopol 934, PVP K30, HPMC K4M, sodium alginate, tamarind seed gum, and carrageenan as mucoadhesive polymers. Results revealed that as the concentration of mucoadhesive polymer increased the mucoadhesive strength increased but gelation temperature decreased. Formulation was optimized on the basis of clarity, pH, gelation temperature, mucoadhesive strength, gel strength, viscosity, drug content, diffusion through sheep nasal mucosa, histopathological evaluation of mucosa, and pharmacodynamic study in rats. Final formulation T5 containing 18% Lutrol F127 and 0.3% PVP K30 was considered as an optimized formulation. T5 released 97.86 ± 0.073% drug in 150 min with a flux of 0.1545 mg cm−2 min−1 and gelation temperature 31.17 ± 0.30°C. Histopathological evaluation of nasal mucosa revealed that T5 formulation was safe for nasal administration as it caused no damage to nasal epithelium. From the results of pharmacodynamic study, mainly forced swim test (FST), it was concluded that venlafaxine hydrochloride was more effective as an antidepressant by nasal route as in situ gel nasal drops in comparison to oral administration of equivalent dose.
Key wordslutrol F127 mucoadhesive nasal in situ gel thermoreversible venlafaxine HCl
The authors are thankful to Lupin Research Park, Pune, for providing VENH as a gift sample.
- 1.Feighner JP. The role of venlafaxine in rational antidepressant therapy. J Clin Psychiatry. 1994;55:98–100.Google Scholar
- 5.Shinde JS. In situ mucoadhesive nasal gels of metoclopramide hydrochloride: preformulation and formulation studies. J Pharm Res. 2008;1(1):88–96.Google Scholar
- 12.Jones DS, Woolfson AD, Brown AF, Coulter WA, McClelland C, Irwin CR. Design characterization and preliminary clinical evaluation of a novel mucoadhesive topical formulation containing tetracycline for the treatment of periodontal disease. J Control Release. 2000;67:357–68.PubMedCrossRefGoogle Scholar
- 13.Chng HS, Park H, Kelly P, Robinson JR. Bioadhesive polymers as platforms for oral controlled drug delivery II. Synthesis and evaluation of some swelling water-insoluble bioadhesive polymers. J Pharm Sci. 1985;74:339–405.Google Scholar
- 14.Keny RV, Lourenco CF. Formulation and evaluation of thermoreversible in situ gelling and mucoadhesive diltiazem hydrochloride liquid suppository. Int J Pharma Biol Sci. 2010;1(1):1–17.Google Scholar
- 16.Pisal S, Shelke V, Mahadik K, Kadam S. Effect of organogel components on in vitro nasal delivery of propranolol hydrochloride. AAPS PharmSciTech. 2004;5:1–9.Google Scholar
- 22.Chien YW, Su KSE, Chang SF. Nasal systemic drug delivery. New York: Marcel Dekker; 1999. p. 39–78.Google Scholar
- 23.Abd Elhady SS, Mortada N, Awad GAS, Zaki NM, Taha RA. Development of in situ gelling and mucoadhesive mebevarine hydrochloride solution for rectal administration. Saudi Pharm J. 2003;11:159–71.Google Scholar