Formulation and Charcterization of Pectin-Nano particles Loaded In-Situ Intranasal Gel of Venlafaxine Hydrochloride

Abstract

The purpose of the present investigation was to prepare venlafaxine (VLF) loaded pectin nano particles (NPs) incorporated into thermo sensitive insitu gelling solution that will undergo gelation at nasal temperature, to enhance the uptake of VLF to brain via intranasal (i.n.) delivery. VLF loaded pectin NPs were prepared and characterized for particle size, zeta potential, encapsulation efficiency and in vitro drug release. The low bioavailability and systemic side effects exhibited by conventional oral dosage forms of venlafaxine hydrochloride due to high hepatic first pass metabolism of the drug may be overcome by the use of in situ gel-forming systems that are instilled as solution into the nasal cavity that will result in brain targeting via olfactory region. Further formulation of venlafaxine hydrochloride into nanoparticles will result in sustained drug delivery for a longer duration that is best suitable for anti depressive therapy. Nanoparticles were prepared using ionic gelation technique in which pectin was used as polymeric phase and MgCl2, CaCl2, ZnCl2 as divalent cation and different pH conditions of pectin solution (pH 2.0, pH 4.0, pH 6.0) were used for the formulation of nanoparticles. Results of preliminary batches revealed that nanoparticles prepared using MgCl2 as a cation and pH of pectin solution at 4.0 was found to possess lowest particle size, optimum zeta potential, optimum % entrapment efficiency and complete drug release at 24 hours. For the systematic optimization of the prepared nanoparticles a 32 full factorial design was used with Pectin:MgCl2 concentration ratio and pH of thepectin solution as independent variables and particle size, zeta potential, % entrapment efficiency and % drug release at 24 hours as dependent variables. Results of different batches prepared using factorial design revealed that nano particles prepared using 0.5% pectin solution, 0.5 % MgCl2 and pH 4.0 of pectin solution had lowest particle size (170.8 nm), optimum zeta potential (-28.9 mV), optimum % entrapment efficiency (76.2%) and complete drug release at 24 hours (90.36%). The prepared nanoparticles were incorporated into thermosensitive insitu gelling solution (25% poloxamer 407 and 0.5% HPMC K4M) that undergoes gelation within < 40 seconds at 31oC. The results demonstrated that the nanoparticulate insitu gelling suspension can be used for nasal administration of venlafaxine hydrochloride to enhance the CNS targetting, bioavailability and patient compliance.