Formulation and Evaluation of Niosomal in situ Nasal Gel of a Serotonin Receptor Agonist, Buspirone Hydrochloride for the Brain Delivery via Intranasal Route.

BACKGROUND: Buspirone Hydrochloride is an anxiolytic agent and serotonin receptor agonist belonging to azaspirodecanedione class of compounds used in the treatment of anxiety disorders. It has short half-life (2-3h) and low oral bioavailability (4%) due to extensive first pass metabolism. OBJECTIVE: The nasal mucosa has several advantages viz., large surface area, porous endothelial membrane, high blood flow, avoidance of first-pass metabolism and ready accessibility that lead to faster and higher drug absorption. Keeping these facts in mind, the objective of the present study was to develop Buspirone hydrochloride loaded niosomal in-situ nasal gel. METHODS: Buspirone hydrochloride niosomal in situ nasal gel was formulated, optimized and evaluated with the objective to deliver drug to the brain via intranasal route. Niosomes were prepared by thin film evaporation method and optimized using32 factorial design. Niosomes were characterized for particle size, zeta potential, entrapment efficiency and in vitro drug release. Buspirone hydrochloride loaded niosomes were further incorporated into Carbopol 934P and HPMC K4M liquid gelling system for the formation of in situ gel. The resultant solution was assessed for various parameters, viz., gelling time, gelling capacity, viscosity at pH 5 and pH 6. RESULTS: The vesicle size of all niosomal suspension batches ranges between 168.3 -310.5 nm. The vesicle size of optimized niosomal suspension F5 batch is 181.9±0.36nm. For F5 batch, the value of zeta potential was found to be -15.4 mV; this specifies that prepared niosomes have sufficient surface charge to prevent aggregation of the vesicles. % entrapment efficiency for all batches was found in the range 72.44±0.18% to 87.7±0.66%. The cumulative percent release of niosomal suspension ranges from 66.34±0.39 to 84.26±0.26%. Ex vivo permeation of Buspirone hydrochloride through the sheep nasal mucosa showed that 83.49% w/w drug permeated after 8 h. The SEM and Zeta potential studies showed the formation of stable vesicles. CONCLUSION: Thus, the application of niosomes proved the potential for intranasal delivery of Buspirone hydrochloride over the conventional gel formulations. Overall intranasal drug delivery for Buspirone hydrochloride has been successfully developed.

Development and evaluation of tamarind seed xyloglucan-based mucoadhesive buccal films of rizatriptan benzoate.

Mucoadhesive buccal films were developed using tamarind seed xyloglucan (TSX) as novel mucoadhesive polysaccharide polymer for systemic delivery of rizatriptan benzoate through buccal route. Formulations were prepared based on 3(2) factorial design with concentrations of TSX and carbopol 934P (CP) as independent variables. Three dependent variables considered were tensile strength, bioadhesion force and drug release. DSC analysis revealed no interaction between drug and polymers. Ex vivo diffusion studies were carried out using Franz diffusion cell, while bioadhesive properties were evaluated using texture analyzer with porcine buccal mucosa as model tissue. Results revealed that bilayer film containing 4% (w/v) TSX and 0.5% (w/v) CP in the drug layer and 1% (w/v) ethyl cellulose in backing layer demonstrated diffusion of 93.45% through the porcine buccal mucosa. Thus, this study suggests that tamarind seed polysaccharide can act as a potential mucoadhesive polymer for buccal delivery of a highly soluble drug like rizatriptan benzoate.