Formulation and Characterization of Nanostructured Lipid Carriers of Rizatriptan Benzoate-Loaded In Situ Nasal Gel for Brain Targeting

Intranasal route provides large surface area, avoids first-pass metabolism, and results in improved drug absorption. Intranasal delivery targets the drug to the brain for treatment of central nervous diseases viz migraine. The objective of the study was to formulate in situ nasal gel containing rizatriptan benzoate (RB)-loaded nanostructured lipid carriers (NLCs). NLCs were prepared by melt-emulsification ultrasonication method and optimized using 3(2) factorial design. Optimized NLCs were spherical with particle size of 189 nm, high drug encapsulation efficiency (84.5%), and 83.9% drug release at the end of 24 h. RB-loaded NLCs were incorporated into the liquid Carbopol 934P and Poloxamer 407 liquid gelling system to obtain in situ gel formation. The resultant product was assessed for gelling capacity, viscosity, and mucoadhesive strength. In vivo pharmacokinetic studies revealed significant therapeutic concentration of drug in the brain following intranasal administration with C-max value of 5.1 ng/mL and area under the curve value of 829 ng/(min center dot mL). Significantly higher values of nose to brain targeting parameters, namely, drug targeting index (2.76) and nose to brain drug direct transport (63.69%) for RB-NLCs in situ nasal gel, confirmed drug targeting to brain through nasal route. The ex vivo nasal toxicity study showed no sign of toxicity to the nasal mucosa. Thus, the application of lipid carrier-loaded in situ gel proved potential for intranasal delivery of RB over the conventional gel formulations for efficient brain targeting.

Automated summary

The intranasal route is effective in improving drug absorption and targeting the brain for treatment of central nervous diseases. This study successfully developed an in situ nasal gel containing rizatriptan benzoate-loaded nanostructured lipid carriers, which showed potential for efficient brain targeting based on pharmacokinetic and nose-to-brain targeting parameter studies.