Tetrabenazine reduces chorea symptoms associated with Huntington’s disease by depleting monoamines in pre-synaptic vesicles. It exhibits low aqueous solubility and undergoes first pass metabolism due to which it has low oral bioavailability. The aim of present work was to formulate intranasal tetrabenazine loaded nanoemulsion for better management and treatment of hyperkinesia related with Huntington’s disease. A quality by design (QbD) technique was employed as statistical multivariate approach for formulation and optimization of nanoemulsion. Optimized formulation showed droplet size of 106.80 ± 1.96 nm with polydispersity index (PDI) value of 0.198 ± 0.005 and -9.63 ± 0.63 mV zeta potential. Ex-vivo drug permeation studies were carried out and found that the formulation has an augmented permeation by 1.68 times as compared to tetrabenazine suspension. MTT assay on neuro-2a cell lines showed that tetrabenazine loaded nanoemulsion displayed better cell viability than placebo and aqueous drug solution at ½ × C_max, C_max and 2 × C_max. Pharmacokinetic parameters in brain after intranasal administration of tetrabenazine nanoemulsion were found to be C_max = 3.497 ± 0.275 μg/mL, AUC₀₋₁₂ = 29.196 ± 0.870 μg h/mL and elimination rate constant (k_e) = 0.097 ± 0.012 h⁻¹ where as in plasma the pharmacokinetic parameters were C_max = 1.400 ± 0.084 μg/mL, AUC₀₋₁₂ = 12.925 ± 0.340 μg h/mL and k_e = 0.061 ± 0.010 h⁻¹. Histopathological studies of porcine nasal mucosa showed that nasal mucosa remains intact when treated with tetrabenazine loaded nanoemulsion. Thus it can be concluded from study that optimized nanoemulsion formulation of a tetrabenazine was robust and its delivery through nasal route is a viable alternative to other routes of administration for treatment of hyperkinesia associated with Huntington’s disease.

四苯那嗪通过消耗突触前囊泡中的单胺来减轻与亨廷顿舞蹈病相关的舞蹈病症状。它显示出低的水溶性，并且由于其口服生物利用度低而经历了首过代谢。当前工作的目的是配制鼻内四苯那嗪纳米乳剂，以更好地管理和治疗与亨廷顿氏病相关的运动亢进。设计质量（QbD）技术被用作统计多元变量方法，用于纳米乳液的配制和优化。优化的配方显示液滴尺寸为106.80±1.96 nm，多分散指数（PDI）值为0.198±0.005和-9.63±0.63 mV zeta电位。离体进行了药物渗透研究，发现与丁苯那嗪悬浮液相比，该制剂的渗透增加了1.68倍。在神经2a细胞系上的MTT分析表明，在½× C _max，C _max和2× C _max下，丁苯那嗪负载的纳米乳剂比安慰剂和药物水溶液表现出更好的细胞活力。被发现在丁苯那嗪纳米乳剂的鼻内给药后大脑的药物动力学参数是Ç_最大 = 3.497±0.275微克/毫升，AUC _0-12 = 29.196±0.870微克H / mL和消除速率常数（ķ _ë）= 0.097±0.012ħ ^{- 1个}其中与血浆中一样，药代动力学参数为C _max  = 1.400±  0.084μg / mL，AUC _0-12 = 12.925±0.340μgh / mL和k _e  = 0.061±0.010 h ^-1。猪鼻黏膜的组织病理学研究表明，用丁苯那嗪负载的纳米乳剂治疗时鼻黏膜保持完整。因此，从研究中可以得出结论，丁苯那嗪的优化纳米乳剂配方是健壮的，并且其通过鼻途径的递送是治疗与亨廷顿氏病相关的运动亢进的其他给药途径的可行替代方案。