Design, Development and Characterization of Nanoemulsion Containing Rutin for Nose to Brain delivery

Mr. Sagar Kishor Savale (Department of Pharmaceutics)

Introduction Optimized batch results

In the present investigation, Rutin-loaded Nanoemulsion(RU-NE) were prepared to enhancing CNS delivery for the
treatment of brain tumor. RU is highly lipophilic drug having a low oral bioavailability of 4%. RU-NE were prepared by
Spontaneous emulsification method with Ethyl Oleate, Tween 80 and Polyethylene glycol 400 as a Oil, surfactant and co-
surfactant respectively. Response surface methodology (RSM) using the central composite rotatable design (CCRD) model
was used. Three independent factors such as Oil concentration (X1), Surfactant Concentration (X2), Co-surfactant
concentration (X3) were used. Parameters investigated include dependant factors Droplet size, and Drug Content. RU-NE
were formulated and characterized by Differential scanning calorimetry (DSC) and Transmission electron microscopy
(TEM). The optimized RU-NE were transparent appearance, thermodynamically stable with average droplet size of 228.60
nm and % drug content of 94.77 %. The In vitro and ex vivo release studies of optimised NEs were conducted. Accelerated
stability studies showed that there was no significant change in the mean droplet size and % drug content after storage at Figure 3: In vitro drug release profile Figure 4: ex vivo drug release profile of
25 2C/60 5% RH for the period of three months, thus demonstrating a promising perspective for nose to brain of RU-NE (n=3, mean SD) RU-NE (n=3, mean SD)
delivery of poorly water-soluble RU. pH 6.4 simulated Formulation Iso propyl alc.

Methodology

1 Selection of drug delivery system, drug and excipients

Preformulation study
2 Figure 5: Histopathological Study On Sheep Nasal Mucosa
Experimental design by Central composite rotatable design
3
Accelerated stability studies
4 Formulation of NE by Spontaneous emulsification technique
Table 2: Stability study of RU-NE in terms of Droplet size, PDI and %
5 Characterization and evaluation of prepared RU-NE Drug content (mean SD, n=3)
Formulation of optimized batch Stability Test period
6
parameter
7 In vitro diffusion studies and In vitro Cytotoxicity studies 0 month 1 month 2 month 3 months
ex vivo study MDS (nm) 2280.027 229.6 1.80 229.4 0.03 230.1 0.013
8
PDI 0.189 0.89 0.197 1.83 0.195 0.92 0.262 1.045
9 Solid state characterization (TEM, DSC and IR) % DC 94.72 1.14 92.02 0.41 90.98 1.05 90.98 1.05

10 Accelerated stability studies Conclusion

Nose to Brain delivery In this Nano-drug delivery system, RU is successfully incorporated
Formulation Batches into NE by Spontaneous emulsification method with high drug
content due to its high lipophilicity. The RU-NE were formulated
Table 1: Formulation batches by CCRD-RSM design & Result Analysis using central composite response surface methodology by fitting
Sr. Con. Of oil Con. Of Con. Of Droplet Drug quadratic model to the response data. The results shows that drug
No (mcl) Surfactant (ml) Cosurfactant (ml) size Content
loaded Nanoemulsion for intranasal is very a promising approach for
delivering drug to CNS for the treatment of brain tumour.
(nm) (%)
1 200 1.00 7 239.47 90.08 Future Perspectives
2 200 1.00 9 228.60 94.77
Future studies of RU-NE should aim to address a number of challenges such
3 200 0.50 7 352.50 55.65
as Preclinical and clinical studies in relevant to animal models should be
4 200 0.50 9 250.15 88.90 Response surface plots by the Design
performed. Clinical Study in cancer infected patient Long- term toxicity
5 180 1.00 9 275.40 71.55 Expert software
6 180 1.00 7 316.69 58.00 studies should be carried out beyond proof- of-concept studies. Long-term
A)RSM showing the effect of the concentration of
7 180 0.50 7 412.58 43.96 total Oil & Smix on Droplet size storage stability is also requires for clinical application. After performing all
B)RSM showing the effect of the concentration of
8 180 0.50 9 300.01 60.61 these studies, in near future, RU-NE will Be the king of pharmaceutical
total Oil & Smix on Drug Content
market.
Solid state characterization
A B
Reference
1. Sagar K. savale. 2015. A Review - Self Nanoemulsifying Drug Delivery
System (SNEDDS). International Journal of Research in Pharmaceutical
and Nano Sciences, 4(6), pp.385-397.
2. Sagar Savale, et al. 2017. Nose to Brain: A versatile mode of drug
delivery system. Asian Journal of Biomaterial Research, 3(1), pp. 16-38.
Figure 1: DSC: A: Rutin , B: Physical Figure 2: TEM of RU-NE
mixture & C: Rutin NE Formulation