This document summarizes a study on enhancing the aqueous solubility of the chemotherapy drug Bendamustine using sodium benzoate as a hydrotropic solubilizing agent. Sodium benzoate (2M concentration) was able to solubilize Bendamustine freely in water. The linearity of Bendamustine was determined to be between 4-10 μg/ml. The developed method was found to be accurate, reproducible, economical and avoids the use of toxic solvents. The method offers an alternative for determining Bendamustine concentration.

1. HYDROTROPIC SOLUBILIZATION AND
LINEARITY PROFILE OF BENDAMUSTINE
Santosh Karajgi and Shripad Potadar,
Department of Pharmaceutical Quality Assurance,
BLDEA’s SSM College of Pharmacy and Research Centre, Vijayapur
586103 (Affiliated to RGUHS Bengaluru)

2. WELCOME

3. ABSTRACT:
Introduction:
Bendamustine is a poorly water soluble drug used
as an alkylating agent for the chemotherapy
treatment of cancers.

4. Objectives:
Objectivs of the present study was an effort made to enhance
the aqueous solubility of Bendamustine and to validate.
Materials:
A study on the hydrotropic solubility and linearity profile of
the drug Bendamustine was performed by using Sodium
Benzoate as the solubilizing agent as Bendamustine is poorly
soluble in water.

5. Methods:
Bendamustine was soluble freely in water when 2M
Sodium Benzoate was used as a solubilizing agent.
Bendamustine shows maximum absorption wavelength
at 255nm in First derivative mode of measurement using
Shimazdu UV Spectrophotometer 1800 spectronic
model.

6. Results:
At the absorption maximum of 255nm, Bendamustine shows a
linear response over the range of 4μg/ml to 10μg/ml
concentration with equation for straight line slope 0.12 and
intercept 1.21. The assay values were found to be accurate
with low standard deviation values and low values of co
efficient of variation.
0
0.5
1
1.5
2
2.5
3
3.5
4 μg/ml 6 μg/ml 8 μg/ml 10 μg/ml
Series 1
Linear (Series 1)

8. Parameter Condition
Solubilizing agent Sodium Benzoate
Concentration 2M
Solubility of Bendamustine 1mg/ml
Range 4 to 10μg/ml
Regression Equation y=0.12X+1.21
LOD 0.009242μg/ml
LOQ 0.04233μg/ml
Assay 98.89% (n=5)
Assay S.D. 0.0723
Assay CoV 0.9885
Optimum conditions for Linear
Graph

9. Conclusion:
The present newly developed method offers an accurate,
reproducible, linear, economical, time saving method
with a suitable concentration range for the determination
of Bendamustine using an environment friendly method
which avoids the use of harmful and toxic solvents.
ACKNOWLEDGEMENTS:
The authors are grateful to the funding agency, Rajiv
Gandhi University of Health Sciences, Bangalore,
Karnataka and this work is supported by the Research
Grant sanctioned by RGUHS. (Grant number: 17P061
wide University notification number
RGU/ADV.RES/BR/001/2017-18 dated 19.04.2017).

10. REFERENCES:
1. Jeffrey Colledge, Margaretha Olthoff, inventors; Astellas DG, assignee. Oral
dosage forms of Bendamustine. EP2575784A1. 2010 Jun 02.
2. Maheshwari RK and Moondra S. A novel method for the quantitative determination
of Aceclofenac in bulk drug and tablet using Sodium Benzoate as a hydrotropic
solubilizing agent. Journal of Advanced Pharmaceutical Technology and Research
2010; 1(1): 78-82.
3. Ji Young Kim, Sungwon Kim, Michelle Papp, Kinam Park, Rodolfo Pinal.
Hydrotropic solubilization of poorly water soluble drugs. Journal of Pharmaceutical
Sciences 2010; 99(9): 3953-3965.
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February 2020
5. https://www.ich.org/page/quality-guidelines [ICH, accessed on 27th February
2020].
6. https://www.fda.gov/media/71021/download [USFDA, accessed on 27th February
2020].