PRODUCTION AND COMPARISON OF CURCUMIN

NANOPARTICLES IN SONIFICATION BATH AND

PROBE SONICATOR

INTERNSHIP REPORT

Submitted by

SURIYA PRASATH. M

In partial fulfillment for award of the degree

of

BACHELOR OF TECHNOLOGY

in

PHARMACEUTICAL TECHNOLOGY

UNIVERSITY COLLEGE OF ENGINEERING

BIT CAMPUS, ANNA UNIVERSITY
TIRUCHIRAPPALLI -620024

ANNA UNIVERSITY: CHENNAI 600 025

JULY 2023
 University College Of Engineering (BIT Campus)
Anna University, Tiruchirappalli-620 024
Vision
 To transform students into competent professional and responsible citizens by
focusing on assimilation, analysis, synthesis and dissemination of knowledge to meet
the societal needs.
Mission
 Impart quality education to meet the needs of the profession and society. Attract and
develop talented and committed human resource and provide an environment
conducive to innovation and research.
 Facilitate effective interactions among faculty, students, premier educational
institutions, R & D laboratories, industries, alumni and other stack-holders. Practice
and promote high standards of professional ethics, transparency and accountability
and team spirit and entrepreneurial skills.

Department Of Pharmaceutical Technology (NBA

Accredited) Vision
 To provide quality education, foster research and development in Pharmaceutical
Technology, evolve innovative solutions for industrial problems and serve for
humanity, upraise the department to reach the apex of glory in pharma education and
research to be cognizant of as Centre for Excellence.
Mission
 Deeply inoculate the treasure of pharmacy education and research into the
inquisitorial minds of students through practicing with state of the art infrastructural
facilities to instigate the multi- disciplinary expertise to meet the needs of
pharmaceutical and allied industries.
 Provide a dynamic educational experience, create outreach opportunities and
empower them to become leaders of profession.
 Advocate the responsibility to contribute for the improvement in public health by
developing and translating concepts into practice within the state and beyond
Program Specific Objectives (PSOs)
a. Develop active pharmaceutical ingredients, drug intermediates and
pharmaceutical products.
b. Apply data driven decisions and predictive analytical tools in smaller and
larger molecule producing industries.
c. Identify technical issues related to the design, manufacturing of
chemicals & pharmaceuticals and provide effective interdisciplinary
solutions.
d. Adapt continuously changing technologies and play pivotal professional
role in sustainable societal development

Program Outcomes (POs)

After completion of graduation in Pharmaceutical Technology, the students will

be able to demonstrate the ability to
a. Apply knowledge of mathematics, science and technology in the Discipline.
b. Identify, formulate, research literature, and analyze complex engineering
problems for its solution
c. Design and develop system processes that meet the
specified needs with appropriate consideration for public health, safety,
cultural, societal, and environmental.
d. Design the experiments, its analysis and interpretation of data,
synthesis of the information using research-based knowledge for
complex problems.
e. Use modern engineering tools, software and equipment to meet the
needs in the area of Pharmaceutical Technology.
f. Apply reasoning informed by the contextual knowledge to assess
societal, health, safety, legal, and cultural issues relevant to the
professional engineering practices.
g. Apply knowledge of the impact of pharmaceutical technology
solutions in a societal and global context.
h. Demonstrate ethical principles and commitment to
responsibilities and norms of the Pharmaceutical technology practices.
i. Work effectively as an individual and as well as
memberin teams of diversified professionals.
j. Communicate effectively
k. Understand the philosophies of project management
principles in Pharmaceutical technology.
 l. Showcase urge for self-education and life-long learning.

Program Educational Objectives (PEOs)

a. To prepare students for prosperous spectrum of career avenues in academia,

advanced research, industries of pharmaceutical technology, biomedicine,
biotechnology, law, business and government and other pharmaceutical
pursuits through dissemination of knowledge and proficiency in engineering
and technology fundamentals related to pharmaceutical technology and the
ability to solve problems.
b. To transfuse in students the sense of confidence in professional endeavours
application of the derived knowledge and appreciation of economic impact in a
societal context.
c. To provide collegial and nurturing environment for the students to realize the
professional, ethical obligations and their concern to protect the health and
welfare of the public and to be accountable for the social and environmental
impact of their practice.
d. To create an enjoyable educational environment in which students participate
in multidisciplinary, team oriented, open-ended curricular and co-curricular
activities that prepare them to work either individually and as an integrated
team member.
e. To facilitate the students to gain the wisdom of fundamentals and advances to
practice Pharmaceutical technology and interdisciplinary research as career of
constructive service to society and higher learning.
 ACKNOWLEDGMENTS

I am humbled and immensely grateful to extend my heartfelt gratitude to the remarkable individuals and
esteemed institutions whose unwavering support and guidance have been the driving force behind the
success of my internship journey.

 Dr. PRABHAKARAN SHANMUGAM, Scientist, CSIR Madras complex. He guided me the

project in a Very kind manner. He was with us in the every process and he is very involved
during the time of the project. Your contributions have been integral to the successful
culmination of my internship.

 Dr. A. ROBERT SAM, SR Principal Scientist, Scientist in charge. Your tireless guidance,
continuous mentorship, and the wealth of project-related information you provided have been
the pillars of strength throughout my internship journey.

 Dr. T. SENTHIL KUMAR , Dean, University College of Engineering, Anna University, BIT
Campus, Tiruchirappalli: I am honored to express my deepest appreciation for your consistent
support, which has been an invaluable source of motivation throughout my internship
expedition.

 I express my sincere gratitude and respect to our Mentor Dr. S . LATHA , Assistant Professor ,
Department of Pharmaceutical Technology for her unflinching support, encouragement and
motivation and constantly support throughout the intership.

 I consider it a great privilege and honor to have an opportunity to do internship at CSIR Madras
Complex. I convey my heartiest thanks to Dr . PRABHAKARAN SHANMUGAM for giving us
the opportunity to do an internship with your institution.

 My beloved parents: Your unconditional support, endless cooperation, and steadfast

encouragement have been the cornerstone of my achievements. I am profoundly
grateful for your role in making this internship journey a reality.

Yours Sincerely

DINESH S


CONTENTS:

1. Introduction I
2. Introduction II
3. Aim
4. Objectives
5. Materials required
6. Procedures
7. Results
8. Discussion
9. Changes made from original proposal
10. Conclusion
11. Reference
 INTRODUCTION I

Embarking on the academic voyage of my third year in B.Tech Pharmaceutical Technology

at the University College of Engineering, BIT campus, Trichy-24, I have done project on
Curcumin nanoparticles and I exposed to many things in this internship. I had the privilege for
doing internship in CSIR Madras Complex from June 19 to July 19. . Beyond fulfilling a
curriculum requisite, this experiential sojourn enabled me to synergize theoretical knowledge with
practical application, fostering an evolution as both a scholar and an aspiring pharmaceutical
technologist.

OBJECTIVES OF INTERSHIP:

1. TO WORK ON NANOPARTICLES: Nanoparticles are one of the growing industry

in this generation and the future will be majorly based on this technology. We have
exposed to this field nanotechnology and done gained some knowledge in it.

2. TO ENHANCE BIOAVAILABILITY: Our main goal of this internship is to improve

the Curcumin Bioavailability of this drug by decreasing the particle size of it.
 OVER VIEW OF THE INSTITUTION

CSIR – CSIO COMPLEX, CHENNAI

ABOUT THE INSTITUTION:

The Council of Scientific & Industrial Research, established in 1942 with Corporate Office at New
Delhi, and a network of 38 national laboratories spread over the country is a premier R&D Organisation
in India providing S & T inputs to a diverse spectrum of economic, industrial and societal sectors.
The R & D activities covers fields from aerospace engineering to ocean sciences, molecular biology to
metallurgy, chemicals to mining, food to petroleum & leather to environment.
In order to foster multidisciplinary research and to cater to the requirements of the southern region, five
major laboratories established regional centres at Madras in a single campus which is known as CSIR
MADRAS COMPLEX (CMC).
 CSIR MADRAS COMPLEX CHENNAI

CENTRAL SCIENTIFIC INSTRUMENTS ORGANISAION

The CSIO Chennai Centre was established in 1965 to meet the repair and maintenance requirements of
scientific and industrial instruments of the southern region. Its objective is to reduce the down time of
sophisticated instruments in research institutes, universities, laboratories, industries and hospitals etc.
CSIR - CSIO Chennai Center started the design and development work in respect of instruments where
spares were either too costly or not available.
CSIR- CSIO established latest facilities for conducting energy audits and studies to help the industries
in the energy conservation and waste minimization. An instrument calibration laboratory for testing and
certification was also established.
Under Human Resource Development (HRD) activity, the center conducts technology based
entrepreneur development programs and training courses for instrument users on the operation, handling
and preventive maintenance of instruments. CSIO Chennai Centre conducts Management Development
Program on Energy Management System & Instrumentation for international participants under
ITEC/SCAAP program of Ministry of External Affairs.

Vision:
To be a leader at the National level for designing and developing scientific and industrial instruments,
systems and devices; play a lead role in providing support for testing & calibration services; developing
skilled manpower by way of training on state-of-the-art instrument technologies and be a custodian of
instrumentation activity in the country.

Mission:
CSIR CSIO Chennai Centre is participating in CSIR SERC AcSIR’s M. Tech program in Renewable
Energy. This novel program in renewable energy is aimed at equipping the next generation of young
Indians in science/engineering with the right skills to tackle the toughest challenges facing in the area of
Energy
INTRODUCTION II :

Curcumin, also known as diferuloylmethane, is an active component in the golden spice

turmeric (Curcuma longa) and in Curcuma xanthorrhiza oil. It is a highly pleiotropic
molecule that exhibits antibacterial, anti-inflammatory, hypoglycemic, antioxidant,
wound-healing, and antimicrobial activities. Due to these properties, curcumin has been
investigated for the treatment and supportive care of clinical conditions including
proteinuria, breast cancer, multiple myeloma, depression, and Non Small Cell Lung
Cancer (NSCLC). Despite proven efficacy against numerous experimental models, poor
bioavailability due to poor absorption, rapid metabolism, and rapid systemic
elimination have been shown to limit the therapeutic efficacy of curcumin. Curcumin is
under investigation for the treatment and supportive care of various clinical conditions
including mucositis, rectal cancer, prostate cancer, chronic schizophrenia, and Mild
Cognitive Impairment. ntravenous application of 25 mg/kg bw curcumin to rats resulted
in an increase in bile flow by 80 and 120% . In the rat model of inflammation, curcumin
was shown to inhibit edema formation. In nude mouse that had been injected
subcutaneously with prostate cancer cells, administration of curcumin caused a marked
decrease in the extent of cell proliferation, a significant increase of apoptosis and
micro-vessel density. Curcumin may exert choleretic effects by increasing biliary
excretion of bile salts, cholesterol, and bilirubin, as well as increasing bile solubility.
Curcumin inhibited arachidonic acid-induced platelet aggregation in vitro.
Curcumin acts as a scavenger of oxygen species, such as hydroxyl radical, superoxide
anion, and singlet oxygen and inhibit lipid peroxidation as well as peroxide-induced
DNA damage. Curcumin mediates potent anti-inflammatory agent and anti-
carcinogenic actions via modulating various signalling molecules. It suppresses a
number of key elements in cellular signal transduction pathways pertinent to growth,
differentiation, and malignant transformation; it was demonstrated in vitro that
curcumin inhibits protein kinases, c-Jun/AP-1 activation, prostaglandin biosynthesis,
and the activity and expression of the enzyme cyclooxygenase (COX)-2.
 AIM:
The aim of this project was to increase its bioavailability and water
solubility of the drug named curcumin by decreasing the particle size
of curcumin by the sonication bath and probe sonication method and
to compare it’s result obtained from them.
OBJECTIVES:
The main objective of this project is to decrease it’s particle size.
There are two main method of decreasing the particle size

MATERIALS REQUIRED:
Bath Sonication in Dichloromethane:

The required materials for Bath Sonication are.

1. 1,320 microliter of tween 80

2. 8 milliliter of Dichloromethane
3. 100 milligram of curcumin
4. Infusion pump
5. 500 milliliter of beaker
6. 200 milliliter of distilled water.

The instruments required for Bath Sonication are

1. Bath sonicator
2. Vacuum oven
3. Centrifuge.
Bath Sonication in Acetone:
The required materials for Bath sonication are

1. 1,320 microliter of tween 80

2. 8 milliliter of Acetone
3. 100 milligram of curcumin
4. Infusion pump
5. 500 milliliter of beaker
6. 200 milliliter of distilled water

The instruments required for Bath Sonication are

1. Bath Sonicator
2. Vacuum oven
3. Centrifuge.
Probe sonication in Acetone:
The required materials for probe sonication are

1. 1,320 microliter of tween 80

2. 8 milliliter of Acetone
3. 100 milligram of curcumin
4. Infusion pump
5. 500 milliliter of beaker
6. 200 milliliter of distilled water

The instrument required for probe sonication is

1. Probe Sonicator
2. Hot air oven
3. Centrifuge.
Methodology for preparation of Curcumin nanoparticles using Bath Sonication:
BATH SONICATION

Prepare a solution by dissolving 100 mg of curcumin in 8 ml of Dichloromethane in a

standardized beaker.

Then add 1,320 micro liter of tween 80 in the 200 ml distilled water in a 500 ml beaker.
Stir it carefully with the stir rod.

Now place the beaker which contains tween 80 solution in the bath Sonicator then heat
and sonicate for 20 minutes.

In-between the 20 minutes, add 1 ml of curcumin solution in the beaker which is

keptin the sonication bath for every 2 minutes and after 20 minutes again sonicate
the solution for 20 minutes without heating.

After sonication process, we have to precipitate the particles which is present in the
solution by the process called centrifugation using centrifuge instrument at 5000 rpm
for about 10 minutes and after centrifugation place the solution in the vacuum oven
toevaporate the solution from 200 ml to around 20 ml to get the fine sonicated
particles.
CALCULATIONS:
0.5 percent p/v curcumin solution is
0.5 g in 100 ml, then
0.02 g in 4 ml .
Therefore we have to add 40 mg of curcumin in 8 ml
Dichloromethane.
0.7 percent p/v tween 80 solution
The density of tween 80 =1.06 g/ cm cube
Density = mass / volume
Volume =660 microliter.
Therefore we have to add 1320 microliter of tween 80 to thedistilled
water.

PREPARATION OF CURCUMIN NANOPARTICLES IN ACETONE

MEDIUM:
In this project we are comparing the two values of results by formulating
nanoparticles of curcumin by ultra Sonicator bath inDichloromethane and
Acetone medium.
The same procedure is followed in formulating the nanoparticles of
curcumin in Acetone medium expect the usage of Dichloromethane we are
using Acetone medium to dissolve curcumin powder to increase its
solubility.
DIAGRAM OF INSTRUMENTS:

PROBE SONICATOR BATH SONICATOR

These are the instruments which are used to convert larger particles into smaller particles and
helps in increasing the solubility and bioavailability of particles. The main diferrence between
the two instrument is bath sonicator has both heating and sonicating ability where probe
sonicator only has sonication ability.
Methodology for preparation of Curcumin nanoparticles using Probe Sonication:

PROBE SONICATION

Place the tween 80 solution which is prepared by adding 1,320 microliter oftween 80 into
200 ml of distilled water in the tFocus system.

After placing the tween 80 solution in to the tFocus system, set the amplitude ofthe tFocus
system up to 60 percentage of amplitude .

We have to add 1 ml of curcumin solution which is prepared by dissolving 100 mgof

curcumin powder into 8 ml of Acetone medium for every 2 minutes.

After the sonication for 20 minutes turn off the tFocus system and place thebeaker in
the hot air oven for drying the solution.

Keep the sonicated solution in the hot air oven over night to get the fine
nanoparticles from the solution.
INSTRUMENTS:
NANOPARTICLE ANALYSER INSTRUMENT
PRINCIPLE:
The nanoparticle analyser work under the principal of dynamic light scattering
method which is caused by Brownian moment. The principal of Brownian motion
it that the particles present in the solution has a constant solutions with the
solvent. Due to its collisions, particle gain some amount of energy and starts
moving. As a results, smaller particlehas more energy as compared to the larger
particles in the solution. So the smaller particles move faster than the larger
particles. Here by knowing one parameters we can find the diameter of the
particles using the Stokes-Einstein equation.

Stokes-Einstein equation
is
 D=KT/6πR
1. Where K is Boltzmann constant,
2. T is temperature,
3. D is translational diffusion coefficient and
4. R is hydrodynamic diameter.

WORKING MECHANISM:

A single frequency laser is directed to the sample contained in a cuvette. If there

are particles in the sample, the incident laser light getsscattered in all directions.
The scattered light is detected at a certain angle over time and this signal is used to
determine the diffusion coefficient and the particle size by the Stokes-Einstein
equation. The incident laser light is usually attenuated by a gray filter which is
placed between the laser and the cuvette.
 APPLICATIONS:
Nano particle size analyser is used: to characterize the size of carbon
nanotubes in dispersion, to measure and control particle size distribution of
cement, to detect oversize particles in inks and paints, tomeasure protein size etc.

DIAGRAM OF NANOPARTICLE ANALYZER:

Here we have to anlayse the particle size of both the samples ofprobe sonication
and bath sonication by the nano particle analyser instrument.
 UV VISIBLE SPECTROSCOPY
PRINCIPLE :

The Principle of UV-Visible Spectroscopy is based on the absorption of ultraviolet

light or visible light by chemical compounds, which results in the production of
distinct spectra. Spectroscopy is based on the interaction between light and matter.
When the matter absorbs the light, it undergoes excitation and de-excitation,
resulting in the production of a spectrum. When matter absorbs ultraviolet
radiation, the electrons present in it undergo excitation. This causes them to jump
from a ground state (an energy state with a relatively small amount of energy
associated with it) to an excited state (an energy state with a relatively large
amount of energy associated with it). It is important to note that the difference in
the energies of the ground state and the excited state of the electron Is always
equal to the amount of ultraviolet radiation or visible radiation absorbed by it
.Beer-Lambert Law derivation helps us define the relationship between the
intensity of visible UV radiation and the exact quantity of substance present.

Beer-Lambert Law Formula is

The Beer-Lambert law is expressed as:

 A = εLc
1. Where A is the amount of light absorbed for a particular
wavelength by the sample
2. Ε is the molar extinction coefficient
3. L is the distance covered by the light through the solution
4. C is the concentration of absorbed particles.
WORKING MECHANISM:
There are many parts in the instrumentation of the UV-Vis spectroscopy system,
which are indispensable in the functioning of the UV-Vis spectrophotometer.
Ultraviolet-visible spectrophotometer system focuses electromagnetic radiation
from the light source to the sample. Depending on the configuration set in the
system, light is transmitted through the sample or reflected off it. Then, the light
is collected from the sample through reading. Initially, light is focussed into the
entrance slit of the monochromator from the source.
Monochromator uses dispersing elements, namely optical grating to separate the
light by wavelength. The light is passed into a charged coupled device (CCD),
which is made up of individual tiny detectors, hence the intensity of light at each
wavelength will be measured. CCD is read-off to a computer and the result
obtained is a spectrum, which shows the intensity of each wavelength of light.
Spectrophotometers are able to measure the electromagnetic radiation from
ultraviolet to infrared. Spectrum will show the intensity of light versus the
wavelength.

APPLICATIONS:
The applications of UV-Vis spectroscopy are enormous. The followingare the
main fields in which UV-Vis spectroscopy is used:

1. DNA & RNA analysis

2. Pharmaceutical analysis
3. Bacterial culture
4. Beverage analysis.
DIAGRAM OF UV SPECTROSCOPY:

Here we have to analyze the concentration of the both sample which is produced
by formulation in probe sonication and bath sonication by UV Spectroscopy
method and the values are noted.
RESULTS:

NANOPARTICLE ANALYSER:
Probe sonication 1:
The values of Probe Sonication 1 obtained from the nanoparticleanalyser is
1. Diameter= 7335.8 nm
2. Polydispersity Index=2.364

3. Intensity=59735

ANALYSIS OF NANOPARTICLES:
Probe sonication 2:
The values of probe sonication 2 is obtained from the nanoparticle analyser is
1. Diameter= 4300.2 nm
2. Polydispersity Index= 1.839
3. Intensity= 70013
ANALYSIS OF NANOPARTICLES:
Bath Sonication 1:
The values of bath sonication 2 is obtained from the particle sizeanalyser is
Diameter= 1855.6 nm
Polydispersity Index= 0.914
Intensity= 50622
ANALYSIS OF NANOPARTICLES:
UV VISIBLE SPECTROSCOPY:
The Nanoparticles present in the all three samples observe around the wave
length of 400 to 450 nanometer.

ANALYSIS OF NANOPARTICLES:
 DISCUSSION :

We have discussed about how to increase the bioavailability of the drugs by decreasing
the particle size. In this project we have started to decrease the particle size by using two
instruments namely Tfocus and Bath sonification. The aim of this project is to increase
the effectiveness of drugs because the drugs with smaller particles is more powerful then
the drugs with the larger particles. we actually compared the end results for formulation of
both method is that which one is more effective to cure some of the disease which cannot
be cured. we also discussed about the nanomedicine which is the use of nanoparticles
such as gold and silver nanoparticles which is used as carriers to affected area.

CHANGES MADE FROM ORIGINAL PURPOSE:

Actually we have made a big change in this project is that we have used two medium
for dissolving curcumin nanoparticles because the curcumin is dissolved more in
acetone than the dichloromethane.

CONCLUSION:
From the final results, we came to know that both the instruments reduced the particles
into nanoparticles but from the results, the particle size of sonification is less than the
Tfocus instrument. This final result is due the bath sonification instrument has the
ability To heat and sonicate at the same time whereas in Tfocus method is only used to
Sonicate the drug particles. Tfocus instrument does not has the ability to heat. The
Difference in the size of nanoparticles is less than 4 nanometers. If we made some
Changes in the Tfocus instrument is that by bringing the heating option in this instrument
We may see great formulation results.as we compared to the bath sonification formulation
Results.
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