Solid Lipid Nano particles of Alendronate Sodium
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Transcript of Solid Lipid Nano particles of Alendronate Sodium
FORMULATION AND EVALUATION OF SOLID LIPID NANOPARTICLES OF WATER SOLUBLE DRUG
ByROHIT SUMAN
Under the guidance of Miss. JAYANTHI
M. Pharm. (Ph.D.)Professor
DEPARTMENT OF PHARMACEUTICSGAUTHAM COLLEGE OF PHARMACY
BHUVANESHWARI NAGAR, R.T. NAGAR POST
BANGALORE - 560 032
CONTENTS
INTRODUCTION
OBJECTIVE
METHODOLOGY
RESULTS AND DISCUSSION
CONCLUSION
INTRODUCTION
Need for the study
Nano drug delivery
Solid Lipid Nanoparticle
Advantages of Nano Drug delivery systems
Nanoparticles
•Nanoparticles are defined as solid colloidal particles ranging in size from 10-1000nm, the active principle is dissolved, entrapped, encapsulated and to which the active principle is absorbed or attached.
•Nanoparticles represent a very promising drug delivery system of controlled and targeted drug release.
Advantage and disadvantage of Solid lipid Nanoparticles
Advantage of SLN•SLNs have better stability and easy to produce than
liposomes.• In SLNs the lipid matrix is made from physiological lipid
which decreases the danger of acute and chronic toxicity.•Possibility of controlled drug release.
Disadvantage of SLN•Poor drug loading capacity.•Drug expulsion during storage.
NEED FOR THE STUDY
•Many of the recent formulation approaches utilize Nanotechnology that is the preparation of Nanosized structures• In recent years, significant effort has been devoted to develop
nanotechnology for drug delivery, since it offers a suitable means of delivering small molecular weight drugs• SLN combines the advantages of different colloidal carriers and also
avoids some of their disadvantages. SLN can be used to improve the bioavailability of drugs,• Alendronate sodium is a BCS class III bisphosphonate, used in
treatment of osteoporosis.• Having a molecular weight of 249.096.• It having a pKa value 2.72 and plasma protein binding is 78%.• It having a bioavailability of 0.6%
OBJECTIVES
• To formulate and evaluate Solid lipid Nanoparticle of
Alendronate Sodium is to sustained the drug release and
enhance bio availability
• To formulate solid lipid nanoparticles using different
lipids
• To evaluate and characterize solid lipid nanoparticles
METHODOLOGY
•Preformulation Studies
Melting point determination
Calibration curve of Alendronate Sodium
Compatibility Studies
•Formulation of SLN
Evaluation of SLN•Determination of particle size .
•Determination of total drug content.
•Determination of drug entrapment efficiency.
•X-ray powder diffraction studies.
• In vitro release studies.
•Stability studies.
RESULTS AND DISCUSSION
•Preformulation Studies Melting Point DeterminationMelting point was found to be 234 ºC and complies with USP
standards thus indicating purity of the drug sample used.
Method of estimation Alendronate Sodium
By using UV spectrophotometric method.
Standard graph of Alendronate Sodium in Milli Q Water
Sl. No.Concentr
ation (g/mL)
Absorbance*
1 0 02 10 0.154 ± 0.0033 20 0.298± 0.0074 30 0.459 ± 0.0015 40 0.623± 0.0056 50 0.759 ± 0.002
Observations for standard curve of Alendronate Sodium in Milli Q water
Alendronate Sodium showed maximum absorbance in Milli Q
water at 565nm. The solution obeyed Beer-Lambert’s law for a
concentration range of 10g/mL to 50g/mL with a regression
coefficient of 0.9995
Concentration (µg/mL)
Abs
orba
nce
0 10 20 30 40 50 600
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8f(x) = 0.0152981818181818 xR² = 0.999827575018248f(x) = 0.0153228571428572 x − 0.000904761904762186
Calibraton curve for Alendronate Sodium
CONCENTRATION (µg/mL)
ABSO
RBAN
CE
Standard curve of Alendronate Sodium in Milli Q water
Compatibility studies
DSC of Dynasan
DSC of physical mixture of Alendronate and Dynasan DSC of Poloxamer
DSC of physical mixture of Alendronate and Poloxamer
DSC of pure drug sample of Alendronate
Lipid and Drug physical mixture Peak (˚C) Enthalpy (J/g)
Alendronate + Glyceryl Monostearate 130.87 372.48Alendronate + Compritol 129.58 106.12Alendronate + Dynasan 128.82 258.41
DSC of physical mixture of drug and lipids
Formulation of SLN of Alendronate Sodium by Hot homogenization method
•Hot homogenization is carried out at temperatures above the melting point of the lipid
• In this method lipids are melted ,aqueous phase containing a drug was added drop by drop to oil phase and homogenize for 10 minute to produced primary emulsion.
•Primary emulsion was added to aqueous surfactant drop by drop under high homogenization to give (w/o/w)
Formulation of SLN of Alendronate Sodium
Ingredients F1 F2 F3 F4 F5 F6 F7 F8 F9Alendronate Sodium
(mg) 10 10 10 10 10 10 10 10 10
Glycerol
momosterate100 150 200 - - - - -
Glyceryl Behanate- - - 100 150 200 - - -
Glyceryl trimyristate- - - - - - 100 150 200
Poloxamer %(w/v) 0.5 1 1.5 1.5 0.5 1 0.5 1 1.5
Water (mL) 2 2 2 2 2 2 2 2 2
Temperature(°C) 70 70 70 70 70 70 70 70 70
RPM 15000 5000 10000 5000 10000 15000 5000 10000 15000
Time (Min) 20 30 10 20 30 10 10 20 30
Evaluations of SLN of Water Soluble
Drug(Alendronate Sodium)
Formulation % Yield Drug Content
% Entrapment Efficiency
Particle Size (nm)
F1 45.87 50.4 45.87 144.9
F2 37.96 44.15 37.96 238.9
F3 45.91 44.74 45.91 245.3
F4 51.70 57.19 51.70 2204
F5 42.13 48.86 42.13 157.8
F6 39.07 45.86 39.07 1552
F7 51.24 56.76 51.24 202.2
F8 61.82 80.46 61.82 556.0
F9 48.97 58.21 48.97 879.5
F1 F2 F3 F4 F5 F6 F7 F8 F90
102030405060708090
68.18 67.85 68.25 70.4363.89
51.47
75.93 80.46
62.82
DR UG CO N T E N T o f s l n
FORMULATION CODE
DRU
G C
ON
TEN
T
Drug Content of all formulations
F1 F2 F3 F4 F5 F6 F7 F8 F90
10203040506070
45.8737.96
45.9151.7
42.1339.07
51.24
61.82
48.97
%Entrapment Efficiency
Entrament Efficiency
FORMULATION CODE
% E
NTRA
PMEN
T EF
FICI
ENCY
% Entrapment Efficiency of all nine formulations
1 2 3 4 5 6 7 8 90
200400600800
1000
144.9 238.9 245.3 220.4 157.8 155.2 202.2
556
879.5
Particle Size (nm)
Formulation Code
Parti
cle S
ize (µ
m)
Particle Size of all nine formulations
F1 F2 F3 F4 F5 F6 F7 F8 F90
10203040506070
0
45.8737.96
45.9151.7
42.13 39.07
51.2961.82
48.97
% Yield
Formulation Code
% Y
ield
% Yield of all nine formulations
In-vitro release studies of prepared SLN
• Conducted by using dialysis membrane
• Dissolution media: phosphate buffer pH 6.8
• USP type II
In vitro drug release studies of SLN of Alendronate Sodium Time
(Hrs)
F1 F2 F3 F4 F5 F6 F7 F8 F9
0.5 6.197 6.674 7.638 4.843 5.367 5.5274 7.471 6.384 7.790
1 15.697 14.959 15.553 14.737 17.077 16.838 22.828 18.979 23.573
1.5 17.285 17.491 16.605 15.251 17.807 17.223 23.864 19.241 24.078
2 20.553 22.153 21.601 17.514 20.607 18.121 24.693 20.115 25.897
3 21.895 23.752 23.442 20.188 22.676 19.788 26.558 21.338 27.109
4 23.996 26.150 25.808 23.067 24.258 24.020 27.801 22.648 30.141
5 28.081 28.281 27.386 26.153 25.110 27.611 30.288 25.530 33.172
6 35.819 34.782 32.382 34.174 33.996 36.204 32.875 27.626 50.551
7 45.203 41.922 40.796 43.019 40.569 41.077 55.365 46.056 60.454
12 64.694 64.782 65.382 65.645 65.278 66.214 74.743 60.992 62.475
24 78.933 77.837 78.004 77.677 77.815 79.552 85.416 65.708 65.506
48 85.702 85.297 82.343 85.493 85.970 81.347 91.115 74.617 85.109
0.5 1 1.5 2 3 4 5 6 7 12 24 480
102030405060708090
F1F2F3
Times (hrs)
%C
DR
Comparative In-vitro dissolution study of F1-F3
0.5 1 1.5 2 3 4 5 6 7 12 24 480
102030405060708090
100
F4F5F6
Time (hrs)
% C
DR
Comparative In-vitro dissolution study of F4 – F6
0.5 1 1.5 2 3 4 5 6 7 12 24 480
20
40
60
80
100
F7F8F9
Time (hrs)
% C
DR
Comparative In-vitro dissolution study of F7 – F9
TEM
TEM of formulation F7
XRD of Formulation F7
XRD
For optimized formulation F7
The Particle size was found to be 202nm
Transmissions electron microscopy (TEM) studies revealed that
the SLNs formed were nearly spherical with smooth surface.
XRD of F7 is amorphous
• This study confirms that the hot homogenization technique is
suitable, simple and reproducible for the preparation of SLN of
Alendronate Sodium.
CONCLUSION
The present research work was designed to
develop solid lipid nanoparticles of Alendronate
Sodium. Preparation of solid lipid nanoparticles of
Alendronate Sodium to sustained release of the
drug.
BIBLIOGRAPHY•Garud A, Singh D, Garud N,International Current Pharmaceutical
Journal 2012, 384-393.•Yadav N, khatak S, Sara U V S , International Journal of Applied
Pharmaceutics solid lipid nanoparticles, 2013.•Nikam S,Chavan M, Sharma P H, Innovations in Pharmaceuticals
and Pharmacotherapy 2014, 365-376.• Ekambaram P, Sathali A A Hand Priyanka K, solid lipid
nanoparticles: Scientific review chemical Communication 2012, 80-102.
Thanks