This document discusses the formulation and evaluation of solid lipid nanoparticles (SLNs) of the water soluble drug alendronate sodium. Nine SLN formulations were developed using different lipids and production parameters. The SLNs were characterized for particle size, drug content, entrapment efficiency, in vitro drug release, XRD and TEM. Particle size ranged from 144.9-879.5 nm. Drug content and entrapment efficiency ranged from 44.15-80.46% and 37.96-68.18% respectively. In vitro drug release extended up to 24 hours with formulations F7, F8 and F9 showing maximum release. XRD and TEM confirmed the amorphous nature and spherical shape of

1. FORMULATION AND EVALUATION OF SOLID LIPID
NANOPARTICLES OF WATER SOLUBLE DRUG
By
ROHIT SUMAN
Under the guidance of
Miss. JAYANTHI
M. Pharm. (Ph.D.)
Professor
DEPARTMENT OF PHARMACEUTICS
GAUTHAM COLLEGE OF PHARMACY
BHUVANESHWARI NAGAR, R.T. NAGAR
POST
BANGALORE - 560 032

2. CONTENTS
 INTRODUCTION
 OBJECTIVE
 METHODOLOGY
 RESULTS AND DISCUSSION
 CONCLUSION

3.  Need for the study
 Nano drug delivery
 Solid Lipid Nanoparticle
 Advantages of Nano Drug delivery systems

4. •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.

5. 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.

6. 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%

7. • 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

8. •Preformulation Studies
Melting point determination
Calibration curve of Alendronate Sodium
Compatibility Studies
•Formulation of SLN

9. •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.

10. •Preformulation Studies
Melting Point Determination
Melting 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.

11. Standard graph of Alendronate Sodium in Milli Q Water
Sl. No.
Concentr
ation
(g/mL)
Absorbance*
1 0 0
2 10 0.154 ± 0.003
3 20 0.298± 0.007
4 30 0.459 ± 0.001
5 40 0.623± 0.005
6 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 10g/mL to 50g/mL with a regression
coefficient of 0.9995
y = 0.0153x
R² = 0.9995
y = 0.015x - 0.009
-0.2
0
0.2
0.4
0.6
0.8
1
0 10 20 30 40 50 60
ABSORBANCE
CONCENTRATION (µg/mL)
Calibraton curve for Alendronate
Sodium
Standard curve of Alendronate Sodium in Milli Q
water

12. 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

13. Lipid and Drug physical mixture Peak (˚C) Enthalpy (J/g)
Alendronate + Glyceryl Monostearate 130.87 372.48
Alendronate + Compritol 129.58 106.12
Alendronate + Dynasan 128.82 258.41
DSC of physical mixture of drug and lipids

14. 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)

15. Formulation of SLN of Alendronate Sodium
Ingredients
F1 F2 F3 F4 F5 F6 F7 F8 F9
Alendronate Sodium
(mg)
10 10 10 10 10 10 10 10 10
Glycerol
momosterate
100 150 200 - - - - -
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

16. 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

17. 68.18 67.85 68.25 70.43
63.89
51.47
75.93 80.46
62.82
0
20
40
60
80
100
F1 F2 F3 F4 F5 F6 F7 F8 F9
DRUGCONTENT
FORMULATION CODE
DRUG CONTENT OF SLN
Drug Content of all formulations
45.87
37.96
45.91
51.7
42.1339.07
51.24
61.82
48.97
0
10
20
30
40
50
60
70
F1 F2 F3 F4 F5 F6 F7 F8 F9
%ENTRAPMENTEFFICIENCY
FORMULATION CODE
%Entrapment Efficiency
Entrament Efficiency
% Entrapment Efficiency of all nine formulations
144.9
238.9 245.3 220.4 157.8 155.2 202.2
556
879.5
0
500
1000
1 2 3 4 5 6 7 8 9
ParticleSize(µm)
Formulation Code
Particle Size (nm)
Particle Size of all nine formulations
0
10
20
30
40
50
60
70
F1 F2 F3 F4 F5 F6 F7 F8 F9
0
45.87
37.96
45.91
51.7
42.13 39.07
51.29
61.82
48.97
%Yield
Formulation Code
% Yield
% Yield of all nine formulations

18. In-vitro release studies of prepared SLN
• Conducted by using dialysis membrane
• Dissolution media: phosphate buffer pH 6.8
• USP type II

19. In vitro drug release studies of SLN of Alendronate
SodiumTime
(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

20. 0
10
20
30
40
50
60
70
80
90
0.5 1 1.5 2 3 4 5 6 7 12 24 48
%CDR
Times (hrs)
F1
F2
F3
Comparative In-vitro dissolution study of F1-F3
0
10
20
30
40
50
60
70
80
90
100
0.5 1 1.5 2 3 4 5 6 7 12 24 48
%CDR
Time (hrs)
F4
F5
F6
Comparative In-vitro dissolution study of F4 – F6
0
20
40
60
80
100
0.5 1 1.5 2 3 4 5 6 7 12 24 48
%CDR
Time (hrs)
F7
F8
F9
Comparative In-vitro dissolution study of F7 – F9

21. TEM
TEM of formulation F7
XRD of Formulation F7
XRD

22.  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.

23. 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.

24. 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 AA Hand Priyanka K, solid lipid
nanoparticles: Scientific review chemical Communication 2012, 80-
102.