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