FORMULATION AND CHARAC TERIZATION OF SOLID LIPID

www.wjpps.com Vol 9, Issue 2, 2020.

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Gaikwad et al. World Journal of Pharmacy and Pharmaceutical Sciences

FORMULATION AND CHARAC TERIZATION OF SOLID LIPID

NANOPARTICLES OF QUETIAPINE FUMARATE TO IMPROVE

SOLUBILITY

Maya Y. Gaikwad*, Amol S. Deshmukh and Vijay R. Mahajan

SMBT College of Pharmacy, Nandi- Hills Dhamangaon, Nashik Maharashtra, India.

ABSTRACT

Quetiapine fumarate is an antipsychotic drug with plasma half-life 6

hr. and having poor oral bioavailability (9%) because of first pass

metabolism. The aim of the present study was to develop an optimal

SLN formulation of Quetiapine fumarate to improve solubility and oral

bioavailability. Liquid dispersion of SLN were framed with Oleic acid

as oil phase, Cremophor RH 40 and Tween 20 as surfactant and

Transcutol P as co-surfactant after screening several vehicles. The

prepared formulation was constructed by using phase diagram to

optimize the system. Solidification of SLN was done by using spray

drying technique using Aerosil 200 as solid carrier. The drug release study shows that the

release of Quetiapine fumarate was enhanced in SLN formulation as compared to plain drug

and marketed formulation. Stability study shows that there was no sign of change in drug

content was observed.

KEYWORDS: Pseudoternary phase diagram, Quetiapine fumarate, SLN, Oral

bioavailability.

INTRODUCTION

Currently, majority of the new drug molecules being discovered are lipophilic and exhibits

poor water solubility which results in low bioavailability, intra and inter subject variation and

lack of dose proportionality. Limited water solubility have a challenge in developing optimum

oral solid dosage form in terms of formulation design, bioavailability and marketing of new

pharmaceutical products. Several formulation approaches have been approved to overcome

these challenges either by means of altering the solubilization or maintaining the drug in

WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

SJIF Impact Factor 7.632

Volume 9, Issue 2, 943-963 Research Article ISSN 2278 – 4357

*Corresponding Author

Maya Y. Gaikwad

SMBT College of Pharmacy,

Nandi- Hills Dhamangaon,

Nashik Maharashtra, India.

Article Received on

06 Dec. 2019,

Revised on 27 Dec. 2019,

Accepted on 17 Jan. 2020

DOI: 10.20959/wjpps20202-15453


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dissolved form throughout gastric transit time. These strategies may consist of the surfactants,

cyclodextrins, Micronization, salt formation pH change, nano size delivery, solid dispersions

and permeation enhancer. In fact, most commonly used approaches are, digestion of the active

pharmaceutical ingredient into inert lipids such as oils and surfactant dispersions, SLN, self-

emulsifying formulations, emulsions and liposomes.[1]

Solid lipid nanoparticle (SLN) is the term introduced in early 90s which is an alternative carrier

system to traditional colloidal carriers corresponds to emulsions, liposomes, polymeric nano

and microparticles. SLN are sub-micron colloidal carriers ranging from 50 to 1000 nm, which

are composed of physiological lipid, dispersed in water or in aqueous surfactant solution. SLN

suggest distinctive properties like large surface area, high drug loading, small in size and the

interaction of phases at the interface that also have likely to improve performance of

pharmaceuticals. The reasons for the enhancing interest in lipid based system are –

1. Lipids improve oral bioavailability of drug and ultimately decreases plasma profile

variability.

2. Better characterization of lipoid excipients.

3. Enhanced capacity to address the key issues of technology transfer and manufacture scale

up.[2]

The majority of orally administered drugs gain access to the systemic circulation by absorption

into portal circulation. However, some extremely lipophilic drugs (log P > 5, solubility in TG

> 50 mg/ml) gain access to the systemic circulation via lymphatic route, which avoids hepatic

first pass metabolism. Therefore, highly metabolized lipophilic drugs are suitable candidates

for solid lipid nanoparticles, a lipid based delivery. Compounds showing increased

bioavailability in the presence of lipids (dietary or lipid-based formulation) are absorbed via

the intestinal lymph as they are generally transported in association with the long chain TGs

lipid core of intestinal lipoproteins which is formed in the enterocyte after re-esterification of

free FAs and MGs. Short chain TGs are mostly absorbed in the portal blood. Hence it is likely

that the drug transport via the lymphatic needs co administration of lipid to stimulate

lipoprotein formation.[3]

Quetiapine Fumarate is chemically 2-[2-(4-{2-thia-9azatricyclo[9.4.0.0{3,8}]pentadeca-

1(11),3(8),4,6,9,12,14-heptaen10-yl}piperazin-1-yl)ethoxy]ethan-1-ol is an atypical

antipsychotic agent which acts as an antagonist of dopamine and serotonin receptors.


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Quetiapine Fumarate is an antipsychotic BCS class II drug having low solubility and high

permeability. It is reported to have very low oral bioavailability (9%) reason being its limited

absorption due to moderate solubility in water and extensive hepatic metabolism.[4] Possible

methods to avoid first-pass metabolism include transdermal, buccal, rectal, and parenteral

routes of administration. Oral route is the most frequently used and ideal route for the delivery

of drugs, although some factors like pH of GIT, residence time, and solubility can affect drug

absorption or availability by this route. Lymphatic delivery is an alternative option to avoid

first-pass metabolism in oral drug delivery. The main purpose of the lymphatic system is to

facilitate absorption of long-chain fatty acids via chylomicron formation. Two different lipid-

based approaches are known to enhance the lymphatic transport, which comprise of

construction of a highly lipophilic prodrug and incorporation of drug in a lipid carrier.[5]

MATERIALS AND METHODS

Present investigation was carried out in the year 2019 at S. M. B. T. College of Pharmacy,

Dhamangaon, Pune University, and Maharashtra, India.

Materials: Quetiapine fumarate was received as a gift sample from Akums Drugs and

Pharmaceuticals Ltd., Haridwar. Lipids including Capryol 90, Isopropyl myristate, Oleic acid,

Castor oil and Olive oil; Surfactants including Tween 20, Tween 80, Span 80, Labrasol and

Cremophor RH 40; Co- surfactants including Ethanol, Isopropyl alcohol, Propylene glycol,

PEG 400 and Transcutol P all are received from Research Lab Fine Chem Industries and

Gattefosse Foundation Lab Industries. All the chemicals and solvents used were of analytical

grade.

Method

UV Method: Weighed accurately 10 mg of Quetiapine fumarate and transferred to 100 ml

volumetric flask. The drug was dissolved in methanol and make up the volume. This was

used as the standard stock solution for further dilutions. Appropriate quantities of aliquots

(0.2 ml to 1 ml) of the standard stock solution were taken in 10 ml volumetric flask. The

absorbance of solutions was recorded at 248 nm by using the Thermo-fisher UV-2600 double

beam spectrometer.[6]

Solubility studies: Screening of excipients can be done by determining the equilibrium

solubility of Quetiapine Fumarate in different oil, surfactant, and co-surfactant. The solubility

of in different oils, surfactant and co-surfactant was determined using shake flask method. An


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excess amount of Quetiapine fumarate was added to each vial containing 2ml of each

excipients, and mixed by vortexing in order to facilitate proper mixing of Quetiapine

fumarate with the vehicles. Vials ware then shaken for 48hrs in a thermostatically controlled

shaking water bath at 37± 1°C followed by equilibrium for 24 hrs. in order to separate the

undissolved drug, the supersaturated sample was centrifuged at 3000 rpm for 10 min. The

supernatant was then filtered using a membrane filter (0.45μm, Whatman filter, and paper) and

suitably diluted with methanol. The drug concentration was obtained via UV validated method

at 248nm.[7]

Construction of Phase Diagram: In water titration method, the mixture of oil and surfactant

(A+B) /co-surfactant (S/CoS) at certain volume ratios was diluted with water in a drop wise

manner. The ratios of surfactant (A+B) /co-surfactant were prepared in specific manner, i.e.

1:1, 2:1, and 3:1(w/w). Each of these ratios was mixed with increasing percentage of oil, i.e.

10%, 20%, 30% up to 90% to get phase diagram. Phase diagram was constructed using

Chemix School 4_00.[8]

Preparation of Liquid dispersion of SLN: Liquid dispersion of SLN were prepared by

dissolving drug in lipid heated above its melting point followed by addition of surfactant

(A+B) and co-surfactant maintaining same temperature by pouring in ice cold water, vortex the

mixture to get aqueous dispersion of SLN.[9]

Characterization of Liquid dispersion of SLN

Drug content determination: Amount of drug present in aqueous dispersion formulation

was determined by UV Spectrometric method. Weighed accurate quantity of liquid

formulation equivalent to 10 mg of drug (Quetiapine fumarate) in 100ml volumetric flask and

was diluted with methanol to make up volume upto 100 ml. Further 1 ml of the solution was

diluted to 10 ml using methanol to make 10μg/ml solutions. The drug content was analysed

by taking UV absorbance at 248 nm.[10]

Drug release study: The in vitro dissolution study of liquid formulations and plain drug were

carried out using dissolution test apparatus no. 1 as per IP. Quantity equivalent to 10 mg of

liquid formulation was added to dissolution media. Samples of 5 ml at 5 min interval were

withdrawn at regular time 5 min to 60 min and filtered using Whatman filter paper. An equal

volume of respective dissolution medium was added to maintain the volume constant. Drug

release was analyzed using UV-spectrophotometer at 248 nm.[11,12]


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Precipitation assessment: Liquid formulations was diluted upto 100 times with distilled

water with continuous stirring on magnetic stirrer to form emulsion. Precipitation was

evaluated by visual inspection of the resultant emulsion after 24 hrs. The formulations were

categorized as clear (transparent, or transparent with bluish tinge), non-clear (turbid), stable

(no precipitation at the end of 24 hours, or unstable (showing precipitation within 24 hrs).[13]

Refractive Index: Refractive index proved to the transparency of formulation. The refractive

index of the system is measured by Abbe refractometer by placing drop of solution on slide

and recording the refractive index. Oleic acid, Tween 20, Transcutol P and liquid formulation

were noted.[14]

Zeta potential measurement: Liquid formulation containing 10 mg of Quetiapine fumarate

was diluted to 20 ml with distilled water in a flask and was mixed gently by inverting the

flask. The particle size so formed was determined by dynamic light scattering (DLS)

technique using Zetasizer (Nano ZS, Malvern Instruments, UK). With the zeta potential

Electrophoretic mobility was also determined.[15]

Stability study of aqueous dispersion of SLN.[16-18]

1. Thermodynamic Stability Studies: The liquid formulation were filled in vials and was

kept at different temperature condition to check the stability of the formulation. This study

was performed for 3 month and any change in the formulation was reported. The sample

were kept at various temperature condition like-

25°C-Room temperature

40°C-Stability Oven

2. Centrifugation test: Prepared liquid formulation was centrifuged at 3500 rpm speed for

about 30 min. The phase separation after 30 min was observed. If the formulation shows

the phase separation then the formulation is unstable and if no phase separation is

observed the formulation is stable and hence, can be used for the further studies.

Solidification of Aqueous Dispersion Of Sln

Solidification can be done by spray drying technique. Colloidal Silicon Dioxide (Aerosil 200)

was used as the carrier for the conversion of liquid formulation to SLN. Aerosil 200 (5 gm)

was dissolved in 150 ml methanol by magnetic stirring. The liquid formulation (10 gm) was

then added with constant stirring, and the solution was kept at 50°C for 10 min to obtain a

good emulsion. After the completion of drying process, fraction of dried Nanoparticles were


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collected from different parts of spray dryer, i.e. drying chamber, first cyclone separator and

collector attached to it. These fractions were then mixed in polybag for 15 min to ensure the

uniform mixing of blend.

RECONSTITUTION PROPERTIES OF SOLID LIPID NANOPARTICLES

Visual observation: SLN (100 mg) was introduced into 100 ml of double distilled water in a

glass beaker that was maintained at 37°C and the contents mixed gently using a magnetic

stirrer. The tendency to emulsify spontaneously and progress of emulsion droplets were

observed with respect to time.[19]

Particle size: Particle size of SLN was determined by laser scattering technique using Malvern

zetasizer (Zetasizer Ver.6.20 Serial No. MAL 1051945 Malvern Ltd). All measurements were

performed at a 25±2°C.[15]

CHARACTERIZATION OF SLN[19-21]

Powder Flow Properties: Spray dried product was evaluated for Angle of repose, bulk

density, Tapped density, Compressibility index, and Hausner ratio.

Drug content determination: Drug content of SLN was determined by adding sufficient

amount of methanol to spray dried powder then the UV absorbance was measured at 248nm.

By the calculation 150 mg of SLN contain 10 mg of the drug, so for the drug content

determination 150 mg of SLN powder were taken.

In-vitro Dissolution Study: The in-vitro dissolution study of SLN was carried out using

dissolution test apparatus no. 1 as per IP. Quantity equivalent to 10 mg of SLN powder added

to dissolution media. Samples of 5 ml at specific time interval was withdrawn and filtered

using 0.45µm filter paper. An equal volume of respective dissolution medium was added to

maintain the volume constant. Drug release from sample was analyzed using UV-

spectrophotometer at 248 nm.

Differential Scanning Calorimetry: The physical state of Quetiapine fumarate in SLN was

characterized by the differential scanning calorimetry (DSC Instruments, METTLER, and

STAR SW 10.00). The samples were placed in standard aluminium pans, and dry nitrogen

was used as effluent gas. All samples were scanned at a temperature range speed of 5°C/min.

the DSC thermogram of Quetiapine fumarate, SLN containing Quetiapine fumarate and

Aerosil 200 with each other.[23]


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Scanning Electron Microscopy: Surface topography of the SLN was investigated by

Scanning Electron Microscopy (SEM).

Powder X-ray Diffraction: X-ray powder diffraction pattern of SLN containing

Colloidal Silicon Dioxide were recorded. Peaks present in the sample were measured.

Stability study of SLN powder[16-18]

1. Visual observation: The SLN powder were filled in vials and was kept at different

temperature condition to check the stability of the formulation. This study was performed

for 1 month and any change in the formulation was reported. The sample were kept at

various temperature condition like-

-20°C=Defreeze

25°C=Room Temperature

40°C=Stability Oven

2. Drug Content: Drug content was determined from initial level to 1 month. The samples

kept at different temperature condition at every weeks were added to sufficient amount of

methanol and the UV absorbance was measured at 248 nm. The results from initial level

to 1 month was compared.

RESULT AND DISCUSSION

Solubility study: Solubility of Quetiapine fumarate on different oil, surfactant and co-

surfactant are shown in FIG. 1, 2, and 3. Solubility study of Quetiapine fumarate in lipid/oil

revel that oleic acid show very good solubility as compare to others.

Fig. 1: Solubility of Quetiapine Fumarate in Different Lipids/Oils.


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Depending on the solubility study of Quetiapine fumarate in surfactants like Span 80, Tween

20 and Cremophor RH 40 showed more solubility than the other surfactants.

So these surfactants were selected for the further study.

Fig. 2: Solubility of Quetiapine Fumarate in Surfactants.

Depending on solubility of Quetiapine fumarate in different co-surfactant like Transcutol P

and Propylene glycol showed more solubility than other co-surfactants.

Fig. 3: Solubility of Quetiapine Fumarate In Co-Surfactants.


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Table 1: Preliminary Screening of Oil/Lipid, Surfactants With Different Co-

Surfactants.

Oil Surfactant Co-surfactant Observation

Oleic acid

Tween 20

Transcutol P Clear aqueous dispersion

Ethanol Turbid dispersion

Propylene Glycol Phase separation

Tween 80

Transcutol P Turbid dispersion

Ethanol Phase separation


Cremophor RH 40

Transcutol P Clear aqueous dispersion

Ethanol Turbid dispersion


Table 2: Finally Selected Excipients for The Sln Formulation.

Oil Surfactant Co-surfactant

Oleic acid Tween 20

Transcutol P Cremophor RH 40

Construction of Pseudo-Ternary Phase Diagram

A pseudo ternary phase diagram of the investigated system Oleic acid (Lipid), Tween 20 and

Cremophor RH 40 (Surfactant), Transcutol P (Co-surfactant).

For the construction of Pseudo ternary phase diagram different ratio of Surfactant and co-

surfactant are prepared (Smix). Ratios are prepared as follows-

Lipid + Smix (1:1)

Lipid + Smix (2:1)

Lipid + Smix (3:1)

Water was added in a drop wise manner to each oily mixture under proper magnetic stirring at

37°C until the mixture became clear at a certain point. The concentrations of the components

were recorded in order to complete the pseudo ternary phase diagram, and then the contents of

lipid, surfactant, and water at appropriate ratios were selected based on these results. The

boundaries of the emulsification region in the phase diagrams were determined by connecting

the points representing formation of the nanoparticles.

Ternary phase diagram of different ratio are shown in FIG. 4, 5, 6.


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Fig. 4: Phase Diagram Of Oleic Acid, Tween 20+ Cremophor Rh 40, Transcutol P (1:1)

and Water.

Fig. 5: Phase Diagram of Oleic Acid, Tween 20+ Cremophor Rh 40, Transcutol P (2:1)

And Water.


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Fig. 6: Phase Diagram of Oleic Acid, Tween 20+ Cremophor Rh 40, Transcutol P (3:1)

And Water.

Phase diagram indicated that the Smix ratio 1:1 and 2:1 shows less emulsification region than

the other therefore these ratios was rejected. In case of the phase diagram 3:1 shows larger

emulsification region than other ratios. Therefore the Smix ratio 3:1 will be selected for

further study.

PREPARATION OF AQUEOUS DISPERSION OF SLN

Drug Loading[22]

The aqueous dispersion of SLN formulation containing 2%w/w, 4%w/w, 6%w/w, 8%w/w,

10%w/w, 12%w/w and 14%w/w drug does not show any precipitation of drug while the

formulation containing 16%w/w drug (formulation Q8) shows precipitation within 12 hr. Thus,

in liquid formulation maximum 15%w/w drug can be loaded without any precipitation.

CHARACTERIZATION OF AQUEOUS DISPERSION OF SLN

Drug content determination

Amount of drug present in the liquid formulation was determined by UV Spectrometric

method.

Table 3: Drug Content of Different Liquid Sln Formulation.

Sr.no. Formulation

code

Drug

Content(%w/w)

1 S1 93.59

2 S2 96.86

3 S3 95.25


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Drug Release Study

In vitro drug release study was performed for Quetiapine fumarate and liquid SLN. Results

are shown in table.

Table 4: In-Vitro Drug Release Study of Quetiapine Fumarate and Liquid Sln.

Sr.no. Time

(min)

% DR

Plain Drug S1 S2

1 5 0.696 42.318 45.372

2 10 3.269 58.068 60.436

3 15 9.754 69.049 76.083

4 30 15.965 75.877 81.196

5 45 17.475 88.642 89.740

6 60 21.696 96.294 96.843

Fig. 7: Comparison of Dissolution Profile of Plain Drug, Liquid Formulation (S1 And

S2).

In vitro release study results revels that only 21.696%w/w drug was released from plain

Quetiapine fumarate filled in capsule in 60 min while 96.294%w/w, 96.843%w/w drug

release from the liquid formulation S1, S2 formulation respectively within 60 min.

Precipitation Assessment

The formulated liquid formulation diluted with the 100ml of distilled water and the diluted

formulation observed for the precipitation and results was shown in Table no. 33.

Table 5: Precipitation Assessment of Different Liquid Formulation.

Sr.no. Formulation

code Precipitation after 24 hrs.

1 S1 Transparent, clear liquid, no precipitation, stable

2 S2 Transparent, clear liquid, no precipitation, stable

3 S3 Precipitation after 24 hrs.


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From precipitation assessment S1 and S2 formulation found to be transparent, clear liquid with

no precipitation and found to be stable. S3 formulation forms whitish precipitate within 12

hrs.

Therefore S3 formulation will be rejected. S1 and S2 formulation may be selected for further

study but drug content for S1 formulation was found low therefore only S2 formulation will

be selected for further study.

Refractive Index

Refractive index of the Oleic acid, surfactant, co-surfactant and liquid formulation are shown

in table.

Table 6: Refractive Index.

Sr.no. Component Refractive Index

1 Oleic acid 1.458

2 Tween 20 1.460

3 Cremophor RH 40 1.454

4 Transcutol P 1.427

5 Liquid formulation 1.452

Zeta potential

The zeta potential is used to identify the charge of the droplet. The value of zeta potential

indicates the degree of electrostatic repulsion between particles in the dispersion. Zeta

potential measurement is shown in following table no. 7 and figure no. 8.

Table 7: Zeta Potential Measurement of Liquid Formulation.

Formulation Zeta potential Conductivity(mS/cm)

Liquid formulation (Q2) -18.8 0.536

Fig. 8: Zeta Potential Measurement.


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RECONSTITUTION PROPERTIES OF SLN

Visual observation

Reconstitution property of SLN was determined by stirring powder with distilled water for 5

min and observed visually. SLN showed rapid dispersion without any lump or agglomeration.

This dispersion when observed visually after incubation for 60 min room temperature was

well dispersed without phase separation.

Particle size determination

Particle size and polydispersity index of SLN is as follows-

Table 8: Particle Size and Polydispersity Index of Sln.

Formulation Particle size(nm) Polydispersity Index

SLN 485.8 1.000

Fig. 9: Histogram of Particle Size Distribution of Sln.

CHARACTERIZATION OF SLN

Powder flow properties

Table 9: Flow Properties of Spray Dried Product.

Sr. no. Parameter Result Inference

1 Bulk density 0.90 g/ml -

2 Tapped density 1.11 g/ml -

3 Carr’s Index 18.91% -

4 Hausner ratio 1.23 Passable

5 Angle of Repose 21.20°C Passable

The flow property of SLN was found to be passable because of floppy mass of Aerosil 200

and also it contain lipid, surfactant, co-surfactant adsorbed on Aerosil 200.


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Drug Content Determination

Table 10: Drug Content In Sln.

Sr.no. Formulation % Drug Content

1 SLN 96.45

In vitro Dissolution study

In vitro dissolution profile of Plain drug, liquid formulation, SLN, and Marketed formulation

are compared together. SLN formulation shows more % drug release than the liquid

formulation, marketed formulation and the plain drug.

Table 11: In Vitro Dissolution Data of Plain Drug, Liquid Formulation, Sln and

Marketed Formulation.

Sr.no. Time

(min)

% Drug Release

Plain drug Liquid

formulation SLN

Marketed

formulation

1 5 0.696 45.372 48.426 28.524

2 10 3.269 60.436 61.534 35.690

3 15 9.754 76.083 79.171 46.327

4 30 15.965 81.196 82.088 59.016

5 45 17.475 89.740 91.799 68.128

6 60 21.696 96.843 98.730 70.269

Fig.10: Comparison of Dissolution Profile of Plain Drug, Liquid Formulation, Sln and

Marketed Formulation.

Differential Scanning calorimetry

DSC of Quetiapine fumarate (plain drug) and its SLN were performed.


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Fig. 11: Dsc Spectra of Quetiapine Fumarate.

Fig. 12: Dsc Spectra of Quetiapine Fumarate Sln.

DSC of Quetiapine fumarate exhibits a sharp melting point at 174.27°C with onset 171.96°C

and endset or recovery at 176.54°C. The DSC of nanoparticle does not show the sharp peak.

The absence of sharp melting peak indicates that the lipids and Aerosil 200 inhibits the

crystallization of drug i.e. is in amorphous form or in solubilized form in SLN.

Scanning Electron Microscopy

Scanning Electron Microscopy (SEM) was used to determine the particle morphology of

optimized SLN.


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Fig. 13: Sem Images of Quetiapine Fumarate Sln.

Revels that the Quetiapine fumarate SLN shows irregular shape granular particle. The SEM

of Quetiapine fumarate SLN does not show any rectangular crystals of drug on the surface of

Aerosil 200 indicate that the drug present in the soluble form in lipid (SLN) formulation;

which is adsorbed on the surface of Aerosil 200.

Powder X-ray Diffraction

The X-ray diffraction pattern of Quetiapine fumarate SLN was done.


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Fig. 14: X-Ray Diffraction Peaks of Quetiapine Fumarate.

The absence of sharp peak in SLN formulation revels that the drug (Quetiapine fumarate) is

present in the amorphous form or present in solubilized form in SLN.

STABILITY STUDY

1. Stability study of aqueous dispersion of SLN

Table 12: Thermodynamic Stability Studies.

Formulation Temperature Time period

Initial 1 month 2 month 3 month

Aqueous

dispersion of

SLN

25°C

(Room Temp)

Clear and

transparent

liquid

Clear and

transparent

liquid

Clear and

transparent

liquid

Clear and

transparent

liquid

40°C

Clear and

transparent

liquid

Clear and

transparent

liquid

Clear and

transparent

liquid

Clear and

transparent

liquid

2. Centrifugation Test

Passed SLN was centrifuged at 3500 rpm for 30 min using centrifuge (Remi motors Ltd.),

there was no phase separation found.

This proves that the liquid SLN formulation are stable when subjected to centrifugation test.

Stability study of SLN powder

1. Thermodynamic Stability Studies

Stability study of SLN at Freeze temperature (-20°C) , Room temperature (25°C) and High

temperature (40°C) was done for 1 month and evaluated for following parameters.


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2. Visual Observation

Visual observation study (shown in reveals that there is no change in color observed during

stability study for 1 month.

3. Drug Content

Drug content of SLN was done after 1 month and results were shown in Table no.37. The drug

content data shows that there is no change in drug content of SLN. This proves that the

formulated SLN are stable.

Table 13: Drug Content Determination (Stability Study).

Formulation Temperature Time period

SLN powder

Initially After 1 month

-20°C 95.69

25°C 96.45 96.40

40°C 96.02

The visual observation study and Drug content determination study evidence that SLN is stable

at -20°C, 25°C, 40°C.

CONCLUSION

The optimized formulation was found to be the better formulation on the basis of results of

pseudo ternary phase diagram, in vitro drug release, particle size and other parameters. The

present study was clearly indicated that the usefulness of SLN in the improvement of the

dissolution rate and there by oral bioavailability of poorly water soluble drug Quetiapine

fumarate without incompatibility between the ingredients.

ACKNOWLEDGEMENT

The authors are thankful to Akums Drugs and Pharmaceutical Ltd. Haridwar, India for

providing a gift sample of Quetiapine fumarate and S. M. B. T. college of Pharmacy,

Dhamangaon, Nashik.

CONFLICT OF INTEREST

The authors have no conflict of interest regarding to the content of manuscript.

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FORMULATION AND CHARAC TERIZATION OF SOLID LIPID