RESEARCH ARTICLE

Solid Lipid Nanoparticle-based Gel to Enhance Topical Delivery for

Acne Treatment
Nandgude TD*, Parakhe PS, Patole VC
Department of Pharmaceutics, Dr. D.Y. Patil Institute of Pharmaceutical Sciences and Research, Pune, Maharashtra, India.

Received: 27th August, 2022; Revised: 07th November, 2022; Accepted: 03rd May, 2023; Available Online: 25th June, 2023

ABSTRACT
The aim of the present study was to investigate the treatment of acne and pimples by formulating Terminalia chebula-loaded
solid lipid nanoparticles (SLNs) based gel. Methanolic extract of T. chebula is loaded into SLN by single emulsification - Solvent
evaporation method followed by ultrasonication. Box-Behnken Design was employed for the optimization of the formulation.
The goal was to produce SLN with the highest %entrapment efficiency while also reducing particle size. Particle size (Y1)
and entrapment efficiency (Y2) were significantly affected by a few factors, including the amount of lipid, the concentration
of the surfactant, and the time of the sonication, which is considered as a critical factor during the optimization of SLN. The
average particle size T. chebula-loaded SLNs decreased with increasing concentration of surfactant. The SLNs particle size
of (201 nm) with a polydispersity index of (0.342) was obtained at significant concentration of lipid and surfactant. High
entrapment efficiency of SLN’s 70.11% revealed the ability of SLNs to incorporate a high quantity of T. chebula. Further,
When TC loaded SLN incorporated into carbopol 934 Gel, it showed initial burst release followed by a sustained release at
8 hour time span. Carbopol 934 increases the contact time of formulation via the topical route.
Keywords: Solid lipid nanoparticle, Box-Behnken design, Particle size, Entrapment efficiency, Topical route.
International Journal of Drug Delivery Technology (2023); DOI: 10.25258/ijddt.13.2.04
How to cite this article: Nandgude TD, Parakhe PS, Patole VC. Solid Lipid Nanoparticle-based Gel to Enhance Topical
Delivery for Acne Treatment. International Journal of Drug Delivery Technology. 2023;13(2):474-482.
Source of support: Nil.
Conflict of interest: None

INTRODUCTION (9.8 vs. 9.0%, respectively). P. acnes, anaerobic pathogenic

Acne vulgaris (AV) is a disorder of the pilosebaceous unit bacteria that inhabit human skin, are essential for the
that causes scarring in varying degrees as well as non- emergence of acne.2
inflammatory and inflammatory lesions like open, closed The main cause of acne vulgaris lesions is one of the irritant-
comedones and papules, pustules, nodules, respectively. In free fatty acids that are produced when lipase hydrolyzes sebum
addition to other detrimental physiological and psychological triglycerides in pilosebaceous follicles. According to earlier
effects on patient well-being and self-esteem, it frequently research, inflammation is decreased when free fatty acids are
starts in the first few years of adolescence and produces administered intradermally because they stimulate follicular
pain, scarring, and disfiguring lesions, especially in young epithelial growth. 40% acne patients taking lipase inhibitors,
patients. Primary pathogenic mechanisms lead to acne lesions, particularly those containing halopyridyl phosphorus, showed
alteration of follicular keratinization that leads to comedones; decreased levels of free fatty acids. The current study used
i.e., Propionibacterium acnes colonization of the follicles, plant extracts to study the antibacterial activity of plants
increased and changed sebum production under the control like Terminalia chebula. P. acnes demonstrated the greatest
of androgens, complicated inflammatory processes involving bactericidal reaction to methanolic extracts of T. chebula
both innate and acquired immunity.1 (750 µg).3 T. chebula is very effective in inhibiting lipase
Acne is mostly caused by the anaerobic pathogenic microbe activity. The phenolic component of T. chebula, particularly
P. acnes found on human skin. P. acnes produce a number of chebulagic acid, was discovered to be a powerful inhibitor of
different enzymes, including protease, lipase, acid phosphatase lipase activity. The solid lipid nanoparticle was first developed
and hyaluronidase, which are used to spread acne. 9.4% of in 1991. SLNs are the fastest-growing area in colloidal drug
humans on the earth, or around 650 million people have acne. delivery systems. SLN are colloidal drug carriers that range in
It affects nearly 90% of teenagers and can occasionally linger size from 50 to 1000 nm. Biodegradable/biocompatible solid
into adulthood due to an increase in testosterone hormone. lipids or a mixture of lipids can be used to make SLN delivery
Females are affected somewhat more often than males are vehicles. These SLN’s have gained great interest recently

*Author for Correspondence: [email protected]

 Nanoparticle Based Gel to Enhance Topical Delivery

because, as colloidal drug carriers, they combine the benefits

of oil emulsions, liposomes, and polymeric nanoparticles
while minimizing any of their limitations. Lipids used in SLN
preparation have approved status, such as generally recognized
as a safe (GRAS). It comprises food additives or excipients that
are acceptable for human intake due to their low toxic effects
in topical cosmetic or pharmaceutical formulations. Occlusion
characteristics are formed by film deposition on the skin, which
can aid drug diffusion through the stratum corneum.4 Figure 2: Detail method of preparation of SLN
Table 1: Independent variables and their levels
MATERIALS AND METHODS
Levels
Independent variables
Materials Low (-1) Medium (0) High (+1)
T. chebula was purchased from MPREX Healthcare Pvt Ltd, Amount of lipid (w/v) 100 150 200
Pune. Tween 80 were purchased from Lobachemie, Mumbai. Concentration of 1 2 3
Poloxamer 188 as gift sample from BASF, Mumbai. All the Surfactant (%)
solvents and reagents were of analytical grade. Before use, Sonication Time (Min) 10 15 20
distilled water was filtered using a 0.22 µm membrane filter. Table 2: Dependent variables and their range.
Dialysis bag (Pore diameter, molecular size cut off 12 to 14
Dependent Variable (Responses) Constraints (In Range)
KD, 2.4 nm DM 70 membrane) was purchased from Himedia,
Mumbai R1- Particle Size >500 (minimize)
Methods R2- % Entrapment Efficiency 55-75% (maximize)

Solubility study of drug in different lipids Optimization of TC SLN by Box-Behnken design

Several lipids, including stearic acid, glyceryl monostearate, Utilizing Design Expert Software Version Design-Expert®13,
precirol ® ATO5, cetyl alcohol, compritol ® 888 ATO were the Box Behnken design was used to optimize SLN.5 The
examined. One gram of each lipid was heated in a vial on a dependent variables Y1 and Y2 were Particle size and
magnetic stirrer at a temperature that was (5–10°C) over its Entrapment efficiency respectively. Amount of lipid, surfactant
melting point for this purpose. The vial was progressively concentration and sonication time were the independent
filled with T. chebula, which was introduced in little volumes. variables (Table 1 and 2). A total of 17 batches were developed.
After each addition, the mixture was agitated for 30 minutes. The effect of independent parameters on particle size and
The drug’s indicated saturation solubility in the corresponding entrapment efficiency was depicted using 3D plots produced
lipid was examined for transparency loss or the development by BBD. The trial runs performed using the Box-Behnken
of a brown color. design is shown in Table 3.
The lipid with the greatest drug solubility was used to Evaluation of TC loaded Solid Lipid Nanoparticles
synthesize the SLN.
All 17 batches were evaluated for parameters which are listed
Preparation of T. chebula-loaded solid lipid nanoparticles below
T. chebula-loaded SLN was prepared using single emulsification Analysis of particle size and polydispersity index (PDI)
Solvent evaporation method followed by ultrasonication.5
Particle size analyzer (Horiba SZ-100) was used to assess the
Stearic acid and T. chebula were dissolved in ethanol (organic
size of the SLN particles. SLN were diluted before analysis
phase) together. Tween 20 was used as a hydrophilic surfactant
to avoid agglomeration, and ultrasonication was used.6 The
in the aqueous phase, which was likewise maintained at 80℃.
measurement was made at 25°C and a fixed angle of 90°.
Tween 80 (surfactant) and poloxamer 188 (co-surfactant) were
The PDI, another significant variable, describes the width
dissolved to make the aqueous phase and poured slowly to oil
or spread of the particle size distribution. The PDI value is
phase, O/W coarse emulsion was obtained which was further
between 0 and 1. PDI values less than 0.1 imply monodisperse
sonicated by probe sonicator (PCI analytics PVT Ltd PKS
particles and greater than 0.1 imply polydisperse particle size
750). Solid lipid nanoparticle dispersion was obtained which
distributions.7 Horiba SZ-100 was also used to assess PDI.
was stored at airtight container.
Zeta potential analysis
It is a measurement of the actual electric charge that is present
on nanoparticle surfaces. Zeta potentials with larger size
indicate more stable particles. The magnitude and sign of the
zeta potential can be used as an additional parameter to assess
surface chemical changes.8 We have diluted the zeta potential
of SLN loaded with T. chebuala with HORIBA SZ-100 with
Figure 1: Preparation method of SLN used in study double distilled water.

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 Nanoparticle Based Gel to Enhance Topical Delivery

Table 3: Optimization of TC loaded SLN in BBD with observed responses

Factor-1 Factor-2 Factor-3 Response-1 Response-2
Run
Amount of lipid (mg) Amount of surfactant (%w/v) Sonication time (min) Particle size (nm) Entrapment efficiency (%)
1 200 2 20 267 ± 1.3 67.32 + 1.21
2 150 3 10 244 ± 0.9 69.00 ± 1.09
3 150 2 15 295 ± 2.1 69.23 ± 1.9
4 150 2 15 296 ± 1.09 67.24 ± 2.1
5 150 1 20 331 ± 1.8 64.54 ± 1.7
6 100 2 20 271 ± 2.09 67.11 ± 2.01
7 150 1 10 329 ± 1.02 63.09 ± 2.07
8 100 2 10 340 ± 1.04 66.6 ± 2.4
9 200 3 15 215 ± 1.1 68.93 ± 1.20
10 200 1 15 254 ± 1.3 62.38 ± 1.32
11 150 3 20 201 ± 1.2 70.11 ± 1.01
12 200 2 10 221 ± 1.5 66.09 ± 1.29
13 150 2 15 295 ± 1.3 67.23 ± 2.1
14 150 2 15 283 ± 0.4 67.2 ± 2.12
15 100 1 15 343 ± 1.32 62.6 ± 1.21
16 100 3 15 215 ± 1.23 68.93 ± 1.3
17 150 2 15 296 ± 1.32 67.13 ± 1.7
Each value is reported as mean S.D. (n=3).

Determination of entrapment efficiency SLN’s) using a Cu K radiation source (λ = 0.15418 nm) at room
The entrapment efficiency of T. chebula in SLN was examined temperature. A voltage and current of 45 kV and 40 mA were
using dialysis. Two ends of a dialysis bag with the SLN used to scan at 2θ range 5°-90° 243.5
formulation (2 mLH) inside were knotted. The bag was Gel Preparation
submerged in 100 mL of a 30:70 methanol and distilled water The required amount of carbopol 934 was weighed out and
solution at 37.5°C and stirred using a magnetic mixer at 80 to mixed with a small amount of distilled water to make an
100 rpm. 5 mL of the sample was taken out of the beaker after aqueous dispersion. This mixture was hydrated for 4 to 6 hours
30 minutes, filtered and tested using a UV spectrophotometer to form SLN gel.11 40 mg drug of T. chebula dispersion was
at 280 nm (Shimadzu, UV-1800).9 The drug used for analysis added to SLN dispersion with propylene glycol 400, EDTA,
was expected to be free, and the formula below was used to methylparaben, and propylparaben. A mechanical stirrer
calculate the entrapment efficiency. running at 1200 rpm was used to add triethanolamine to the
aforementioned dispersion. Up till the carbopol was thoroughly
mixed, stirring was done. The gel was left to stand for the next
day to liberate any trapped air.
Scanning electron microscopy Characterization Study of Gel
Using a scanning electron microscope, the morphological Determination of physical appearance and homogeneity
characteristics of SLN were identified. The signal that reveals
Visual observation was done of the gel’s physical characteristics
details about the sample’s chemical composition and surface
and homogeneity.
morphology (texture).10 A single drop of the sample was
applied on a cover slip, and any extra moisture was dried out Determination of viscocity
at room temperature. At the Savitribai Phule Pune University The viscosity of the gel was measured using Brookfield
(SPPU’s) Central Instrumentation Facility (CIF), we have viscometer (Brookfield, RVDV pro II, USA) at 37℃ using
performed SEM. T-bar spindle with helipad attachment at 5, 10, 20, 50 and
X-ray diffraction 100 rpm.12
A German-made XRD called the Pan Analytical X’Pert Determination of pH
Pro model was used to measure the crystalline nature of the By placing the electrode in your sample and starting to read.
sample. The process was carried out on the sample (optimized Once your electrode has been inserted into the sample, hit the

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 Nanoparticle Based Gel to Enhance Topical Delivery

measure button and let the electrode sit in the sample for one made with a sterile cork borer or tip and a volume (20–100
to two minutes settle on a pH value. mL) of the solution at the required concentration. The prepared
Determination of Spreadability study of SLN gel gel sample and solid lipid nanoparticle were filled into bore at
37 ± 0.5°C for 48 hours under aerobic conditions. Following
Using a fabricated spreadability device, the gel’s spreadability
that, agar plates are incubated at the appropriate temperature
was assessed. Two glass slides of 7.5 x 2.5 cm each made up
based on the test microorganism. In the agar medium, the
the device. One glass slide was fastened to the wooden board,
antimicrobial agent (TC SLN dispersion and TC SLN gel)
and the other was mobile and attached to a thread that crossed a
diffuses and prevents the growth of the tested microbial strain.
pulley to support weight. The two glass slides were separated by
0.5 g of gel sample.12 In order to release the trapped air between The zone of inhibition was measured.17
the slides and create a homogenous gel coating, a 100 gm Stability Study
weight was kept on the upper slide and left there for one to In accordance with ICH recommendations, the optimized
two minutes. After the weight was removed, a 20 gm pull was formulation (SLN dispersion and TC-loaded SLN gel) was kept
applied to the top slide.13 The top slide’s travel time (in seconds) in a tightly closed container at 40 ± 2℃ and 75 ± 5% RH for
over a previously set distance was recorded. Following that, 3 months in a stability chamber that ICH verified. Change in
spreadability was examined using below formula: physical appearance, entrapment efficiency, particle size, and
S=M ease of redispersibility are examined for SLN dispersion and
change in physical appearance for TC-loaded SLN gel
Where S-spreadability, L-length of glass slide, t-time taken,
and M-weight which is tied on upper slide. RESULT AND DISCUSSION
Determination of Drug Content Solubility Study
By properly weighing a sample of gel (approximately 400 mg) The most important requirement for component screening is
and dissolving it in a little amount of water (about 100 mL), the the solubility of least soluble drugs. In solid lipid nanoparticle,
drug content of the gels was ascertained. Following that, the preservation of the drug in solubilized form depends on the
solutions were filtered and spectrophotometrically measured drug’s increased solubility in lipid. Based on solubility studies
at 280 nm.14 stearic acid was chosen as lipid matrix. Based on the stability
In-vitro drug diffusion SLN Based gel of dispersion surfactant and co-surfactant, Tween 80 and
poloxamer 188 were selected, respectively (Table 10).
Using modified Franz diffusion cells, in-vitro diffusion studies
were performed. These cells consist of an acceptor and Optimization and Validation
donor compartment, dialysis membrane 70, sample device, Maximum entrapment efficiency, physical formulation
magnetic stirring, donor compartment, and thermostatic stability, and a low particle size in the nanoscale range were
water bath. The releasing membrane’s surface area was the main factors for choosing an optimised batch. In order to
3.14 cm2. Approximately 45 mL of phosphate buffer saline verify the efficacy of the optimised formulation, a second batch
(PBS), pH 7.4, were used as the receptor compartment, of the identical composition with the predicted response was
which was agitated by a magnetic bar at 700 rpm to avoid prepared using the formulation with 136 mg of stearic acid,
concentration variations only in the donor medium and to 3% of tween 80 as a surfactant, and a 20-minute sonication
reduce stationary layers. In the donor compartment, each time. It was discovered that the experimental outcomes of the
SLN-based Gel had 1-mg of drug. The solution on the receptor optimised formulation were in good accordance with the value
compartment was kept at 37°C with a 0.5°C error throughout predicted (Figure 4, 5 and Table 3 to 6).
the testing. 5 mL of the sample solution was removed from
Independent Variables Effect on Particle Size
the receiving chamber after a predetermined time, and the
equal amounts of medium were added again.15 At 280 nm, the Given polynomial equation illustrates how a variable affects
samples were examined in triplicate spectrophotometrically. a particle:
Antimicrobial Study
Particle size (Y1) = +293.00-26.50*A-47.75*B-
Using the agar well diffusion method, the bactericidal 8.00C+22.25*AB+28.75*AC-11.25*BC-18.88*A²-17.38*B² +
activity of T. chebula gel and T. chebula loaded solid lipid 0.6250*C²
nanoparticles at the same concentration was determined
in-vitro. For Staphylococcus aureus and Escherichia coli, The coded equation can be used to calculate the relative
respectively, nutrient agar and MacConkey agar are utilized. significance of the components by comparing the factor
In an autoclave, the medium was prepared and sterilised for coefficients. According to the equation above, the amount
20 minutes at 121°C.16 Sterilized media were added to sterile of lipid (F-value - 65.65) has a less significant impact than
petri plates and given time to set up aseptically. The microbial surfactant concentration (F-value -213.16) and sonication
inoculum on the agar plate inoculated the topmost layer. The time (F-value -5.98). Particle size decreases when independent
antimicrobial extract solution (SLN dispersion and gel) is then variables like lipid amount, surfactant concentration, and
added to the well after a 6 mm-diameter hole is aseptically sonication time increase. Particle size changes when two

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A B
Figure 3: Solubility of drug in lipid (mg/mL)

variables are changed at once. The interaction terms AB, AC

and BC and squared terms A2, B2 and C2 show this. When
the lipid content increases while the surfactant concentration
remains constant, the particle size increases because there
isn’t enough surfactant. As a result, the surfactant’s ability to
emulsify becomes less effective, leading to increased particle C D
size and particle aggregation. A smaller emulsion droplet is
formed when the interfacial tension between the aqueous and
lipid phases is effectively reduced as a result of a high surfactant
concentration. An optimum concentration of surfactant is
desired to effectively stabilize the SLN particles by preventing
particle aggregation. Particle-particle interactions are caused
by sonication because the system’s higher kinetic energy results
in smaller particles. Figure 4 shows 3D design of an optimized E F
batch that illustrates how different variables affect particle size.
Independent Variables Effect on %Entrapment efficiency
The entrapment efficiency of the various batches ranged from
62.60 to 70.11%. Higher entrapment efficiency is preferred
for the best possible drug delivery to the target site. The
polynomial equation below shows how the variable affects
entrapment efficacy: G H

Entrapment Efficiency (Y2) = +67.61- 0.0487* A +

3.03*B + 0.5375*C + 0.0875* AB + 0.1800* AC- 0.0850*
BC- 0.9168* A²-1.01*B²+ 0.0908*C²

According to the aforementioned equation, the amount of

lipid ratio (f-value of 0.8529) negatively impacts entrapment’s
effectiveness. Due to the average space being available for I J
drug entrapment into the lipid matrix, the SLN’s entrapment
efficiency improves as lipid concentration falls. According to the
equation, the surfactant had a favorable impact on entrapment
effectiveness (F-value of 142.88), although its overall impact
was biphasic. Due to the drug’s increased solubility in readily
available lipid and the decrease in drug partition in the aqueous
phase, the initial rise in surfactant concentration results in
an improvement of entrapment efficiency. The efficiency of K L
entrapment was positively impacted by sonication time. Figure Figure 4: A,C,E,G,I,K -3D response plot B,D,F,H,I,J- Contour plot
4 shows 3D design of an optimized batch that illustrates how of depicting the effect of concentration of surfactant, amount of lipid
different variables affect entrapment efficiency. and Sonication time on Particle size and % Entrapment efficiency
respectively
Evaluation of Optimized Formulation
polydispersity index, which was found to be 0.342, indicates
Particle size that the particle distribution is polydisperse. Particle sizes for
Dynamic light scattering (DLS) analysis was used to determine batches B1 through B17 range from 101 to 395 nm. According
the SLN particle size (HORIBA SZ-100). Figure 6. shows to Figure 6, the particle size of the optimized batch was
the particle size distribution of the optimized SLN. The discovered to be 201 nm.

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Table 3: Fit Statistic of Quadratic Model

(Quadratic Model) R2 Adjusted R2 Predicted R2 Inference
Particle Size 0.9822 0.9594 0.7696 The Predicted R2 - 0.7696 and the Adjusted R2 - 0.9594 are reasonably in
agreement i.e., difference <0.2.
Entrapment Efficiency 0.9590 0.9064 0.8881 The Predicted R2 - 0.8881 and the Adjusted R2 - 0.9064 are reasonably in
(%) agreement i.e., difference <0.2.
R2 = Regression value
Table 4: Result of ANOVA of quadratic model for solid lipid
nanoparticle
R1 R2
Response
Particle size Entrapment Efficiency%
Model Quadratic Quadratic
Model Model
Some of square 33096.06 88.11
Degrees of freedom 9 9
Mean squares 3677.34 9.79
F-Value 3.95 11.74
P-value (prob>F) 0.0420 0.0019
Significant Significant
R2 value 0.9822 0.9836
Lack of fit
0.0769 0.21
F-Value
Figure 7: Zeta potential analysis of optimized formulation
Lack of Fit P value 0.3592 0.8820
(Non- Significant) (Non- Significant)
Zeta potential
Understanding the stability of nanoparticles in aqueous
solutions requires understanding the surface charge potential,
which is indicated by the zeta potential. The SLN’s zeta
potential was found to be -20.4 mv. It was claimed that the
surface of the synthesized nanoparticles was negatively
charged. By bringing the same charges together, the positive
or negative charge on a nanoparticle’s surface gives it stability
and prevents it from aggregating (Figure 7).
Entrapment efficiency (%)
Figure 5: Desirability plot for the software generated solution. To deliver the ideal dose of drug to the target site, entrapment
Desirability value is 1 which validates the optimized model and process. efficiency is desired. The amount of surfactant and the duration
of the sonication had a significant effect on the entrapment
efficiency. Entrapment efficiency for the improved batch was
determined to be 70.11%, indicating that the drug is trapped
inside the lipid matrix.
Scanning electron microscopy
FESEM images clearly show the presence of synthesized
nanoparticles. The nanoparticles are spherical in shape.
Nanoparticles are aggregated due to the spreading and drying
technique on coverslip and few individual particles are
observed. The synthesized nanoparticle is in range of 140.8
Figure 6: Particle size analysis (optimized batch) to 192.8 nm (Optimized Batch)
Table 5 : Selected optimized batch
Concentration of Entrap-
Sr.No Amount of lipid Sonication Time Particle size Desirability Inference
surfactant ment Efficiency
1 136.00 3.000 20.000 201.25 70.03 1.000 Selected

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Table 6: Predicted and actual values of optimized batch by design

expert software
Response Predicted values Observed values
Particle Size 201.00 201
Entrapment efficiency (%) 70.03 70.11

X-Ray Diffractometry
X intercept Y count
20.054 234.705
20.034 233.105
Powder diffraction experiments were performed to further
study the interactions between the components of the
formulations principle peaks of T. chebula loaded SLN was
observed at 2θ angle 20.054, 20.034, 21.188, indicating the
amorphous nature of the drug, it is due to we don’t get a sharp
peak. SLN has a complex lipid and drug structure mixture, Figure 8: FE-SEM images of solid lipid nanoparticle
and we have successfully synthesized SLN.
Evaluation of T. chebula-loaded Solid Lipid
Nanoparticle-Based Gel
Appearance and clarity
The SLN formulation is faint brown and translucent
Drug content and pH
Drug content of T. chebula-loaded SLN gel was found to be
86.92 ± 0.55%.
Viscosity
Observed viscosities at 100, 50, 20,10,5 RPM are shown in
Table 7 & Figure 10.
Spreadability Figure 9: X-Ray Diffraction pattern of T. chebula loaded SLN

The spreadability of the synthesized SLN gel formulation

Table 7: Viscosity of SLN gel formulation
was determined to be 12.48 0.29 gcm/sec, indicating easy
spreadability. The produced gel’s thickness and spreading rpm SLN gel
time were inversely related to the gel’s spreadability. Good 100 17200 ± 121
spreadability is preferred to apply the antibacterial gel to the 50 23600 ± 2.11
affected area and ensure patient compliance.
20 28000 ± 2.09
In-vitro drug diffusion study
10 35530 ± 1.82
The immediate drug release from the SLN gel formulation
5 51390 ± 2.32
was higher because there was more unentrapped drug in the
SLN dispersion and more drug on the SLN’s outermost shell. Each value is reported as mean S.D. (n=3).
After the initial burst, it was discovered that the drug release
was sustained, releasing 92 ± 98% of T. chebula in T. chebula
in 8 hours. Terminalia chebula is trapped in SLN and then
diffused in a viscous gel matrix in SLN gel. As a result, SLN
gel provides two barriers, SLN matrix and gel matrix for
drug release by diffusion, maintaining the release of the drug
(Table 8 and Figure 10).
Antimicrobial study
The T. chebula-loaded solid lipid nanoparticle showed
significant effect on microbes S. aureus and E. coli having zone
of inhibition 18.9 ± 0.18 mm and 19.7 ± 0.21 mm, respectively
(Table 9 and Figure 11, 12). The zone of inhibition of S. aureus Figure 10: Viscocity of SLN gel

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Table 8: Drug release through dialysis membrane of T. chebula-loaded

SLN gel
TC loaded TC loaded SLN
Formulation Time
SLN gel dispersion
TC loaded 0 minutes 0 0
solid lipid
15 minutes 33.43 ± 2.12 41.58 ± 1.3
nanoparticle
gel 30 minutes 64.5 ± 2.01 75.53 ± 1.43
60 minutes 75.31 ± 2.13 83.71 ± 1.32
120 minutes 81.74 ± 2.11 89.54 ± 1.23
240 minutes 84.81 ± 1.02 93.36 ± 2.12
480 minutes 89.24 ± 1.09 96.79 ± 2.32
Each value is reported as mean S.D. (n=3)

Table 9: Zone of Inhibition shown by T. chebula-loaded SLN and gel

Zone of inhibition
S.No Formulation Figure 12: Zone of inhibition shown by A. Control B. SLN dispersion
E. coli S. aureus C. SLN gel for E.coli
1 A. SLN Dispersion 18.9 ± 0.18 mm 19.7 ± 0.21 mm
2 B. T. chebula loaded 15.6 ± 0.25 mm 17.7 ± 0.17 mm
SLN gel
3 C. Control nil nil
Each value is reported as mean S.D. (n=3)

Figure 13: Zone of inhibition shown by A. Control B. SLN dispersion

Figure 11: In-vitro Drug Release of T. chebula-loaded SLN gel C. SLN gel for S. aureus

Table 10: Accelerated stability study as per ICH Guideline

Time in months Evaluation parameters (40 ± 2°C and 75 ± 5%RH)
Change In Physical Change in Physical
Entrapment efficiency Particle Size Ease of Redispersibility
appearance Appearance
TC loaded SLN TC loaded SLN TC loaded SLN TC loaded SLN TC loaded SLN gel
0 month No 70.11 ± 0.23% 201 ± 0.06 nm + No
1st month No 69.59 ± 0.29% 204 ± 0.5 nm + No
2nd month No 69.09 ± 0.46% 212 ± 0.67nm + No
3rd month No 68.79 ± 0.32% 219 ± 0.74 nm + No

and e. coli by T. chebula-loaded SLN-based gel were found in physical appearance, entrapment efficiency, particle size,
15.6 ± 0.25 and 17.7 ± 0.17 mm, respectively. and ease of re-dispersibility.
The result indicate that the SLN formulation has better CONCLUSION
antimicrobial effect against many causative agents reported
The current study is carried out for determining the rationality
Stability study of phytopharmaceutical T. chebula-loaded SLN gel as an
The result of stability study shows that TC-loaded SLN antibacterial agent. The optimized SLN formulation, which
dispersion and TC-loaded SLN gel did not show major changes contains tween 80 and stearic acid, exhibits low particle

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size, high drug entrapment, and sustained drug release. concentration on zeta-potential measurement results and
This study’s findings demonstrated that plants contain reproducibility. Particuology. 2010 Jun 1;8(3):279-85.
bioactive compounds, which are associated with antibacterial 8. Honary S, Zahir F. Effect of zeta potential on the properties of
characteristics in plants. T. chebula gel shows a significant nano-drug delivery systems-a review (Part 2). Tropical journal
antibacterial effect against causative pathogens like S. aureus, of pharmaceutical research. 2013 May 9;12(2):265-73.
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IJDDT, Volume 13 Issue 2, April - June 2023 Page 482