Gel formulation and characterization of drug

X and evaluation of its anti-psoriatic activity.

Priyanka
M. Pharm Sem. III student
School of Pharmaceutical Sciences,
Delhi Pharmaceutical Sciences and Research University,
New Delhi

Under the guidance of

Dr. Amit Awasthi Dr. Mukesh Nandave

Associate Professor of Immunology Associate Professor of Pharmacology
Translational Health Science and Technology Institute, School of Pharmaceutical Sciences
Faridabad Delhi Pharmaceutical Sciences and Research University,
New Delhi

1
 Contents

• Background

• Diagnosis and treatment available

• Rationale

• Objectives

• Materials and methods

• Work to be done

• Bibliography
2
 Immunological disorders

An immune disorder is due to deficiency or overactivity of

immune components.

• Rheumatoid Arthritis
• Multiple Sclerosis
• Psoriasis
• Lupus Erythematosus
• Type 1 Diabetes
• Alopecia
• SCID
• AIDS

3
 Background

 Autoimmune disease

 T-cell mediated

 WHO report

 Mild to severe

 More prone in male

4
Psoriasis Pathogenesis

IL-17

5
What, Who and How of the Disease

6
Diagnosis

7
Treatment available

8
 Rationale

Psoriasis is skin ailment and topical application of drugs are

desired. Drug X has a very high anti-psoriatic activity in our
settings, but it is a highly lipid soluble drug. Therefore, a
pharmaceutical formulation for the sustain release of drug X
is required to get the amelioration from the disease.

9
 Objectives

• To prepare gel formulation of drug

X.

• To characterize the gel formulation

of drug X.

• To evaluate the Anti-psoriatic

activity of gel formulation of drug X

10
 Prevent first
pass
metabolism
Efficacious
with no Prevent GIT
disturbance
irritation

Gel
formulation
Less greasy,
More
High drug
stability
loading

Easily
spreadable,e
mollient
For gel formulation: Result
• Carbopol-940
• Tween-80
• Glycerol Anhydrate
• Drug X
Gel formulation methodology
• Triethanolamine
• Distilled water
Tween 80 Glycerol Distilled Water

Magnetic stirring (2000-5000 rpm) at RT

Add API
Magnetic stirring (2000-5000 rpm) at RT

Add carbopol-940
Incubation for 4-24 h at RT for dispersion

Neutralization

Gel formulation

Fig. Methodology for gel formulation. Schematic representation of methodology followed

for gel formulation shown as flow chart. The final volume of each formulation was kept as
100ml.

12
 Effect of neutralizer in gel formulation

A) B)

F1 F6 F1 F6

pH value: 3-5 (Before TEA Addition) pH value: 6-8 (After TEA Addition)

13
 F1 F2 F3 F4 F5 F6 F7 F8 F9 F10

F1-F5 with 1 mg drug F6-F10 with 10 mg drug

Figure. Image for homogeneity and appearance of different gel formulations of drug X. The
formulations containing different doses of drug X was taken by putting 20ml of gel in 50ml
Falcon (as shown). Formulations F1-F5 has 1mg of drug X & formulations F6-F10 has 10 mg of
drug X. These formulations were prepared with different proportions of tween-80 :glycerol
anhydride (1:1 for F1 & F6, 1:2 for F2 & F7, 1:3 for F3 &F8, 1:4 for F4 & F8 and 1:5 for F5 &
F10).
 Ingredients
(For total volume of 100 ml)
Formulations
Tween Glycerol Drug Carbopol-940 TEA (ml)
80 (ml) (ml) (mg) (w/v)
F1 1 1 1 1.5 0.5

F2 1 2 1 1.5 0.5

F3 1 3 1 1.5 0.5

F4 1 4 1 1.5 0.5

F5 1 5 1 1.5 0.5

F6 1 1 5 1.5 0.5

F7 1 2 5 1.5 0.5

F8 1 3 5 1.5 0.5

F9 1 4 5 1.5 0.5

F10 1 5 5 1.5 0.5

Table 1. Tubular representation of the amount of components used for

different gel formulations.
 A. pH (Before pH (After
Formulation
neutralization) neutralization)
F1 4.33 6.63
F2 4.84 6.57
F3 5.09 6.6
F4 4.99 6.68
F5 5.35 6.94
F6 4.26 6.65
F7 4.44 6.78
F8 5.06 6.89
F9 4.98 6.76
F10 5.25 6.98

pH (Before neutralization)
B.
pH (After neutralization)
8
7
pH value

6
5
4
3
2
1
0
F1 F2 F3 F4 F5 F6 F7 F8 F9 F10

Gel formulations

Figure. pH evaluation of different gel formulations of drug X before and after TEA
neutralization. 1 gm of different gel formulations was completely dissolved in 100 ml of milliQ water
through vigorous stirring thereafter, pH of different formulation was evaluated by using pH meter.
 Characterization

• pH: 6 to 8

• Grittiness: Free from fine or particulate matter

• Homogeneity and appearance: Transparent

• Stability: Stable at 37˚ C but still we would check the release

pattern

• Skin-irritation: No

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 Formulations Grittiness Homogeneity Appearance Skin-irritation

F1 No *** Transparent No

F2 No *** Transparent No

F3 No *** Transparent No

F4 No ** Transparent Slight irritation

F5 No ** Transparent Slight irritation

F6 No *** Transparent No

F7 No *** Transparent No

F8 No *** Transparent No

F9 No ** Transparent Slight irritation

F10 No ** Transparent Slight irritation

Table 2: Tubular representation of gel characterization of gel formulations. Table showing gel
characterization parameters of grittiness, homogeneity, appearance and skin-irritation for different gel
formulations of drug X. *** for the best gel homogeneity and ** for the gel homogeneity.
 Psoriasis Animal Model
• Imiquimod gel
(Glenmark)
• Ketamine and
xylamine injection
• Lubic gel (Neon)
C57BL/6 mouse
(n= 15)
Approach -I
Approach -II

Remove the hairs from Apply the Lubic gel on

back of the mice (n= 9) right ear pinna and
Imiquimod cream on the
left ear pinna of the same
animal (n=6)

Apply the Apply the

Lubic gel (Neon) Imiquimod cream (Glenmark)
(n= 3) (n= 6)

Follow them for the 7-8 days for the

Follow them for the 7-8 days for the symptoms appearance of the disease
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symptoms of the disease
A. Group Left Ear Right Ear
Group A Control Control+Drug X (1μM)
Group B IMQ IMQ+Drug X (100nM)
Group C IMQ IMQ+Drug X(1μM)

Topical application of IMQ and or drug

B.

Day 0 1 2 3 4 5 6

Figure. Experimental protocol for grouping of animals, indication of timeline and

application of IMQ and gel formulation. In the 6 days experimental timeline, the disease
and treatment were given to consecutive 5 days. The body weight, erythema, scaling and
ear thickness were measured from day 0- day 6 to compare the efficacy of formulations F1
containing drug X (100nM) & F6 containing drug X (1μM).
 Control IMQ

Figure. Images of mouse ear pinna with or without IMQ application. Images of mouse
ear pinna of control vs topical IMQ application respectively.
 Control F1 F6

Figure. Images of mouse ear pinna with or without gel formulations. Images of mouse
ear pinna taken with topically applied F1 or F6 or without treatment.
 Work to be done

• Use the psoriasis model available in SAF at THSTI and apply the gel
formulation on the ear pinna of the mice.

• Evaluate the efficacy of the formulations of drug X.

• Histopathological study of ear.

• Also compare the efficacy of our formulation with the already

available formulations in the market by the different pharmaceutical
companies .

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 Bibliography

• Abu, H., II, N. F. Abo El-Magd, A. R. El-Sheakh, M. F. Hamed and A. E. H. Abd El-Gawad (2018). "Pivotal role
of Acitretin nanovesicular gel for effective treatment of psoriasis: ex vivo-in vivo evaluation study." Int J
Nanomedicine 13: 1059-1079. Alemdaroğlu, C., Z. Değim, N. Çelebi, F. Zor, S. Öztürk and D. Erdoğan (2006).
"An investigation on burn wound healing in rats with chitosan gel formulation containing epidermal growth
factor." Burns 32(3): 319-327.
• Chawla, V. and S. A. Saraf (2012). "Rheological studies on solid lipid nanoparticle based carbopol gels of
aceclofenac." Colloids and Surfaces B: Biointerfaces 92: 293-298.
• Ma, H. Q., Y. Wang, Y. H. Mao, S. Y. Wang, Y. P. Zhang, C. Q. Zuo, L. Shao-Juan and J. W. Liu (2018). "The
inactivation of the non-enveloped enterovirus 71 (EV71) by a novel disinfectant gel formulation for topical use."
Drug Dev Ind Pharm: 1.
• Raghuwanshi, N., T. C. Yadav, A. K. Srivastava, U. Raj, P. Varadwaj and V. Pruthi (2019). "Structure-based drug
designing and identification of Woodfordia fruticosa inhibitors targeted against heat shock protein (HSP70-1) as
suppressor for Imiquimod-induced psoriasis like skin inflammation in mice model." Mater Sci Eng C Mater Biol
Appl 95: 57-71.
• Weber, E., M. Moyers-González and T. I. Burghelea (2012). "Thermorheological properties of a Carbopol gel
under shear." Journal of Non-Newtonian Fluid Mechanics 183-184: 14-24
• Kaur, N., K. Sharma and N. Bedi (2018). "Topical Nanostructured Lipid Carrier Based Hydrogel of Mometasone
Furoate for the Treatment of Psoriasis." Pharm Nanotechnol 6(2): 133-143.
• Kawai, T. and H. L. Malech (2009). "WHIM syndrome: congenital immune deficiency disease." Curr Opin
Hematol 16(1): 20-26.

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 Bibliography

• Ali, J., N. Akhtar, Y. Sultana, S. Baboota and A. Ahuja (2008). "Antipsoriatic microemulsion gel formulations for
topical drug delivery of babchi oil (Psoralea corylifolia)." Methods Find Exp Clin Pharmacol 30(4): 277-285.
• Martens-Lobenhoffer, J., M. Rinke, D. Losche and H. Gollnick (1999). "Long-term stability of 8-
methoxypsoralen in ointments for topical PUVA therapy ('Cream-PUVA')." Skin Pharmacol Appl Skin Physiol
12(5): 266-270.
• Kim, C. H., J. K. Yoo, S. H. Jeon, C. Y. Lim, J. H. Lee, D. B. Koo and M. Y. Park (2018). "Anti-psoriatic effect
of myeloid-derived suppressor cells on imiquimod-induced skin inflammation in mice." Scand J Immunol:
e12742.
• Li, Y., G. Zhang, M. Chen, M. Tong, M. Zhao, F. Tang, R. Xiao and H. Wen (2019). "Rutaecarpine inhibited
imiquimod-induced psoriasis-like dermatitis via inhibiting the NF-kappaB and TLR7 pathways in mice."
Biomed Pharmacother 109: 1876-1883.

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