Therapeutic Evaluation of 5% Topical Amlexanox Paste and 2% Curcumin Oral Gel in the Management of Recurrent Aphthous Stomatitis‑ A Randomized Clinical Trial

1. Therapeutic Evaluation of 5% Topical
Amlexanox Paste and 2% Curcumin Oral Gel
in the Management of Recurrent Aphthous
Stomatitis- A Randomized Clinical Trial
Gauthaman J, Ganesan A. Therapeutic evaluation of 5% topical amlexanox paste and 2% curcumin oral gel
in the management of recurrent aphthous stomatitis- a randomized clinical trial. J Indian Acad Oral Med
Radiol 2022;34:17-21.
Presented By –Zareesh Akhtar
Department of Oral medicine and radiology

2. INTRODUCTION
• The term “aphthae” originated from the Greek word
“aphthi” which means “to set on fire” or “to inflame”
coined by the Greek philosopher, Hippocrates.
• The RAS occur as shallow ulcers with well-defined
erythematous margins with a pseudomembranous crater.
There are three clinical types of RAS namely;
1. major aphthae affecting 10% of the population,
2. minor RAS affecting >70%, and
3. herpetiform ulcers affect around 10% of the population.

3. • Recurrent aphthous stomatitis(RAS) is a
common oral mucosal condition that has
multifactorial etiology.
• They are recurrent and also known as
“canker sores.”
• They appear as recurrent, multiple, small,
round, or ovoid ulcers, with circumscribed
margins, having yellow or gray floors, and
are surrounded by erythematous haloes.
• The global incidence of aphthous ulcers was
found to be 20% and prevalence of 21.7% in
a nationwide survey conducted in 2010–
2012 in India

4. • Characterized by intense pain and discomfort, crippling normal
activities such as chewing and swallowing.
• A condition of multifactorial nature, several etiologies such as
local trauma, psychological stress, allergy to products
containing sodium lauryl sulfate (oral care products such as
toothpaste)
• Hormonal fluctuations such as ovulation, menstruation in
women, and alterations in oral microbial flora have been
related to the occurrence of RAS.

5. • It has been linked to systemic conditions like malabsorption,
enteropathy, celiac disease, hematinic deficiencies(iron, folate,
vitamin B6, and B12), and vitamin D, zinc, and thiamine-
related deficiencies.
• Several therapeutic modalities including topical anesthetics,
antibiotics, corticosteroids, nutritional supplements, immune-
modulatory drugs, laser therapy, and combination therapies
have been in vogue

6. • Amlexanox (C16H14N204), a topical anti-inflammatory and
anti-allergic drug is the only clinically proven drug approved
by the US Food and Drug Administration for the management
of RAS.
• It inhibits the formation and release of histamine and
leukotrienes from mast cells, neutrophils, and mononuclear
cells

7. • Curcuma longa is a potent herbal counterpart that has been evaluated
for its anti-inflammatory and anti-oxidant effects in many oral
diseases as an alternative to corticosteroids.
Curcumin: An Anti-Inflammatory Molecule from a Curry Spice on the Path to Cancer Treatment,Molecules 2011, 16, 4567-4598.

8. • Curcumin is a phytochemical that is obtained from the plant,
C. longa, which belongs to the family Zingiberaceae.
• It has been used in Indian traditional medicinal practices.
• It is a potent anti-inflammatory and anti-oxidant that is being
explored in several clinical trials for its innumerable benefits.
• Apart from curcumin, the other essential compounds present in
it are dimethoxy curcumin and bisdemethoxycurcumin.

9. AIM
• The primary objective of the study was to compare the efficacy
of 5% topical amlexanox and 2% topical curcumin in the
management of RAS (minor).
• The second objective was to evaluate the recurrence rate of
RAS (minor) over 6 months.

10. MATERIALAND METHOD
• The present study was a single-blinded interventional
randomized clinical trial conducted in the outpatient
department.
• The ethical approval was obtained from the Institutional Ethics
Committee, Madha Dental College & Hospital, Kundrathur,
Chennai (MDCH/MDS/EC/-026) dated May 12, 2019.
• The study was designed and conducted according to the
CONSORT guidelines (2010) for randomized clinical trials.

11. • Prior informed consent was obtained in written form from all
participants of the study.
• A total of 48 participants were included in the randomized
clinical trial.
• They were divided into two study groups: Group A received
5% amlexanox oral paste and Group B received 2% curcumin
oral gel.
• Randomization was done using computer-generated sequence
numbers.

12. INCLUSION CRITERIA
• Age group: 18–30 years
• Participants giving a history of RAS minor (ulcers that
measure <10 mm,
• and heal within 4–14 days without scarring) with a
minimum of two episodes in a year
• Participants with 1–3 minor RAS of less than 48 h
duration.

13. EXCLUSION CRITERIA
• Participants with any systemic disorders
• Pregnant, lactating women
• Participants with the habit of smoking or alcoholism
• Participants undergoing orthodontic therapy
• Participants who had undergone tooth extraction or any dental
surgical procedure in the past 2 weeks
• Participants under any Non-steroidal anti-inflammatory drugs
(NSAIDS)/systemic steroids/immune suppressant drugs
• Participants are allergic to medicines or foods.

14. • A detailed oral examination was done for all 48 participants and
all baseline parameters such as the site, size, number, pain,
erythema, and exudation were recorded on the first day
• Topical 5% amlexanox ointment (amlenox oral paste containing
5% amlexanox, Zuventus laboratories) and
• 2% curcumin oral gel(curenext oral gel containing 10 mg
Curcuma longa extract and colors such as erythrosine from
Abbott pharmaceuticals)
• were randomly packed in identical packages and allotted to the
participants, not aware of the drug

15. • Group A participants were instructed to take ¼ inch (0.5
cm) of the paste approximately and apply it at the site of the
lesion.
• Group B participants were asked to apply a very little
amount of the gel just enough to form a thin smear over the
lesions.
• Both groups were asked to apply the drug four times a day;
in the morning after performing oral hygiene, after lunch,
after dinner, and before going to bed.

16. • The maximum diameter of the ulcers was measured with
William’s calibrated periodontal probe on days 1, 4, and 7.
• For assessing pain, a Visual Analog Scale (VAS) used
• The degree of erythema was evaluated with a 4-point scale
(modified Greer et al. scale)in which
-“0” referred to no erythema
-“1” denoted light red/pink color
-“2” denoted red but not dark in color, and
-“3” referred to a very red, dark color.

17. DATAANALYSIS
• All data were analyzed using SPSS version 22.
• An independent t-test with Welch’s correction of variance was
done for both groups.
• The intergroup comparison and intragroup comparisons for
non-categorical data on days 1, 4, and 7 were done using the
Chi-square test.
• P value of ≤ 0.05 was considered significant.

18. RESULT
• Forty-eight participants were included in the present study of which,
18 were male and 30 participants were female.
• The mean ulcer size on days 1, 4, and 7 in Group B participants were
more when compared to Group A participants

19. • The mean erythema
levels on day 1 for Group
A and Group B were 1.75
and 1.58 respectively.
• The erythema levels on
days 3 and 7 were 1.42
and 0.58 for Group A and
1.23 and 0.27 for Group
B, respectively

20. • The mean pain scores measured on days 1, 3, and 7 were lower in
Group B participants when compared to Group A participants
• When the participants were checked for recurrence, those who
used amlexanox had a high recurrence rate (92%) when compared
to those who used curcumin (50%)

21. DISCUSSION
• In the present study, 18 participants were male (37.5%) and 30
participants were female (62.5%), which shows a female
predominance (1:1.7) similar to previous studies.
• The average age of the participants was 22.5 years a

22. • The most common site of the minor aphthous ulcers was
the lower labial mucosa (47%), followed by the upper
labial mucosa (21%), tongue (16%), buccal mucosa (11%),
and the floor of the mouth (5%).
• A predominance of RAS among female participants
occurred in the lower labial mucosa (61%), similar to that
reported in the study by Raman and Pitty.

23. • The erythema on day 3 was reduced in group B participants
when compared to group A participants.
• On day 7, there was a significant reduction in erythema in
participants using curcumin oral gel compared to those who
used amlexanox (p = 0.041).
• Pain scores were also less on day 4 in the curcumin using
group when compared with group A.
• Also, the pain score reduced significantly on day 7 in
curcumin-using patients when compared with amlexanox

24. • Curcumin performed better in reducing the erythema and
significant pain relief was noted on day 7 among the group B
participants.
• In present study there was a 37% reduction in pain on day 3 in
group A and a 42% reduction in pain in group B.
• On day 5, there was a 46% in groupA participants and a 60%
reduction in pain in group B.
• On day 7, there was 88% in group A and 98% pain reduction in
group B participants.

25. • When the size of the ulcers was measured, both groups showed a
decrease in the size from day 1 to day 7.
• Although there was no significance, the group that used
amlexanox performed well in reducing the ulcer size with a
mean size of 3.2 on day 1, 2.63 on day 3, and 1.0 (mm) on day 7.
• The results were consistent with those of various studies that
used amlexanox where the application of amlexanox in the pre-
ulcerative stage reduced the ulcer size significantly by the third
day itself.
• Curcumin showed a mean ulcer size of 3.88 on day 1, 2.71 on
day 3, and 1.25 on day 7.

26. • Curcumin was found to be significantly effective in the
reduction of recurrence rates when the participants were
reviewed on days 30, 60, 90, and 180.
• Only 1 participant reported recurrence on day 30 in Group
B, 29.16% (7 participants) on day 60, 37.5% (9
participants) on day 90, and 50% (12 participants)
reported recurrence at the end period of 6 months.

27. CONCLUSION
• The present study suggests that curcumin can be used as a
potential substitute to other drug therapies in the management
of RAS minor as it is effective in reducing erythema, pain, and
also recurrence of ulcers.
• Similar herbal alternatives with reduced adverse effects have to
be considered in such recurrent oral diseases for a better
prognosis.

28. CROSS REFERENCES

29. 1-An Evaluation of the Efficacy of Amlexanox and
Triamcinolone Topical Paste in the Treatment of
Recurrent Aphthous Stomatitis
Altaf Hussain Chalkoo, Bashir Ahmad Wani, Prenika Sharma, Tauseefa Jan. An
evaluation of the efficacy of amlexanox and triamcinolone topical paste in the
treatment of recurrent aphthous stomatitis. International Journal of Contemporary
Medical Research 2018;5(9):I20-I22.

30. AIM AND OBJECTIVE -was to evaluate the effectiveness
of Amlexanox 5% and Triamcinolone 0.1% for the treatment
of recurrent aphthous ulcers.
MATERIAL AND METHODS
• This double-blinded randomized clinical study includes 36
patients suffering from recurrent aphthous ulcers
• Aged between 25 and 55 years old and, having minor
aphthous ulcers not more than 48 hours old.

31. • Group-1 was administered Triamcinolone 0.1%
(Kenocort 0.1% oral paste, Abbort Lab), while
• Group-2 was administered Amlexanox 5% (Lexanox
5% oral paste, macleods Pharma India).
• The patients used these pastes four times daily for 7
days.
• The patients were followed at days 0, 3, 5 and 7 and
scores were assessed using visual analog scale.

32. RESULTS
The results showed that in both of the groups, there was reduction
of pain and ulcer size significantly at subsequent follow up visits at
3rd, 5th and 7th days (p< 0.01).
None of the patients reported with pain in both the groups on 7th
day of treatment. No significant difference was noted between both
for their efficacy on pain relieving as well as on tingling in the
present study
CONCLUSION
This study showed that both Amlexanox and Triamcinolone are
active treatment options for RAS with no statistically significant
difference between both with regards to pain, tingling and ulcer
size reduction.

33. 2-Topical Curcumin and Triamcinolone
Acetonide in Recurrent Minor Aphthous
Ulcers: A Pilot Trial
Raman P, Pitty R, Krithika CL, et al. Topical Curcumin and
Triamcinolone Acetonide in Recurrent Minor Aphthous
Ulcers: A Pilot Trial. J Contemp Dent Pract 2020;21(8): 884–
890.

34. AIM AND OBJECTIVE :
• To evaluate the efficacy of topical curcumin and topical
triamcinolone acetonide in a professional population with
minor aphthous ulcers by assessing six clinical variables: site,
size, pain, healing period, frequency of recurrence and number
of ulcers.
MATERIAL AND METHODS :
• This randomized, parallel designed pilot trial was performed
on 60 symptomatic individuals with minor aphthous ulcer.

35. • Allocated randomly into group I and group II.
• Participants in group I were treated with topical curcumin and
• group II were treated with topical triamcinolone acetonide for
a period of 6 months.
• All participants were blinded to the drug they received.
• Participants were assessed on day 1, day 3, day 5, day 7, and
after healing for symptomatic reduction in pain, size, healing
period, frequency of recurrence, and in the number of ulcers.

36. RESULT
CONCLUSION
• Lower labial mucosa was found to be predominant site of minor
aphthous ulcer in both the groups.
• A gradual reduction in pain and size was noted in both the groups
with statistical significance of p value 0.05.
• Study showed clinically beneficial effects with topical curcumin
with regard to ulcer size, pain, healing, and recurrence rate.
• Also topical curcumin gel was well tolerated and topical
triamcinolone acetonide oral paste with a borderline favorable
result.

37. 3-Comparative Evaluation of the Efficacy of Topical
Amlexanox 5% Oral Paste and Triamcinolone
Acetonide 0.1% Oral Paste in the Treatment of
Recurrent Aphthous Stomatitis (RAS)
Shrivastava K, Naidu G, Deshpande A, Handa H, Raghuvanshi V,
Gupta M. Comparative evaluation of the efficacy of topical amlexanox
5% oral paste and triamcinolone acetonide 0.1% oral paste in the
treatment of Recurrent Aphthous Stomatitis (RAS). J Indian Acad Oral
Med Radiol 2018;30:235-40.

38. AIM AND OBJECTIVE –
To compare the clinical efficacy of topical triamcinolone
acetonide 0.1% and amlexanox 5% in recurrent apthous
stomatitis(minor).
MATERIAL AND METHODS
Forty adult patients were assessed for erythema, ulcer size, pain
scores, and ulcer healing on three evaluation visits within 24 h of
ulcer formation, third day, and fifth day.
All participants were monitored for compliance with treatment
protocols of four times daily application of calibrated quantity of
medication.

39. Result –
-Ninety percent of controls when compared with 65% of the
participants in the amlexanox group showed complete
improvement of peri-ulcer erythema.
-Pain reduction was marked from the first to the fifth day.
-The control participants showed 90% reduction in pain in
comparison to 70% in the amlexanox group.
-The mean ulcer size was shown to reduce from the first to fifth
day in both groups
-Completely healed ulcers were seen in 70% of participants in
control group compared with 75% of participants in the amlexanox
group.

40. CONCLUSION
• The data suggest that the clinical efficacy of topical amlexanox
5% is comparable to topical 0.1% triamcinolone acetonide and
may be considered a substitute except in pain control, which
was marginally less for the treatment for recurrent apthous
stomatitis (minor).