Design, Characterization and Evaluation of Topical Analgesic gel for Acute and Chronic pain

Madhav B. Korde*¹, Suparna S. Bakhle², Vaibhav P. Uplanchiwar¹, Vinod M. Thakare¹,

Anshu R. Dudhe¹

¹Nagpur College of Pharmacy, Wanadongri, Hingna Road, Nagpur - 441110 (M.S.)

²Priyadarshini J.L. College of Pharmacy, Electronic Zone Building, MIDC,

Hingna Road, Nagpur - 440016 (M.S.)

*Corresponding Author E-mail: madhavkorde07@gmail.com

ABSTRACT:

Topical gel preparations are designed for application on the skin or mucosal surfaces to deliver medications effectively, bypassing first-pass metabolism and enhancing localized therapeutic effects, particularly in pain management and the treatment of skin conditions. Nonsteroidal anti-inflammatory drugs (NSAIDs), known for their potent anti-inflammatory and analgesic properties, are increasingly favored for topical administration to mitigate the adverse effects often associated with their oral counterparts. In this context, hydrophilic polymers such as Carbopol 940 have been employed to develop topical hydrogel formulations containing diclofenac sodium. The objective of the study was to formulate and assess various topical dosage forms containing diclofenac sodium, methyl nicotinate, and methyl salicylate, and to evaluate their therapeutic efficacy in managing both acute and chronic pain. Six batches of a gel formulation combining methyl nicotinate, diclofenac sodium, and methyl salicylate were developed and tested.

KEYWORDS: Methyl nicotinate, Diclofenac Sodium, Franz Diffusion cell, Analgesic, Anti-inflammatory.

INTRODUCTION:

Topical drug delivery system: Topical drug delivery systems provide a non-invasive approach to administering active pharmaceutical ingredients directly to the skin or mucosal surfaces, ensuring localized therapeutic effects while bypassing the first-pass metabolism. These systems are particularly advantageous in managing pain and treating skin conditions, offering benefits such as enhanced patient compliance, precise drug targeting, and a reduction in systemic side effects^1,2.

Nonsteroidal anti-inflammatory drugs (NSAIDs), recognized for their powerful analgesic and anti-inflammatory properties, are increasingly being formulated into topical gels to mitigate the adverse effects associated with oral administration.

In this study, the hydrophilic polymer Carbopol 940 was utilized to craft an innovative topical hydrogel formulation incorporating diclofenac sodium, methyl nicotinate, and methyl salicylate. The objective was to assess the therapeutic efficacy of these formulations in addressing both acute and chronic pain, with six batches of the gel meticulously prepared and evaluated for their potential in clinical applications^3,4,5.

Topical gel preparations deliver drugs directly to the skin or mucosal surfaces, avoiding oral administration-related adverse reactions, and are increasingly preferred over oral forms.These topical analgesics are employed to manage a range of painful conditions, from acute and chronic pain to neuropathic pain. The selection of topical therapy is tailored to the specific condition, with options including NSAIDs, rubefacients, low-dose capsaicin, and local anesthetics, particularly for neuropathic pain management^6,7.

Some marketed preparations of topical gel having analgesic and anti-inflammatory activity are as follows:

Ark Gel, Delete Gel, Desolve Gel, Dolentia Gel, Dolosig Gel, DSignoflam Gel, Duoflam Gel, Flexabenz Gel.

Table 1: Formulation Table of Topical Gel

Ingredients	Formulation
	F-1	F- 2	F- 3	F- 4	F- 5	F- 6
Diclofenac sodium (g)	0.5	0.5	0.5	0.5	0.5	0.5
Methyl nicotinate (g)	0.15	0.2	0.25	0.15	0.2	0.25
Methyl salicylate (ml)	5	5	5	5	5	5
Menthol (g)	2.5	2.5	2.5	2.5	2.5	2.5
Linseed oil (ml)	1.5	1.5	1.5	-	-	-
Turpentine oil (ml)	-	-	-	1.5	1.5	1.5
Benzyl alcohol (ml)	1.5	1.5	1.5	1.5	1.5	1.5
Carbopol base (1%) (g)	0.5	0.5	0.5	0.5	0.5	0.5
Distilled water q.s. (g)	50	50	50	50	50	50

MATERIALS AND METHODS:

Method of preparation of Carbopol 940 base (1%):

1) Carbopol-940 colloidal dispersions were prepared using distilled water at 1% concentration.

2) Stored for 24hours for complete swelling.

3) After complete dispersion, the solutions were left to swell for 24hours.

4) After 24hrs, the mixture was stirred at a mechanical stirrer at 500rpm to remove the air bubbles in it.

5) Then Triethanolamine to it with continuous stirring to adjust the required pH of carbopol base to formulate gel i.e., 6.7-6.9. 

Gel Preparation Method: (Table-1)

1. Weigh the necessary quantity of 1% Carbopol-940 base into a beaker, then add benzyl alcohol while stirring continuously.

2. Dissolve the required quantity of Diclofenac sodium in Iso-propyl alcohol and add this to the above phase with continuous stirring.

3. Add to this methyl nicotinate by dissolving it by heating it in distilled water and adding to the above phase with continuous stirring.

4. Dissolve the crushed menthol powder in warmed isopropyl alcohol to form a clear liquid, then add it to the aqueous phase with continuous stirring.

5. In a separate beaker, dissolve methyl salicylate in the oil phase containing linseed oil or turpentine oil, then add this mixture to the aqueous phase with continuous stirring.

Add distilled water gradually to bring the mixture to the desired volume, ensuring continuous stirring throughout the process.

RESULTS:

Preformulation studies of Diclofenac sodium (B.P.), Methyl nicotinate, Methyl salicylate

Identification of drug properties:

The Organoleptic properties, Melting point and solubility determination of the drug and excipient has been given in Table-2.

The melting point and solubility measurements were done to identify Diclofenac sodium, methyl nicotinate, and methyl salicylate, which are used to identify drugs^8,9,10,11.

Table 2: Organoleptic Properties, Melting point and solubility determination.

Sr. No.	Drug	Organoleptic properties	Observation
1	Diclofenac sodium	Colour	White to off-white powder
		Odour	Odourless
		Melting Point	284°C
		Solubility	Soluble in isopropyl alcohol and methanol
2	Methyl nicotinate	Color	White to yellowish crystals
		Taste	Irritating/ characteristics
		Odour	Irritating
		Melting Point	41°C
		Solubility	Soluble in water
3	Methyl salicylate	Colour	Colourless or slightly yellowish liquid
		Odour	Irritating
		Boiling Point	222°C
		Solubility	Soluble in organic solvents like methanol, ethanol

Micromeritic Properties:

Study evaluated flow properties of Diclofenac sodium and Methyl nicotinate by assessing key parameters such as true density, tapped density, Carr's index, and Hausner's ratio, angle of repose ^13,14,15. (Table-3).

Table 3: Micromeritic Characteristics of Diclofenac Sodium and Methyl Nicotinate

Sr. No	Micromeritic property	Results
		Diclofenac Sodium	Methyl nicotinate
1	Bulk density	0.86 g/ ml	0.54 g/ ml
2	Tapped density	1.12 g/ ml	0.57 g/ ml
3	Angle of repose	21.38˚	19.23˚
4	Carr’s Index	13.43	12.02
5	Hausner’s ratio	1.18	1.05

Drug-excipients compatibility studies: 

Fourier Transformer-Infra red (FT-IR) studies

Fig 1: IR- pure diclofenac sodium

Fig 2: IR- Methyl salicylate

Fig 3: IR- Carbopol 940

Fig 4: IR - Physical Mixture

The IR spectrum of pure diclofenac sodium exhibits distinct absorption bands at 1568.50, 1505.05, 3378.26, 1170.07, and 748.16 cm⁻¹, corresponding to C= C, N-H, C- N, and C- Cl stretching vibrations.

For methyl nicotinate, the IR spectrum displays characteristic peaks at 1721.81 cm⁻¹, 1582.12 cm⁻¹, 1285.80 cm⁻¹, and 1112.98 cm⁻¹, which are indicative of COOR, C=C, O, and N stretching, respectively.

The IR spectrum of pure methyl salicylate shows prominent absorption peaks at 3186.63 cm⁻¹, 1673.41 cm⁻¹, 1481.87 cm⁻¹, and 1203.51 cm⁻¹.

Carbopol 940's IR spectrum (Figure 7.4) reveals characteristic absorption at 1709.19 cm⁻¹ (C= O stretching) and 1247.93 cm⁻¹ (C-O stretching).

FTIR spectrum of all systems combined showed key absorption peaks in the physical mixture at 3378.26 cm⁻¹, 3171.46 cm⁻¹, 1568.50 cm⁻¹, 1505.05 cm⁻¹, 1170.07 cm⁻¹, 748.16 cm⁻¹, and additional peaks at 846.82 cm⁻¹, 803.59 cm⁻¹, and 752.21 cm⁻¹.

The spectra analysis revealed no new peaks in the physical mixture, indicating no physical or chemical interactions between drugs and other excipients.

Differential Scanning Calorimetry:

Fig.5: DSC thermogram- Diclofenac sodium

In DSC analysis, the thermogram of diclofenac sodium exhibited an endothermic peak at 284.40°C, corresponding to its melting point. Onset temperature was recorded at 281.43°C, with an observed heat of fusion of -189.15 J/g.

Fig.6: DSC thermogram of Methyl Nicotinate.

DSC thermogram of methyl nicotinate shows an endothermic peak at 42.20 °C, indicating its melting point. The onset temperature was measured at 137.58°C, with a recorded heat of fusion of -833.02 J/g.

Fig.7: DSC thermogram of mixture.

DSC conducted a compatibility study on the drug and excipients, revealing no major changes in the thermogram, confirming the excipient's compatibility with the drug.

SPECTROMETRIC ANALYSIS:

Determination of λ max and a calibration curve of Diclofenac sodium at 276nm: Maximum absorbance of diclofenac sodium was found at 276 nm, consistent with the reference wavelength. It follows Beer-Lambert's law within the 10-30 µg/ml concentration range, displaying a linear relationship.

Fig 8: λ max Spectrum of Diclofenac sodium in Phosphate Buffer-pH 6.8 and Standard calibration curve.

Determination of λ max and calibration curve- Methyl nicotinate 219nm: maximum absorbance of methyl nicotinate was observed at 219 nm, which adhered to Beer-Lambert's law within concentration range of 2- 10 µg/ ml, exhibiting a linear relationship in a pH 6.8 environment.

Fig.9: λ max Spectrum of Methyl nicotinate in Phosphate Buffer-pH 6.8 & Standard Calibration Curve

Determination of λ max and calibration curve- Methyl salicylate at 237.50nm:

Methyl salicylate exhibited maximum absorbance at 237.50nm, adhering to Beer-Lambert's law within concentration range of 2- 10µg/ml, with a linear relationship observed in a pH 6.8 environment.

Fig 10: λ max Spectrum of Methyl salicylate and Standard Calibration Curve

Topical Gel Evaluation:

1. Physical Appearance of Gel:

Evaluation of the gel's physical appearance was conducted through visual inspection. The gels were examined for clarity and the absence of any aggregates. The commercially available Diclowin gel was used as the standard for comparison^19.20.

Fig 11: Formulated Gel preparation

2. Colour, homogeneity, pH, spreadability and viscosity^21,22,23,24.

Gel formulations were prepared and tested, with all formulations exhibiting good consistency, with the most homogeneous being F1 to F4.

The prepared formulations' viscosity was measured using a Brookfield digital viscometer, revealing a range of 27333.33±52.75 to 30342.67±40.93 cps, making them suitable for topical application.

3. Drug Content: Drug content in Diclofenac sodium and Methyl nicotinate gel was determined using standard calibration curves, with F3 formulation having the highest amount loaded, optimizing for future studies.

4. In-vitro release study: 

After 2 hours, drug release from formulations F-1 to F-6 ranged between 81.53% and 95.54% for Diclofenac sodium and between 75.48% and 84.83% for Methyl nicotinate. The commercially available Diclowin gel was used as a standard for comparison.

Fig. 12: Comparison of % Drug release profile of formulated gel with marketed gel

Table 4: Colour, Homogeneity and Spreadability of Gel and Viscosity of Gel

Formulation	Colour	Homogeneity	pH mean ± S.D.	Spreadability ± S.D.	Viscosity
					RPM	(cps) ± S.D.
F-1	White	Excellent	6.39 ± 0.01	7.36 ±0.37	10	29028.33 ± 61.13
F-2	White	Good	6.91 ± 0.02	6.16 ± 0.65	10	28800 ± 100
F-3	White	Excellent	6.35 ± 0.01	6.56 ± 0.2	10	27333.33 ± 52.75
F-4	White	Good	6.63 ± 0.25	7.06 ± 0.21	10	28516.67 ± 60.72
F-5	White	Excellent	6.48 ± 0.13	7.1 ± 0.2	10	30342.67 ± 40.93
F-6	White	Excellent	6.37 ± 0.06	6.8 ± 0,7	10	29243.33 ± 51.31
M (Marketed)	White	Excellent	6.64 ±0.14	7.0 ±0.17	10	27090 ± 79.37

mean±S.D. n = 3 

Table 5: Determination of Drug Content

Formulation	% Drug Content
	Diclofenac Sodium	Methyl Nicotinate
F-1	92.2 ± 0.10%	89.31± 0.72 %
F-2	91.53 ± 0.30 %	92.16 ± 0.20 %
F-3	98.16 ± 0.28 %	96.63 ± 0.12 %
F-4	84.88 ± 0.59 %	85.47 ± 0.27 %
F-5	90.93 ± 0.80 %	91.20 ± 0.43 %
F-6	91.60 ± 0.20 %	96.03 ± 0.28 %
M (Marketed)	96.40 ± 0.42 %	NA

Each data was representing mean  ±  S.D.  (n=3)

Table 6: % Durg Release profile of Diclofenac sodium

Time (min)	% Drug Release
	F- 1	F -2	F- 3	F- 4	F -5	F- 6	M
0	00	00	00	00	00	00	00
15	12 ± 0.28	9.7 ± 0.06	10.7 ± 0.12	11.67± 0.08	7.16 ±0.10	18.12 ± 0.06	17.8 ± 0.08
30	17.48 ±0.1	19 ± 0.13	21.03±0.18	20.38±0.12	20.06±0.1010	23.61±0.08	29.74±0.11
45	30.06±0.08	27 ± 0.10	28.77±0.11	32 ± 0.08	26.83±0.13	34.58±0.10	34.58±0.08
60	39.41±0.12	35.22±0.07	52 ± 0.15	42.32 ± 0.10	36.19 ± 0.08	53.61 ± 0.06	50.06 ±0.04
75	51.35±0.18	46.19±0.12	62 ± 0.20	49.09±0.12	50.38±0.15	64.9±0.12	66.19±0.10
90	62 ± 0.10	65.78±0.06	71.03± 0.12	67.48±0.11	62.05±0.08	77.41± 0.3	80.7±0.20
105	78.45±0.09	72.32±0.20	84.9±0.15	81.35±0.10	73.61±0.18	85.54±0.10	84.9±0.16
120	91.67±0.12	81.53±0.13	93.2±0.09	84.25±0.11	86.19±0.06	95.54±0.20	96.51±0.10

Mean±S.D. (n= 3) M- marketed

Table 7: % Drug release profile of Methyl nicotinate

Time (min)	% Drug Release
	F1	F2	F3	F4	F5	F6
0	0	0	0	0	0	0
15	14.35±0.02	15±0.04	13.54±0.02	13.54±0.04	18.22±0.03	17.41 ±0.05
30	28.7 ±0.05	26.12±0.03	27.09 ±0.04	27.74 ±0.03	24.67 ±0.05	29.19 ±0.04
45	40.8 ±0.07	31.77 ±0.03	38.38 ± 0.04	40.8 ±0.04	36.12 ±0.05	36.12 ±0.02
60	52.32 ±0.05	40 ± 0.05	45.96 ± 0.03	46.29 ±0.05	44.35 ±0.07	43.38 ±0.03
75	61.93 ±0.08	51.77 ±0.03	55.96 ± 0.05	55.16 ±0.03	55.16 ±0.04	57.74 ±0.06
90	69.93 ±0.04	54.51 ±0.07	63.06 ±0.02	68.7 ±0.06	68.7±0.04	68.87 ±0.03
105	76.12 ±0.02	65.96 ±0.04	71.45 ±0.02	78.54 ±0.05	78.52 ±0.04	76.93 ±0.03
120	83.54 ±0.04	75.48 ±0.05	84.83 ± 0.03	84.83±0.04	82.09±0.05	83.7 ±0.03

mean ± S.D. (n=3)

Fig. 13: Comparison of % Drug release profile of formulated gel with marketed gel

CONCLUSION:

This study successfully formulated and evaluated topical gels containing diclofenac sodium, methyl nicotinate, and methyl salicylate using Carbopol 940 as the base. Topical NSAIDs offer localized pain relief with fewer systemic side effects compared to oral forms. In this study, the F3 gel formulation, containing diclofenac sodium, methyl salicylate, and methyl nicotinate, demonstrated superior drug diffusion and anti-inflammatory effects. The F3 formulation showed maximum drug release, with 93.20% for diclofenac sodium and 84.83% for methyl nicotinate. This combination could improve pain management and quality of life, particularly in acute and chronic pain conditions.

DISCUSSION:

This study developed and evaluated six topical gels (F1-F6) containing diclofenac sodium, methyl nicotinate, and methyl salicylate for pain relief. The F3 gel formulation stood out due to its smooth texture, ideal pH, excellent spreadability, high drug content (98.16% diclofenac sodium, 96.63% methyl nicotinate), and superior in-vitro drug release. Safety tests confirmed no skin irritation, and F3 showed effective analgesic and anti-inflammatory properties, making it a strong candidate for further research.

FUTURE SCOPE:

1.   Further studies can optimize the content of the three active ingredients using advanced analytical methods.

2.   Validation of the proposed formulation method is necessary.

3.   Future research could explore more effective combinations of these active ingredients for enhanced therapeutic outcomes.

REFERENCES:

1. Monica AS, Gautami J. Design and evaluation of topical hydrogel formulation of diclofenac sodium for improved therapy. International Journal of Pharmaceutical Sciences and Research. 2014; 1; (5): 1973.

2. Pravin S, Nanthagopal P, Ayyappan T. Development and Evaluation of Polyherbal Formulation for the Treatment of Dengue Fever. Research Journal of Pharmacy and Technology. 2022; 15(11): 4981-4986.

3. Shinde PP, Khule SD, Sonawane S, Shelke S. Analgesic activity and anti-inflammatory activity of methanolic extract of plant Sida cordata in carrageenan-induced paw edema in rats. Asian Journal of Pharmaceutical Research. 2021; 11(3): 143-146.

4. Munshi PP, Mohale DS, Akkalwar R, Chandewar AV. Formulation and Evaluation of Diclofenac gel. Research Journal of Pharmacy and Technology. 2011; 4(9): 1394-1399.

5. Sharadha M, Gowda DV, Vishal Gupta N, Akhila AR. An overview on topical drug delivery system–updated review. Int. J. Res. Pharm. Sci. 2020; 9; (1): 368-385.

6. Rawat S, Gupta A. Spectrophotometric method for simultaneous estimation of nimesulide and diclofenac sodium in pharmaceutical dosage forms. Asian Journal of Pharmaceutical Analysis. 2011; 1(4): 85-87.

7. Indian Pharmacopeia (IP) 2018, vol. II, page no.1808

8. Hadgraft J, Lane ME. Skin permeation: the years of enlightenment. International Journal of Pharmaceutics. 2005; 305(1-2): 2-12.

9. Ansel HC, Allen LV. Pharmaceutical Dosage Forms and Drug Delivery System. 7th ed. Baltimore: Lippincott Willams and Wilkens, 2000, 244-265.

10. Mishra AN. Controlled and Novel Drug Delivery. New Delhi: CBS Publishers and Distributors; 1997. 107-109.

11. Hasan S, Bhandari S, Sharma A, Garg P. Emulgel: A review. Asian Journal of Pharmaceutical Research. 2021;11(4): 263-268.

12. Monica AS, Gautami J. Design and evaluation of topical hydrogel formulation of diclofenac sodium for improved therapy. International Journal of Pharmaceutical Sciences and Research. 2014; 1; (5):1973.

13. Shraddha M, Anuradha S. Formulation and evaluation of Emulgel containing Coriandrum sativum seeds oil for Anti-inflammatory activity. Journal of Drug Delivery and Therapeutics. 2019; 2(9): 124-130.

14. A. salomy Monica, J. gautami. Design and Evaluation of Topical Hydrogel Formulation of Diclofenac Sodium for Improved Therapy. International Journal of Pharmaceutical Sciences and Research. 5(5): 1973-1980.

15. Aulton pharmaceutics, The design and Manufacturing of Medicines. Fourth edition - 190-197.

16. Sagar Suman Panda, M.E.Bhanoji Rao. Spectrophotometric Estimation of Xanthinol Nicotinate In Bulk and Sustained Release Tablet Dosage Forms. International Journal of Current Pharmaceutical Research 2010; 2(1)

17. McCarberg B, D'Arcy Y. Options in topical therapies in the management of patients with acute pain. Postgraduate Medicine. 2013; Jul 2;125(sup1):19-24.

18. Landa, P., & Vanková, K. Plant-derived products in pain management. Journal of Ethnopharmacology. 2016; 189:43-63.

19. Baboota, S., Alam, M. S., & Ali, J. Formulation and evaluation of a topical nanoemulsion gel for chronic arthritis in a rabbit model. AAPS PharmSciTech, 2013; 14(4): 1237-1245.

20. Patel D, Naik S. A review on drug delivery systems for pain management. Int J Pharm Sci Res. 2014; 5(6): 2243-2254.

21. Ying L, Li Y. Formulation and evaluation of a new topical gel containing an anti-inflammatory drug. J Drug Deliv Sci Technol. 2017; 38: 79–87.

22. Barry BW. Novel mechanisms and devices to enable successful transdermal drug delivery. Eur J Pharm Sci. 2001;14(2): 101–114.

23. Anselmo AC, Mitragotri S. An overview of clinical and commercial impact of drug delivery systems. J Control Release. 2014; 190: 15–28.

24. Keating GM. Diclofenac gel 1%: a review of its use in the treatment of actinic keratosis. Drugs Aging. 2013; 30(10): 779–788.

Received on 19.08.2024      Revised on 22.03.2025

Accepted on 01.10.2025   Published on 13.01.2026

Available online from January 17, 2026

Research J. Pharmacy and Technology. 2026;19(1):432-438.

DOI: 10.52711/0974-360X.2026.00063

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