Formulation and Evaluation of Diclofenac Potassium Gel in Sports Injuries with and without Phonophoresis

Abstract

Background: Pain remains a global public heath priority. Phonophoresis, also known as sonophoresis or ultrasonophoresis, is when an ultrasound is used to maximize the effects of a topical drug. Purpose: The objective of this study was to test, in patients injured in sports or accidents (N = 200), the efficacy of diclofenac potassium (DK) 6%, 4%, and 2% formulated gels with and without phonophoresis in comparison with market available standard diclofenac sodium (DS or DN) gel. Methods: The patients were enrolled after informed consent. By using the lottery method, 100 patients were randomly segregated into five groups without phonophoresis and repeated similarly with phonophoresis at a frequency of 0.8 MHz, an intensity of about 1.5 W/cm², and at continuous mode (2:1). Group-1 was treated with 6% DK gel, group-2 was treated with 4% DK gel, group-3 was treated with 2% DK gel, group-4 was treated with 4% DS gel and group-5 was given control gel three to four times a week for 4 weeks. The patients were screened by using NPRS and WOMAC scales. They were assessed on the baseline, 4th session, 8th session, 12th session, and 16th session. Results: Significant dose-dependently relief was observed in NPRS (Numeric Pain Rating Scale) and the WOMAC (Western Ontario McMaster Osteo-Arthritis) index for pain in disability and stiffness for each group treated with DK gel compared to DS gel. Phonophoresis increased these benefits significantly when used after topical application of DK gel or DS gel, and the dose-dependent effects of DK gel plus phonophoresis were stronger than the dose-dependent effects of DS gel plus phonophoresis. The faster and profounder relief was due to phonophoresis, which allows more penetration of the DK gel into the skin as compared to the direct application of DK gel in acute, uncomplicated soft tissue injury, such as plantar fasciitis, bursitis stress injuries, and tendinitis. In addition, DK gel with phonophoresis was well tolerated. Thus, in this personalized clinical setting, according to the degree of inflammation or injured-induced pain, disability, and stiffness, DK gel 6% with phonophoresis appeared more effective and thus more recommendable than DS gel 6% alone or DS gel 6% combined to phonophoresis.

Keywords: diclofenac potassium gel; diclofenac sodium gel; pain; phonophoresis; sport injuries.

Figure 1

Mechanism of action of diclofenac potassium. NF-κb: Nuclear Factor-Kappa B; COX-2: Cyclooxygenase-2; PGE2: Prostaglandin E2 (dinoprostone); IL-1β: Interleukin-1beta (lymphocyte activating factor (LAF)); IL-6: Interleukin-6 (B-cell stimulatory factor -2 (BSF-2)); IL-8: Interleukin-8 (α chimiokine); TNF-α: Tumor Necrosis Factor-alpha; VEGF: Vascular Endothelial Growth Factor.

Figure 2

Incidence (%) of patients with sport-related injuries (N = 200) before treatment (which were then subsequently treated). * Means pain in muscles and soft tissues.

Figure 3

Swelling-related changes on the baseline, 4th session, 8th session, 12th session, and 16th session of Diclofenac potassium (DK) treatment (a) with phonophoresis (b) without phonophoresis, in sports-injured patients. Diclofenac sodium (DS) was used as a standard control. Control group is the placebo. Statistical significance (p-values) is detailed in the main text. ns = no significant; p < 0.05 *, p < 0.01 **, p < 0.001 ***.

Figure 4

NPRS-related changes on the baseline, 4th session, 8th session, 12th session, and 16th session of Diclofenac potassium (DK) treatment (a) with phonophoresis (b) without phonophoresis, in sports-injured patients. Diclofenac sodium (DS) was used as a standard control. Control group is the placebo. Statistical significance (p-values) is detailed in the main text. ns = no significant; p < 0.05 *, p < 0.01 **, p < 0.001 ***. NPRS: Numerical Pain Rating Scale.

Figure 5

Index of WOMAC ADLs on the baseline, 4th session, 8th session, 12th session, and 16th session of Diclofenac potassium (DK) treatment (a) with phonophoresis (b) without phonophoresis, in sports-injured patients. Diclofenac sodium (DS) was used as a standard control. Control group is the placebo. Statistical significance (p-values) is detailed in the main text. ns = no significant; p < 0.05 *, p < 0.01 **, p < 0.001 ***. WOMAC: Western Ontario and McMaster Universities Arthritis Index, ADLs: activities of daily living.

Figure 6

Index of WOMAC pain on the baseline, 4th session, 8th session, 12th session, and 16th session of Diclofenac potassium (DK) treatment (a) with phonophoresis (b) without phonophoresis, in sports-injured patients. Diclofenac sodium (DS) was used as a standard control. Control group is the placebo. Statistical significance (p-values) is detailed in the main text. ns = no significant; p < 0.05 *, p < 0.01 **, p < 0.001 ***. WOMAC: Western Ontario and McMaster Universities Arthritis Index.

Figure 7

Index of WOMAC stiffness on the baseline, 4th session, 8th session, 12th session, and 16th session of Diclofenac potassium (DK) treatment (a) with phonophoresis (b) without phonophoresis, in sports-injured patients. Diclofenac sodium (DS) was used as a standard control. Control group is the placebo. Statistical significance (p-values) is detailed in the main text. ns = no significant; p < 0.05 *, p < 0.01 **, p < 0.001 ***. WOMAC: Western Ontario and McMaster Universities Arthritis Index.

Figure 8

Consolidated Standards of Reporting Trials (CONSORT). DK stands for Diclofenac potassium, and DS means Diclofenac sodium (used as a standard). Control group is the placebo.

Figure 9

(A) Phonophoresis (ultrasound) for the treatment of sport injuries, (B) Phonophoresis on a patient with neck pain after applying 4 pumps of DK gel, (C) Applying 4 pumps of DK gel on a patient foot, (D) Phonophoresis on a patient foot.

Figure 10

Numerical Pain Rating Scale (NPRS) indicating different intensities of pain: 0 means no pain, 5 reveals moderate pain, and 10 indicates severe pains.

Figure 11

Western Ontario McMaster Osteo-Arthritis (WOMAC) scale/index indicating three parameters: pain, stiffness, and functional activities.