Formulation and Evaluation of an Emulgel Containing Piroxicam and Lidocaine for the Treatment of Musculoskeletal Disorders

Musculoskeletal disorders (MSDs), including arthritis, sprains, and muscle strains, are common conditions affecting muscles, joints, bones, tendons, and ligaments, and are a leading cause of pain and disability worldwide, often resulting in long-term functional limitations and reduced quality of life. According to the World Health Organization, MSDs affect over 1.71 billion individuals globally, ranking among the top causes of years lived with disability. ¹ Conventional management typically involves systemic administration of NSAIDs and analgesics. While effective, prolonged use can cause gastrointestinal irritation, hepatotoxicity, and nephrotoxicity². Topical drug delivery systems have emerged as safer, targeted alternatives, delivering the active drug directly to the site of inflammation, minimizing systemic absorption, and reducing adverse effects³. They also improve patient compliance and bypass first-pass metabolism, which is important in chronic MSDs?. Among topical systems, emulgels offer enhanced drug permeation, controlled release, improved stability, and non-greasy application, making them particularly suitable for hydrophobic drugs.??? Incorporating oil-in-water or water-in-oil emulsions into a gel matrix allows dual drug release mechanisms, supporting sustained and effective therapy. Piroxicam, an oxicam-class NSAID, inhibits cyclooxygenase enzymes, reducing prostaglandin synthesis and inflammation?, but oral use may cause gastrointestinal complications. Lidocaine, an amide-type local anesthetic, blocks voltage-gated sodium channels, providing rapid localized analgesia?. To the best of our knowledge, this is the first study to formulate and evaluate a Piroxicam-Lidocaine emulgel, offering a novel synergistic dual-action therapy that targets both inflammation and pain. Therefore, this study aimed to develop and evaluate a Piroxicam-Lidocaine emulgel for topical administration, with the goal of achieving localized, sustained therapeutic action, enhanced patient compliance, and minimized systemic toxicity in the management of MSDs.

MATERIALS AND METHODS

MATERIALS

The active pharmaceutical ingredients (APIs), Piroxicam and Lidocaine, were procured from Balaji Drugs. The excipients-Liquid Paraffin, Tween 80, Span 80, Propylene Glycol, Methyl Paraben, and Propyl Paraben were supplied by Modern Industries, Nashik. Carbopol 940, used as the gelling agent, was obtained from Loba Chemie Pvt. Ltd., while Ethanol was sourced from Ozone, India. Triethanolamine, used for pH adjustment and to facilitate gel formation, was provided by Chemsworth.

METHOD

Preparation of Emulgel

The emulgel was prepared using three steps. ?

Formulation of Emulsion

An oil-in-water (O/W) emulsion was prepared by separately heating the oil and aqueous phases. The oil phase consisted of Span 80 (lipophilic emulsifier) and Liquid Paraffin, which were thoroughly mixed. The aqueous phase contained Tween 80 (hydrophilic emulsifier), Propylene Glycol (humectant), and preservatives (Methyl Paraben and Propyl Paraben), along with Piroxicam and Lidocaine dissolved in Ethanol. The oil phase was gradually added to the aqueous phase with continuous stirring to form a uniform emulsion, which was then allowed to cool to ambient temperature

Formulation of Gel base

Carbopol 940 was dispersed in distilled water and allowed to hydrate for several hours. The hydrated dispersion was stirred slowly using a mechanical stirrer until a consistent gel was obtained. The pH of the gel was adjusted to 6.0–6.5 using triethanolamine to ensure optimal consistency and skin compatibility.

Incorporation of Emulsion into Gel Base

The prepared emulsion was gradually mixed with the gel base in a 1:1 ratio under continuous gentle stirring to ensure uniformity. The resulting emulgel was transferred to suitable containers and stored for further evaluation.

Formulation of emulgel

The composition of different formulations of Piroxicam and Lidocaine emulgel is shown in Table 1?.

Table 1: Composition Of Different Piroxicam-Lidocaine Emulgel Formulations

(i) Physical Examination

The formulated emulgel was visually examined for colour, homogeneity, texture, phase separation, and grittiness. The evaluation ensured a uniform appearance with even distribution of ingredients. Formulations showing consistent colour, smooth texture, no visible phase separation, and absence of lumps or undissolved particles were considered acceptable¹?.

(ii) pH

The pH of the emulgel was measured using a calibrated digital pH meter. One gram of the emulgel was dispersed in 100 mL of distilled water and allowed to stand for 2 h to ensure complete interaction. Measurements were performed in triplicate, and the average pH value was recorded¹¹.

(iii) Drug Content

For drug content estimation, 1 g of emulgel was weighed and dissolved in 100 mL of phosphate buffer (pH 7.4) with continuous stirring. The solution was filtered through Whatman filter paper and diluted appropriately. Absorbance was recorded at specific wavelengths for Piroxicam and Lidocaine using a UV-visible spectrophotometer. Drug concentrations were calculated using their respective standard calibration curves, and the percentage of drug content was determined¹².

(iv) Viscosity

The viscosity of the emulgel was determined using a Brookfield viscometer (spindle No. 64) at 10 rpm. A measured quantity of the formulation was placed in a beaker, and readings were performed at room temperature. Measurements were carried out in triplicate, and values were expressed in mPa·s¹³.

(v) Spreadability

Spreadability was assessed using the glass slide method. A fixed quantity of emulgel was placed between two glass slides, and a 500 g weight was applied to the upper slide for 1 min. The time required for the upper slide to move a specified distance due to the applied weight was recorded, and Spreadability was calculated¹² ¹³.

(vi) Extrudability

Extrudability was evaluated to determine how easily the emulgel could be dispensed from a tube. Approximately 10 g of the formulation was filled into a collapsible tube and compressed using a 500 g weight. The amount of emulgel released within 30 s was collected and weighed. The test was repeated three times, and the average value was recorded. Higher extrudability values indicate better ease of application and patient usability¹?.

(vii) Stability

Stability tests for the gels were performed according to ICH guidelines. The gel samples were stored in stability chambers for 3 months under the following conditions: 25 ± 2 °C, 60 ± 5% RH (room temperature) and 40 ± 2 °C, 75 ± 5% RH (accelerated conditions). Samples were withdrawn at 0, 1, 2, and 3 months for stability analysis. After 3 months, assays were conducted to determine any potential interactions between the drugs and other formulation ingredients, as well as to assess changes in physical appearance, pH, viscosity, drug content, and in vitro drug release¹?.

(viii) In Vitro Drug Permeation Studies

In vitro drug release was performed using a Franz diffusion cell with a cellophane membrane as the barrier. The receptor chamber was filled with phosphate buffer (pH 7.4) and maintained at 37 ± 0.5 °C with continuous stirring. A measured amount of emulgel was applied to the donor compartment. Samples (1 mL) were withdrawn at predetermined intervals and immediately replaced with fresh buffer. Drug content was analyzed using a UV-visible spectrophotometer, and cumulative release of Piroxicam and Lidocaine was calculated¹?.

Ethical Statement

This study did not involve the use of human participants or experimental animals. Therefore, approval from an institutional Ethics Committee was not required.

RESULTS AND DISCUSSION

1. Preformulation Studies

Table 2: Preformulation Study

2. Melting Point determination

The melting point of piroxicam was found to be 200 °C (practically), as reported in the literature, thus indicating the purity of the sample.

The melting Point of Lidocaine was found to be 70 °C (practically), as reported in the literature, thus indicating the purity of the sample.

3. UV-Visible Spectroscopic scanning-spectral analysis

Calibration Curve of Piroxicam

A calibration curve for Piroxicam was developed by plotting concentration against absorbance. The absorbance readings are shown in Table 1, and the corresponding graph is illustrated in Figure 1. The curve demonstrated excellent linearity over the concentration range of 5–25 µg/mL at 353 nm, with a correlation coefficient (R²) of 0.9996. This standard curve was subsequently used for determination of drug content and in vitro drug permeation analysis.

Table 3: Calibration Curve Data for Piroxicam

Calibration Curve of Lidocaine

A standard calibration curve for Lidocaine was constructed by plotting absorbance against concentration. The absorbance readings are listed in Table 2, and the corresponding calibration graph is shown in Figure 2. The curve exhibited good linearity across the concentration range of 5–25 µg/mL at 263 nm, with a correlation coefficient (R²) of 0.9992. This curve was used for quantification of Lidocaine in both drug content estimation and in vitro drug permeation studies.

Table 4: Calibration Curve Data for Lidocaine

The UV-Visible spectral analysis confirmed λ_max of Piroxicam at 353 nm and Lidocaine at 263 nm. Both drugs showed excellent linearity, indicating the method is precise, accurate, and suitable for drug estimation and in vitro release studies.

2. FTIR

The FTIR spectra of pure Piroxicam and Lidocaine, as well as their respective emulgel formulations, were analyzed (Figures 3 & 4; Tables 5 & 6). All characteristic functional group peaks of the drugs were clearly observed, and no significant shifts, disappearance, or broadening of peaks occurred in the formulations. This indicates that there were no notable interactions between the drugs and excipients, confirming their compatibility and suitability for emulgel development.

2. Evaluation of Emulgel
   1. Physical Examination

All six formulations (F1–F6) were assessed for physical characteristics including colour, texture, homogeneity, phase separation, and grittiness. All formulations exhibited a whitish appearance, uniform consistency, and smooth texture. No phase separation or grittiness was observed, indicating physically stable and well-prepared emulgels.

The pH values of formulations F1–F6 ranged from 6.5 to 7.2, within the ideal range for topical preparations, ensuring safety and non-irritancy.

3. Drug Content

The Piroxicam content ranged from 92–97%, reflecting efficient drug incorporation. Lidocaine levels ranged from 90–96%, indicating uniform dispersion in the emulgel.

Table 9: Percentage Of Piroxicam in Formulations

Table 10: Percentage Of Lidocaine in Formulations

1. 4. Viscosity

All formulations exhibited viscosity values between 6759–8536 cps, confirming appropriate thickness for topical application and adequate Spreadability.

Table 11: Viscosity Of Formulations

1. 4. Spreadability

Formulations F1–F6 showed spreadability values of 5.7–8.5 cm, suitable for smooth topical application.

1. 4. Extrudability

All formulations showed satisfactory extrudability (1.05–3.80 g per three presses), ensuring easy dispensing.

Stability

The emulgel formulations were evaluated for stability over 3 months at room temperature (25 ± 1 °C) and elevated temperature (40 ± 1 °C). A slight gradual reduction in drug content was observed over the storage period, indicating that the formulations maintained good physical and chemical stability.

Table 14: Stability Of Formulations

Observation: There were no visible changes in color, texture, or phase separation during the 3- month period, indicating the emulgel formulations remained physically stable.

1. 4. In Vitro Drug Release Studies

The in vitro release study demonstrated that the emulgel formulations provided sustained release of Piroxicam and rapid release of Lidocaine, supporting the intended dual drug delivery system. Piroxicam release was studied over 6 hours to achieve prolonged anti-inflammatory effect, whereas Lidocaine release was monitored over 4 hours for immediate analgesic action.

Figure 6: In-vitro percentage drug release of Piroxicam

Figure 7: In-vitro percentage drug release of Lidocaine