Formulation and Evaluation of a Sustainable Analgesic Cream Utilizing Renewable Bio-Based Ingredients and Green Chemistry Design Principles

As pharmaceutical and consumer healthcare products continue to evolve through technological innovation, the reliance on synthetic active pharmaceutical ingredients (APIs) and petroleum-derived excipients has steadily increased. This trend is driven by factors such as manufacturing convenience, cost effectiveness, formulation robustness, and the need to meet evolving consumer expectations. Consequently, many topical formulations are composed predominantly of synthetic and petroleum-based ingredients.

While synthetic APIs remain essential for ensuring efficacy, quality, and regulatory compliance, growing interest has emerged in the use of naturally derived ingredients due to their renewable nature, biodegradability, and potential environmental benefits. Although numerous botanical actives such as Arnica montana,¹ turmeric extract² (Curcuma longa), and Calendula officinalis³ have been associated with wound-healing and anti-inflammatory properties, their broader adoption has been limited by formulation challenges, variability in composition, and insufficient clinical evidence.

A sustainable topical cream containing lidocaine HCl, zinc oxide, and benzalkonium chloride was developed for wound-healing and analgesic applications. Lidocaine HCl was incorporated as the primary local anesthetic to provide topical pain relief, while zinc oxide and benzalkonium chloride were included to support skin protection and wound healing through their soothing, barrier-forming, and antimicrobial properties.

Because excipients constitute the majority of topical formulations, formulation development focused on maximizing the use of renewable, naturally derived excipients while reducing dependence on conventional petroleum-derived materials. A green chemistry approach was applied throughout the formulation design process without compromising product functionality, stability, or sensory performance.

Starch⁴ was selected as a bio-based rheology modifier and texture-enhancing agent, sorbitol⁵ served as a naturally derived humectant and moisture-retention agent, coconut oil⁶ functioned as a renewable emollient and penetration-enhancing component, and beeswax⁷ was incorporated as a natural structuring and occlusive barrier-forming agent. These excipients were chosen based on their functional performance and favorable sustainability profiles. The formulation was designed to provide effective analgesic and wound-healing support while maintaining desirable physicochemical properties, including viscosity, spreadability, stability, skin feel, and overall user acceptability.

To validate this approach, the optimized bio-based cream was benchmarked against a leading commercial topical analgesic product formulated with synthetic excipients. Comparative evaluation focused on key quality and performance attributes, including formulation stability, sensory characteristics, viscosity, spreadability, drug release, and overall functionality. The findings demonstrate the potential of renewable, biodegradable excipients to serve as viable alternatives in topical pharmaceutical formulations, supporting both product performance and sustainability objectives.

Objective

To develop and evaluate a sustainable topical analgesic and wound-healing cream utilizing renewable bio-based excipients and green chemistry design principles, and to demonstrate that naturally derived excipients can achieve comparable or superior performance to conventional synthetic alternatives while maintaining product quality, stability, efficacy, and consumer acceptance.

Methods

Initial formulation development evaluated natural bioactive ingredients, including turmeric, calendula, and arnica extracts, in combination with sustainable excipients.

The various formulation versions and ingredient modifications are summarized below. All batches were manufactured in accordance with established standard operating procedures (SOPs). Formulations containing coconut oil and beeswax were heated to approximately 50 °C to ensure complete melting, homogeneous mixing, and uniform incorporation of all ingredients into the cream matrix.

Five formulation iterations were developed using varying combinations of active ingredients and excipients. Each formulation underwent preliminary evaluation based on visual appearance and viscosity, which were utilized as critical selection criteria for identifying the optimized formulation for further development and characterization.

Visual testing: All prototype formulations were evaluated for visual and sensory attributes to assess their suitability for topical application. Customer acceptance was determined based on key attributes, including appearance, texture, spreadability, skin feel, and overall sensory perception.

Viscosity testing: The rheological properties of all cream formulations were characterized using a Discovery HR-2 Rheometer (TA Instruments). Viscosity measurements were performed to assess formulation structure, consistency, and flow behavior. A commercial benchmark product was evaluated concurrently to compare viscosity profiles and determine the extent to which the bio-based formulations matched or exceeded the performance of conventional market-leading topical creams.

Assay of active ingredients:

UV-Vis absorbance analysis was performed using a GENESYS 10S UV-Vis Spectrophotometer to detect the presence of the API, lidocaine HCl. Samples of pure lidocaine raw material, the in-house developed cream, and the commercial cream were evaluated by dissolving in acetonitrile, followed by sonication and filtration.

HPLC screening:

Lidocaine 4% as pure raw material in the developed base, the in-house developed cream (4%), and the commercial cream were diluted with MeOH, sonicated, filtered, and analyzed using an Agilent 1100/1200 HPLC system equipped with a Cogent Bidentate C18 column (2.1 × 250 mm, 4 µm). Conditions were as follows: initial flow rate, 0.200 mL/min; column temperature, 50 °C; run time, 16 minutes; gradient mix, 50% deionized (DI) H2O:35% MeOH:15% TEAP; detection, diode array detector (DAD) signals at 262 nm.

Skin hydration testing: A corneometer was used to compare skin hydration values for the V5 formula with those of the commercial formula.

Results

Visual testing: Formulations V1.0–V3.0 exhibited suboptimal sensory and aesthetic attributes. Version 4.0 provided the most favorable combination of appearance, texture, and spreadability, but the addition of vitamin E further enhanced the V5.0 formula, yielding optimal sensory attributes close to those of the benchmark cream.

Viscosity testing: Formulations V1.0–V3.0 exhibited viscosity values above the target range for topical cream formulations. In contrast, formulations V4.0 and V5.0 demonstrated viscosity within the expected range (15,000–50,000 cP), indicating suitable consistency, spreadability, and physical stability. Comparative evaluation of the optimized V5.0 formulation with the commercial benchmark revealed similar rheological behavior, demonstrating that the bio-based excipient system achieved performance comparable to conventional topical cream formulations.

Assay for active ingredient lidocaine:

UV-Vis analysis using a GENESYS 10S spectrophotometer indicated that the spectral profile of V5.0 closely matched those of the lidocaine standard and commercial product, confirming successful API incorporation and formulation compatibility without significant degradation or excipient interference, and supporting comparable formulation performance. UV-Vis analysis of V5.0 confirmed the presence of lidocaine, with characteristic absorbance peaks observed at 210–230 nm and 261–263 nm (Figure 4).

HPLC screening:

HPLC profiles for lidocaine in the raw material, the in-house developed cream, and the commercial cream showed similar AUs at 262 nm, indicating that the active lidocaine was released from the excipients as expected and similarly to the pure raw material and the commercial cream. All 3 showed elution times of approximately 7.2 to 7.5 minutes (Figure 5).

Skin hydration testing: Because the in-house developed cream is oil based, hydration values were well above the expected values compared with base skin and comparable to the commercial cream (Figure 6).

Conclusion

The optimized V5.0 lidocaine cream successfully combined effective topical drug delivery with favorable rheological, sensory, and stability characteristics through the incorporation of naturally derived excipients, including starch, sorbitol, coconut oil, and beeswax. These bio-based materials functioned effectively as rheology modifiers, humectants, emollients, and structuring agents, contributing to product stability, consumer acceptability, and overall formulation performance. The formulation exhibited viscosity and flow characteristics comparable to those of a commercial topical analgesic benchmark, demonstrating the suitability of renewable excipients as functional alternatives to conventional synthetic materials.

UV-Vis spectroscopy confirmed the presence of lidocaine and demonstrated absorbance profiles comparable to the reference product. HPLC analysis further verified successful incorporation and stability of the API, with lidocaine identity confirmed by retention time matching to a certified reference standard.

The selected bio-based excipients were readily available, cost-effective, and aligned with sustainable formulation principles. Their use reduced dependence on petroleum-derived excipients while maintaining critical quality attributes of the finished product. In addition, naturally derived excipients may provide an alternative formulation approach for consumers seeking products with reduced synthetic excipient content.

Although botanical actives such as turmeric extract (Curcuma longa), calendula extract (Calendula officinalis), and arnica extract (Arnica montana) possess reported wound-healing and anti-inflammatory properties, formulation and stability challenges precluded their inclusion in the final optimized formulation. These ingredients remain promising candidates for future investigation as complementary bioactive components in sustainable topical systems.

Overall, this study demonstrates the feasibility of developing a sustainable topical analgesic formulation using renewable, bio-based excipients without compromising product quality, stability, or functionality. The optimized formulation achieved performance comparable to commercially available products formulated with synthetic excipients, supporting the application of green chemistry principles in topical product development.

Study Limitations

This study was limited to laboratory-scale formulation development and characterization. Long-term stability, skin permeation, clinical efficacy, scale-up feasibility, and quantitative sustainability assessments were not evaluated. Additionally, formulation and stability challenges prevented incorporation of botanical actives into the final formulation.

Future Work

Future studies should assess long-term stability, skin permeation, clinical performance, and manufacturing scalability. Further optimization may enable incorporation of botanical actives such as Arnica montana, Calendula officinalis, and Curcuma longa, while life-cycle and environmental impact assessments could further quantify the sustainability benefits of bio-based excipients.

References

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