Development of a Herbal Cream Formulation from Ya Ha Rak Extract

Abstract

Introduction and Objectives: The "Ya Ha Rak", an oral traditional Thai herbal formula for treating fever, has officially been listed in the National List of Essential Herbal Medicines since 1999. It consists of the roots of five medicinal plants: chingchi (Capparis micracantha DC.), Ya Nang (Tiliacora triandra (Colebr.) Diels), Khontha (Harrisonia perforata (Blanco) Merr.), Tao Yai Mom (Clerodendrum indicum (L.) Kuntze) and Ma Duea U Thum Phon (Ficus racemosa L.). Investigations into biological activity studies revealed that Ya Ha Rak exhibits anti-allergic activity through the inhibition of immune reactions, melanogenesis and tyrosinase inhibition, as well as antioxidant activity. No skin irritation was observed in human skin, indicating that the formula is safe for topical application. Therefore, it has the potential to be used externally for the treatment of allergic dermatitis. This study aimed to develop a cream formulation incorporated with Ya Ha Rak spray-dried extract and to establish an analytical method for quality control, including the evaluation of the chemical and physical stability of the cream formulation.

Methods: The dried Ya Ha Rak herbal formula extract was prepared by aqueous decoction extraction followed by spray drying. Subsequently, an analytical method employing reversed-phase high-performance liquid chromatography (RP-HPLC) was developed for the quantification of the marker compound, perforatic acid, to ensure the quality control of the obtained extract. The method was further validated by ICH Q2(R1) guidelines. Then, the obtained extract was formulated into an oil-in-water cream. The physical characteristics, the amount of perforatic acid within the cream formulation, and the functional properties of each formula were evaluated to select the most suitable formulation. Finally, the stability study of the chosen cream product was conducted by the ASEAN Guidelines for the Stability Study of Drug Products (2013) under two conditions: room temperature (30 ± 2°C, without controlled relative humidity) and accelerated condition (40 ± 2°C, 75 ± 5% relative humidity) for 6 months, with subsequent estimation of the product shelf life.

Results: The Ya Ha Rak extract obtained from spray drying exhibited a herb-to-dry extract weight ratio of 7.3:1. The method validation yielded the following results. The specificity of the analytical method was evidenced by the purity of the perforatic acid peak in the chromatogram of Ya Ha Rak extract. The calibration curve for perforatic acid was linear over the concentration range of 8.68-79.0 µg/mL, with r² of 0.9997. The relative standard deviation (RSD) for repeatability was within 2%. The percentage recovery ranged from 98.0% and 102.0%. The limit of quantitation (LOQ) and limit of detection (LOD) were determined to be 0.34 µg/mL and 0.07 µg/mL, respectively. The development of cream formulations revealed that Formulation 3, comprising 67% purified water, 10% propylene glycol, 6.5% liquid paraffin, 5% cetyl alcohol, 4.5% Lexemul^® 561, 4% stearyl alcohol, 2.5% Ya Ha Rak extract, and 0.5% Spectrastat BHL^TM by weight, exhibited superior physical characteristics, including a smooth, homogeneous texture without phase separation, a mild herbal scent, and a pleasant skin feel. The formulation complied with the quality control criteria specified in the pharmacopoeia. The content of perforatic acid found was determined to be 1.38% w/w in the extract and 32.52 mg per 100 g of cream formulation. A six-month stability study demonstrated that the cream formulation exhibited physical and chemical stability under both accelerated and room-temperature storage conditions. The estimated shelf life of the product was determined to be 25 months.

Discussion: The extraction method employed Thai traditional medicine practices by using water decoction followed by spray drying, which effectively preserves the quality of the extract by minimizing thermal degradation. The quantitative analysis of perforatic acid using RP-HPLC was developed and validated following ICH Q2(R1) guidelines, ensuring accurate quality control of both the extract and cream formulations. For the cream development using 2.5% w/w concentration of the herbal extract, formulation 3 exhibited the most favourable properties, including a smooth texture, pH of 4.93 ± 0.03, and viscosity of 65,848 ± 2,463 cP. The perforatic acid content was found to be 32.52 mg per 100 g of cream. Stability studies conducted over 180 days under both room temperature and accelerated conditions demonstrated excellent stability in physical appearance, viscosity, and active compound content, with the percentage reduction in perforatic acid not exceeding 2.1%. These results indicate that the developed formulation possesses adequate stability and quality for further clinical investigation.

Conclusion and Recommendation: The developed Ya Ha Rak cream formulation demonstrated suitable physical characteristics, satisfactory stability, and complied with the quality standards in the pharmacopoeia. It is recommended that further in vivo studies, particularly in human subjects be conducted to assess the efficacy and safety of the formulation for the treatment of allergic dermatitis.