Herbal Effervescent Tablet for Stress Management: Development and Characterization

INTRODUCTION

World Health Organization has given “Mental Health Action Plan (mhGAP) for the period of 2013–2030,” in which mentioned the role of mental health for achieving all people’s health. According to the summary of this plan, there are 4 major objectives like, Strength and effective leadership for governing mental health; Provision of comprehensive, integrated and responsive mental health as well as and social care to all communities; Implementation of strategies for promotion of mental health; Provision of strong informative systems, evidence and research for mental health (Anonymous, 1976). Similarly, to that, Institute of Health Metrics and Evaluation (2022) has published “the fact sheet,” which was focused on mental disorders. This was based on description given by the International Classification of Diseases in 11^th revised volume (ICD-11). This fact sheet had mentioned many mental diseases or illness like, in 2019, 1 person out of 8 people, or approximate 970 million people around the world were living with a mental disorders like anxiety and depressive disorders (Charlson et al., 2019). In 2020, it was mentioned that these anxiety and depressive disorders are because of the COVID-19 pandemic. Though, initially estimated 26%, but later on in 2022, it was increased 28% for anxiety and major depressive disorders.

In 2019, 301 million people includes 58 million children and adolescents were living with an anxiety disorder. Similarly, in 2019, 280 million people includes 23 million children and adolescents were living with depression, in 2019, 40 million people suffered with bipolar disorder. Schizophrenia had affected approximately 24 million people or 1 person out of 300 people worldwide (CCRAS, 2018). In 2019, 14 million people includes almost 3 million children and adolescents had experienced eating disorders. In 2019, 40 million people includes children and adolescents were living with conduct-dissocial disorder, neurodevelopmental disorders, behavioral and cognitive disorders. Above-mentioned disorders were raised during the developmental period and because of that significant difficulties were observed in the acquisition and execution of specific intellectual, motor, language or social functions. It leads the disorders like intellectual development, autism spectrum disorder, attention deficit hyperactivity disorder and so on. Charlson et al. (2019) had also cited that the prevalence of Post-Traumatic Stress Disorder and other mental disorders was high due to conflict affected settings (Institute of Health Metrics and Evaluation, 2022).

Based on this serious concern for mental health, the research work was selected for relaxation in mental disorders. As per the literature survey on antistress plants, we have selected Tagar (Valeriana wallichi; Family: Valerianaceae) and Jatamansi (Nardostachys jatamansi; Family: Caprifoliaceae) for its highly promising nervine tonic activities. So, the described plants were selected to formulate “stress reliever” herbal and novel product (Jamal et al., 2022).

MATERIALS AND METHODS

Materials

The materials used for the formulation of herbal effervescent tablets included Tagar extract (Valeriana wallichii) and Jatamasi extract (N. jatamansi) as the active pharmaceutical ingredients. These herbal extracts were selected based on their reported antistress and neuroprotective properties. The excipients employed in the formulation comprised citric acid, sodium carbonate, sodium bicarbonate, povidone, simethicone, polyethylene glycol, flavoring agent, and purified water. Citric acid and sodium bicarbonate served as effervescent agents responsible for carbon dioxide generation upon contact with water, while povidone was used as a binder to improve tablet integrity. Polyethylene glycol acted as a processing aid, and simethicone was incorporated to reduce excessive foaming during tablet dispersion. The flavoring agent was added to enhance palatability and patient acceptability. All pharmaceutical excipients complied with the specifications of the Indian Pharmacopoeia, whereas the flavoring agent conformed to Food Safety and Standards Authority of India requirements. The selected materials were considered suitable for the development of a stable, effective, and patient-friendly herbal effervescent dosage form (“Mental health and COVID-19”, 2022).

Methods

Selection of Plant materials for its Antistress activities

Two medicinal plants, V. wallichii and N. jatamansi, were selected for evaluating antistress activity based on their traditional therapeutic use and reported pharmacological properties. Valeriana wallichii (Family: Valerianaceae), commonly known as Indian valerian, Muskroot, or Tagar, was utilized in the form of a root extract prepared from its rhizome and root parts. Similarly, N. jatamansi (Family: Caprifoliaceae), commonly known as Tapaswani, was selected, and its root extract was used for the study. Both plants have been extensively employed in traditional medicine systems for their calming, adaptogenic, neuroprotective, and stress-relieving effects, making them promising candidates for the investigation of antistress potential (Rahman and Muralidharan, 2010). The root extracts were chosen as the sample products because these plant parts are known to contain significant concentrations of bioactive phytoconstituents responsible for their therapeutic activity.

Selection of Dosage form

Day to day focus on development of novel formulations in Nutraceuticals and Herbal medicines for health and wellness. There is a continuous demand in market for convenient and palatable delivery systems of herbal medicines, which have to significantly increase the interest in development of herbal ayurvedic effervescent tablet as an alternate to conventional dosage forms. Effervescent tablet formulations are convenient and easily applied method with herbal extracts. The advantages of effervescent tablets are like its rapid disintegration of tablet, formation of a palatable and refreshing solution after mixing with saliva, better drug absorption due to releasing of carbon dioxide, these type tablets are formulated with a mixture of acids and bases, which reacts in the presence of water and production of carbon dioxide gas, which leads to rapid dissolution of the active ingredients, not required to swallow tablet, with prompt and fast onset of actions, always good for stomach and intestinal tolerance, more portability, with accurate dosing and useful to improve therapeutic effects. With focus on above-mentioned advantages, the herbal extracts were selected for the formulation of effervescent tablet as a part of research. Figure 1 shows step-by-step procedure of effervescent tablet while Figure 2 shows picture of effervescent tablet. Table 1 shows the result of trial herbal effervescent tablets formulation.

Click to enlarge

Click to enlarge

Evaluation of Prepared Tablet

Evaluation of Herbal Effervescent Tablets

The prepared herbal effervescent tablets were evaluated for their physico-chemical and performance characteristics according to standard pharmacopeial procedures. Tablet appearance, color, odor, and surface texture were visually examined. Weight variation was determined by individually weighing 20 tablets and calculating the average weight and percentage deviation. Tablet hardness was measured using a hardness tester and expressed in kg/cm². Friability was assessed using a Roche friabilator operated at 25 r.p.m. for 4 min, and the percentage weight loss was calculated. Tablet thickness and diameter were measured using a digital vernier caliper (“Mental health and COVID-19”, 2022).

The effervescent properties were evaluated by determining the effervescence time and dispersion time. Effervescence time was recorded as the time required for complete cessation of carbon dioxide evolution when a tablet was placed in a specified volume of water at room temperature. The pH of the resulting solution was measured using a calibrated digital pH meter. Moisture content was determined to assess the stability of the formulation (Rahman and Muralidharan, 2010). Drug content or herbal extract content uniformity was evaluated by appropriate analytic methods to ensure uniform distribution of active ingredients. Additionally, organoleptic properties, including taste and mouthfeel of the reconstituted solution, were assessed to determine patient acceptability. The optimized formulation was selected based on satisfactory mechanical strength, rapid effervescence, acceptable pH, content uniformity, and overall stability (“The Ayurvedic Pharmacopoeia of India (API) (2000; 2003; 2007; 2008): Appendix part-II”, n.d.).

Stability Study

As per the Accelerated stability protocol, effervescent tablet was kept in stability chamber at 40°C±2 and 75±5% relative humidity. Packed, intact with complete label were kept in stability chamber (“The Ayurvedic Pharmacopoeia of India (API)”, 2008). Total storage period in stability chamber for accelerated stability was continued up to 6 months and time to time analysis were done at 0, 3, 6 months, with prescribed parameters as per CCRAS guideline and Ayurvedic Pharmacopoeia of India (API). The compiled data were collected and compared. The results were interpreted like, variation should not be more than 25%. Once product complies, then the expiry period or shelf life can be claimed for 24–36 months (“The Ayurvedic Pharmacopoeia of India (API)”, 2008).

As per the Real time stability protocol, effervescent tablet was kept ambient room temperature. Samples must be packed and intact with complete label. Total storage period for Real time stability was continued up to 6 months and time to time analysis were done at 0, 1, 6 months, with prescribed parameters as per ICH guideline and prescribed parameters by CCRAS (“The Ayurvedic Pharmacopoeia of India (API)”, 2008–16).

RESULTS AND DISCUSSION

Certified Plant Raw Materials Extracts of Tagar and Valleriana Was Procured from Konark Herbals and Healthcare

As per Certificate of Analysis of Jatamansi dry extract, physico-chemical parameters of identification, loss on drying, pH of 1% solution, water soluble extractive, and Assay of Jatamansone by gravimetric method were within the limit. Heavy metals (lead, cadmium, mercury and arsenic) were compiled within specification limit of API. Microbiological analysis like total bacterial count, total fungal count and qualitative performance of pathogens like Escherichia coli, Salmonella ssp., Staphylococcus ssp., Pseudomonas ssp. Were within the specification limit of API.

With these results of herbal extract, the literature was surveyed and studied the following research paper by Rehman and Murlidharan (2010). They had studied antidepressant activity of methanolic extract of N. Jatamansi applying and measuring by forced swim test, tail suspension test and locomotors activity in inbred male Swiss mice. They had proved efficacy of extract with the dose of 200 and 400 mg kg⁻¹ p.o., which was compared against the standard drug that is, imipramine, 10 mg kg⁻¹ in normal and sleep deprived mice. The results showed that N. jatamansi extract at the dose of 200 and 400 mg kg⁻¹ p.o. produced significant changes in locomotor functions of mice as compared to normal control. However, it was significantly (p<0.01) improving the locomotors activity in case of sleep deprivation which is comparable to normal control. They concluded that N. jatamansi had dose dependent antidepressant activity and can also be used in patients suffering from depression due to sleep disturbances (“The Ayurvedic Pharmacopoeia of India (API)”, 2008).

As per Certificate of Analysis of Tagar dry extract, physico-chemical parameters of identification, loss on drying, pH of 1% solution, water soluble extractive, and Assay of valeric acid by titrimetric method were within the limit. Heavy metals (lead, cadmium, mercury and arsenic) were compiled within specification limit of API. Microbiological analysis like total bacterial count, total fungal count and qualitative performance of pathogens like E. coli, Salmonella ssp., Staphylococcus ssp., Pseudomonas ssp. Were within the specification limit of API. Based on these results, the similar research paper was studied for the chemical constituents of V. wallichi and its properties by Jamal et al. (2022) (“The Ayurvedic Pharmacopoeia of India (API)”, 2008).

Stability Study (Accelerated and Real Time)

Both Stability study of herbal effervescent tablet was performed at Altra analytic laboratories (AYUSH approved, license no. GATL/04), Ahmedabad, Gujarat.

As per the Accelerated stability protocol (API, 2000–2016), effervescent tablet was kept in stability chamber at 40°C±2 and 75±5 relative humidity. Packed, intact with complete label were kept in stability chamber. Total storage period in stability chamber for accelerated stability was continued up to 6 months and time to time analysis were done at 0, 3, 6 months, with prescribed parameters as per CCRAS guideline (2018) and API. The compiled data were collected and compared that results variation was not more than 25%. So, the product was compiled the accelerated stability, means the expiry period or shelf life shall be claimed for 24–36 months. Table 2 shows the results of evaluation of Herbal Effervescent tablet by Accelerated Stability (“The Ayurvedic Pharmacopoeia of India (API)”, 2008).

As per the Real time stability protocol, effervescent tablet was kept ambient room temperature. Samples were packed and intact with complete label. Total storage period for Real time stability was continued up to 6 months and time to time analysis were done at 0, 1, 6 months, with prescribed parameters as per ICH guideline and prescribed parameters by CCRAS. The compiled data were collected and compared that results variation was nor more than 25%. So, the product was compiled the accelerated stability, means the expiry period or shelf life shall be claimed for 24–36 months. Table 3 shows evaluation of Herbal Effervescent tablet by Real Time Stability.

High-Performance Liquid Chromatography (HPLC) Study

Ingredients percentage were considered against 100% of Standard. Both extracts/ingredients are water soluble and detected/absorbed at same wavelength (254 nm). So, significant with product absorption wavelength (254 nm). Proportion ratio in product was Ratio 11: 9 (Tagar; Jatamansi). Table 4 shows HPLC results of Ingredients’ availability in Effervescent Tablet. Figures 3a and 3b shows the HPLC Chromatogram of Tagar extract as standard and HPLC Chromatogram of Jatamansi extract as standard. While Figures 4a and 4b, shows Chromatogram of Tagar extract in Effervescent Tablet and Chromatogram of Jatamansi extract in Effervescent Tablet. The HPLC analysis of the herbal effervescent tablet demonstrated satisfactory incorporation of both Tagar and Jatamansi extracts. Tagar extract showed a peak area of 149.6233 at 254 nm, while the corresponding effervescent tablet exhibited a peak area of 162.2366, indicating an ingredient concentration of 1,084.30 parts per million and an absorption value of 108.43%. Similarly, Jatamansi extract displayed a peak area of 173.2390 at 254 nm, whereas the effervescent tablet showed a peak area of 158.1263, corresponding to an ingredient concentration of 912.76 parts per million and an absorption value of 91.28%. These results confirm the successful incorporation and acceptable recovery of both herbal constituents within the formulated effervescent tablets, indicating good content uniformity and formulation integrity.

Click to enlarge

Click to enlarge

Click to enlarge

Click to enlarge

CONCLUSION

With the above study, we can conclude that the results may vary from batch to batch and/or lot to lot. The quality parameter testing is important attribute to cater the better products to the society. Once quality parameters are defined and results are within the specifications, we may conclude that products shall be promising and effective for stress management. The formulation demonstrated acceptable physico-chemical properties, rapid effervescence, and satisfactory stability under accelerated storage conditions. HPLC analysis confirmed the presence and adequate recovery of the active herbal constituents, indicating good content uniformity and formulation integrity. The accelerated stability study showed that the product remained stable in HDPE packaging under prescribed conditions. Overall, the developed herbal effervescent tablet represents a promising, patient-friendly dosage form with potential therapeutic benefits and enhanced convenience, warranting further clinical evaluation.

ACKNOWLEDGEMENT

We are thankful to Konark Herbals and Healthcare for providing us certified raw materials. Also thankful to Hetal Pharmaceuticals, Gujarat for formulating novel products from initial to final finished goods and thankful to Altra Analytical Laboratories, Ahmedabad for performing the stability studies.

ABBREVIATIONS

HPLC

High-Performance Liquid Chromatography

API

Ayurvedic Pharmacopoeia of India

ICH

International Council for Harmonisation

CCRAS

Central Council for Research in Ayurvedic Sciences

WHO

World Health Organization

HDPE

High-Density Polyethylene

ICD-11

International Classification of Diseases, 11^th Revision

mhGAP

Mental Health Action Plan

GHDx

Global Health Data Exchange

QS

Quantum Satis.

CONFLICT OF INTEREST

The authors declare that there is no conflict of interest.